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Medifocus Guidebook on Peripheral Neuropathy

2011-07-15T05:54:00.001-07:00

What is Peripheral Neuropathy?
The nervous system controls the smooth functioning of all systems in the body as well as all interactions between the human being and the environment. The nervous system is comprised of millions of neurons that are interconnected and form a communications network within the body that governs many vital functions including:

The five senses (sight, hearing, touch, smell, and taste)
Voluntary functions (e.g. walking, holding an object)
Involuntary functions (e.g. breathing, blood pressure)
Cognitive reasoning

The human nervous system has two major components:

Central nervous system - includes the brain and spinal cord
Peripheral nervous system - includes the nerves that lead from the brain and spinal cord to all parts of the body. An extensive system of specialized nerves makes up the peripheral nervous system which is responsible for a variety of important functions. These specialized nerves include:
- motor nerves which carry messages from the brain to the body and are responsible for the ability to move any part of the body (e.g., hands, feet)
- sensory nerves which carry information from organs to the central nervous system where it is processed into sensation (e.g., touch, temperature changes, and vibrations)
- nerves that control autonomic (involuntary) functions including heart rate, blood pressure, breathing, digestion, and bladder function

Peripheral neuropathy is a term used to describe damage to nerves of the peripheral nervous system which leads to symptoms such as pain, numbness, tingling, burning, and weakness most commonly affecting the hands and feet. Peripheral neuropathy can be caused by a variety of precipitating factors including trauma, infection, diabetes, alcohol abuse, and cancer chemotherapy.
The incidence of peripheral neuropathy is not known with any degree of certainty. It has been estimated that approximately 2 to 3 million Americans have some form of peripheral neuropathy. The prevalence of peripheral neuropathy worldwide has been estimated to range from 2% to 8% of the population. Peripheral neuropathy affects both genders at all ages but symptoms are unique to each individual in terms of frequency, quality, and severity of pain. Idiopathic peripheral neuropathy typically affects adults over the age of 50. Peripheral neuropathy can significantly impact an individual's quality of life and daily activities by causing major disruptions including:

Sleep disturbances
Mood changes
Impairment of social, occupational, and recreational functioning

Knowledge is Critical when Dealing with a Life-Altering Condition such as Peripheral Neuropathy
If you or a loved one has been diagnosed with peripheral neuropathy, it's critical to learn everything you possibly can about this condition so that you can make informed decisions about your treatment. That's why we created the Medifocus Guidebook on Peripheral Neuropathy, a comprehensive 187 page patient Guidebook that contains vital information about peripheral neuropathy that you won't find anywhere in a single source.
The Medifocus Guidebook on Peripheral Neuropathy starts out with a detailed overview of the condition and quickly imparts fundamentally important information about peripheral neuropathy, including:

The underlying causes and risk factors for developing peripheral neuropathy, which include:
- Diabetes
- Autoimmune disorders
- Metabolic disorders
- Hereditary disorders
- Infectious diseases
- Alcohol abuse
- Trauma
- Cancer chemotherapy
The different types of peripheral neuropathy that can occur based on the pattern of nerve involvement and the distribution of pain, which include:
- Mononeuropathy
- Mononeuropathy multiplex
- Polyneuropathy
The signs and symptoms associated with peripheral neuropathy based on the specific underlying cause, when known.
How peripheral neuropathy is diagnosed based on a variety of factors and diagnostic tests including:
- Signs and symptoms
- Patient history and physical examination
- Pattern of distribution of pain along sensory or motor nerves
- Special electrodiagnostic studies, such as nerve conduction tests and electromyography (a test which measures the response of muscles to electrical stimulation)

Understanding the Standard Treatments...and the Treatment Options
The primary goals of treatment for peripheral neuropathy include accomplishing the following objectives:

Determining and treating the underlying cause of the condition, if possible.
Controlling and alleviating pain and other bothersome symptoms associated with the condition.
Preserving function of the affected limbs, such as the hands and/or feet.
Preventing a significant decrease in the patient's quality of life.

An important aspect for successfully achieving these goals is understanding the treatments - and the treatment options - for peripheral neuropathy. As you read through the section of the Guidebook that focuses on the treatment of peripheral neuropathy, you will specifically learn about:

The management of peripheral neuropathy in patients where the underlying cause can be identified, such as diabetes, autoimmune disorders, infectious diseases, nerve compression, and cancer chemotherapy.
The major types of medications that are often prescribed to relieve pain associated with peripheral neuropathy, which include:
- Antidepressants
- Anticonvulsants
- Selective serotonin reuptake inhibitors
- Narcotic analgesics
- Topical agents such as capsaicin and lidocaine patches
The treatment options that are available for controlling pain that does not adequately respond to drug therapy, including nerve blocks with local anesthetics and spinal cord stimulation.
The role of physical and occupational therapy in functional rehabilitation of patients with peripheral neuropathy.
The role of complementary and alternative therapies in the management of peripheral neuropathy.
The impact of peripheral neuropathy on the patient's psychological well-being and quality of life, including aspects such as:
- Anxiety and depression
- Social relationships
- Activities of daily living
- Employment issues
- Sleep disturbances
- Recreational activities
- Feelings of self-worth
Practical tips and suggestions for how to minimize the negative impact of peripheral neuropathy on your quality of life and learn how to better cope with the condition.
Important questions to ask your doctor about peripheral neuropathy.

A "One-of-a-Kind" Reference Guidebook on Peripheral Neuropathy that Goes Way Beyond the Fundamentals
Since 1996, when Medifocus was founded, we've learned that many people with Peripheral Neuropathy are seeking more specific information that goes beyond the fundamentals, such as the causes, diagnosis, standard treatments, and treatment options. That's why we developed a "one-of-a-kind" reference Guidebook that goes way beyond the basics and also includes the following sections:

A Guide to Recent Medical Literature on Peripheral Neuropathy - This section of the Guidebook contains an extensive bibliography of over 100 references to recently published articles about Peripheral Neuropathy in authoritative, peer-reviewed medical journals with links to the absracts (summaries) of the articles. These articles represent the latest advances in the field and focus on cutting-edge research, new developments, and the lessons learned from recently published clinical trials involving patients with Peripheral Neuropathy. This is the same level of that is used by doctors who treat people with Peripheral Neuropathy to keep abreast of the latest developments and breakthroughs in this specialized field of medicine.
Centers of Research for Peripheral Neuropathy - We've compiled a unique directory of doctors, hospitals, medical centers, and research institutions with special interest and, in many cases, clinical expertise in managing people with Peripheral Neuropathy. The "Centers of Research" directory is a valuable resource for quickly identifying and locating leading medical authorities and medical institutions both within the United States and other countries who are considered to be at the forefront in clinical research and treatment of Peripheral Neuropathy. You'd have to spend days - or even weeks - attempting to compile your own list of doctors and medical centers but, with the "Centers of Research" directory, the information is already right at your fingertips. All you have to do is act on the information by selecting and contacting the experts or medical institutions listed in the directory by state and country.
Organizations and Support Groups for Peripheral Neuropathy - The Guidebook also includes a directory of organizations and support groups whose goal is to help people with Peripheral Neuropathy by providing access to information, resources, and services. Many of these organizations can answer your specific questions, enable you to "network" with other patients, and provide guidance in areas such as financial, social, or medical-legal issues. This valuable directory of organizations and support groups includes complete contact information, including phone numbers and E-mail addresses.

The Guidebook is a Value-Added Proposition that Comes with a Risk-Free Satisfaction Guarantee so that...You have Nothing to Lose and Everything to Gain
Still not sure if you'll benefit from the Medifocus Guidebook on Peripheral Neuropathy? Still not convinced that the information included in the Guidebook is worth the minimal cost? If that's the case, then please consider the following value-added proposition that comes standard with your purchase of the Guidebook:

Free Updates for One Year - With your initial purchase of the Guidebook, you also receive access to free updates for one-full year. The Guidebook is updated with new information every 4 to 6 months, so that you will be able to access the updated information several times during the course of a year for up to one full year after the date of your initial purchase.
Free Digest E-Mail Alerts - When you purchase the Guidebook, you will also automatically receive a free subscription to our monthly newsletter - the Medifocus Digest Alert for Peripheral Neuropathy. This is an expertly selected listing of the latest articles published in the medical literature about Peripheral Neuropathy with convenient links to the abstracts of the articles that focus on cutting-edge research, clinical trials, and the latest treatment advances. The Medifocus Digest Alert for Peripheral Neuropathy is automatically delivered straight to your "inbox" monthly and is a valuable resource for keeping up with the latest developments in Peripheral Neuropathy almost as soon as the new information is published in the medical literature.
10% Discount - For a limited time, you can purchase the Medifocus Guidebook on Peripheral Neuropathy at a special 10% discount off the regular list price. Your 10% discount will automatically be applied when you go to "Checkout".
Risk-Free Satisfaction Guarantee - Your purchase comes with our RISK-FREE satisfaction guarantee. If, for whatever reason, you are not totally satisfied with the content of your Guidebook, simply contact us within 30-days of your purchase for a prompt, full refund. We are so confident that you will be satisfied with your Guidebook that we offer this RISK-FREE satisfaction guarantee unconditionally - no questions and no hassles

Doctor Says Surgery May Relieve Pain Of Neuropathy

2011-07-15T05:52:00.001-07:00

DENVER -- Millions of Americans suffer from neuropathy, a painful condition that affects legs and feet. For many, medication is the only relief, but that can stop working.
Now a doctor in Colorado is one of just a few surgeons in the country offering another alternative.Gregory Garland says he has a tremendous amount of pain in his foot and leg and is going under the knife to treat it.

"I'm having the tunnels opened up around the nerves in my feet," Garland said.Dr. James Anderson of the Poudre Valley Foot and Ankle Clinic is one a very few surgeons doing a new controversial procedure for people who suffer from neuropathy."Neuropathy is basically a malfunction of nerves. You'll get burning, tingling and numbness. The pain is not sometimes bad in the beginning but it can become very severe," Anderson said.Neuropathy is common in diabetics and is the leading cause for amputations. Until now, there was little that could be done for patients.This new surgery is similar to that commonly done for carpal tunnel syndrome in the wrist."It's a decompression surgery," Anderson said.The tight areas are opened in up in the ankle, giving the nerves more room to pass."If you can release pressure from the nerves, the neuropathy symptoms can go away," Anderson said. "It's like restoring the nerves, basically."Before surgery is considered, the patient undergoes numerous tests. Surgery is not for everyone and recovery can take several months.But many patients are getting permanent relief.Dick O'Grady had the surgery 10 months ago. Before that, his life basically came to a standstill, he said."The pain became so intense that I went into the emergency room and was in the hospital for four days," he said.Now, he can do the things he loves such as working in his yard without pain. "I really feel like a success story," O'Grady said. "To this day I have absolutely no regrets. I am getting my life back and becoming more mobile. I am sleeping at night now without the pain.""We are right at about 85 percent success rate," Anderson said.Currently, the prevailing theory is there is no cure for neuropathy and some doctors adamantly discourage patients from having this surgery. It's important to discuss all the options with your own doctor.If you would like more information on the decompression surgery for neuropathy call (800) 866-4620 or go to .

Nitrogesic

2011-07-15T05:51:00.002-07:00

Nitrogesic Descriptions

Many people are suffering from anal fissure, which is a crack or tear in the skin of the anal canal. However, anal fissures may cause painful bowel movements and bleeding as well. There may be blood on the outside of the stool or in the toilet following a bowel movement. Hence proper hygienic measures should be taken with the usage of the best medicine. Nitrogesic ointment is widely used to treat anal fissures.

Glyceryl trinitrate belongs to the class of muscle relaxants. It is an organic nitrate that donates nitric oxide. Nitroglycerin relaxes the anal sphincter muscle and provides immediate symptomatic relief in pain and spasm. To avoid surgery Nitroglycerin ointment is an ideal treatment for anal fissure. It is also used to treat hemorrhoids.

Before applying the Nitroglycerin ointment i.e. Glyceryl trinitrate ointment, please ask your doctor or for a copy of the manufacturer’s information for the patient and read it carefully. Talk to your doctor about the risks of applying Nitrogesic ointment. Do not let anyone else take your medication especially a woman who is or may become pregnant.


	How To Use Nitrogesic Use this ointment exactly as prescribed by your health care professional. Moreover, do not rub the Nitrogesic ointment onto the skin harshly. However, if you wish to use the medication for your children, please contact your pediatrician.

Nitrogesic side effects

If you notice any of the symptoms, which seem severe or persistent to you, please contact your doctor immediately. The symptoms may be – blurred vision, headache, a feeling of extreme pressure in the head, sweating, nausea, vomiting, dry mouth, skin irritation from application of the ointment, flushing of the face or neck, palpitations i.e. irregular heartbeats, unusual weakness and tiredness, swelling on face, tongue, lips, skin hives, itching, rashes etc.

Inform your doctor if you experience any of these side effects and if they appear too bothersome to you.

Nitrogesic interaction

Inform your doctor if you are allergic to the formulation of this medication or any other medication in any other form and also inform your doctor about any other medication you may be taking in any other form.

Nitrogesic may interact with the heparin, alteplase, foods, varied medications, aspirin medication for mental depression like phenothiazines, chlorpromazine, mesoridazine, prochlorperazine, thioridazine, medication for high blood pressure, medicines for treatment of erectile dysfunctions like Sildenafil, Tadalafil, and Vardenafil, certain migraine medicines like ergotamine or DHE, other medication used to treat angina etc.

Hence, it is necessary to take proper precautions to avoid any reactions.


	Nitrogesic Over Dose In case of overdose call your local poison control center at 1-800-222-1222. If the suffering patient has collapsed or is not breathing call local emergency services at 911. Canadian residents should call their local poison control center directly.

Nitrogesic notes

Do not allow any other person to use your medication without getting doctor’s prescription themselves and also avoid using this medicine for other health conditions on your own.

It is essential to inform your doctor if you have or have ever had diseases like: liver disease, anemia, previous heart attack, bleeding in the brain, head injury, recent stroke etc. Avoid alcohol during the complete course. Keep the medicine away from the children and pets.


	Nitrogesic missed dose If you miss an application of this medicine, apply it as soon as you remember. And, if it is almost the time of your next application, skip the missed application and continue to your regular dosing. Do not double your applications in any case and consult your doctor for the missed application.


	Nitrogesic uses Ideally, Nitroglycerin ointment is used in the treatment for anal fissure as one can avoid surgery. However, Nitroglycerin relaxes the anal sphincter muscle and provides immediate symptomatic relief in pain and spasm. However, it may also be used to treat some other medical conditions which may be determined by your doctor accordingly.


	Nitrogesic other uses This medication may be prescribed for other uses also, so ask your doctor or pharmacist for more information about the Nitrogesic medication. Sometimes, the Nitrogesic ointment is used to treat chest pains.


	Nitrogesic storage Nitrogesic medication should be stored at 15-30°C and 59-86°F and at cool and dry place. Check Expiry date without fail. Keep all medicines away from women, newborns, children and pets. Also, keep it away from heat, dampness and direct light. In any case, do not store the Nitrogesic ointments in the bathroom.

Nitrogesic precaution

Following precautions must be taken during consuming generic Nitrogesic:

1. It is very important for the patient to know that before using Nitrogesic they must inform their health care professional if you have or have ever had diseases like: liver disease, anemia, previous heart attack, bleeding in the brain, head injury, recent stroke etc.

2. Also acknowledge your doctor if you need to undergo any kind of surgery, including dental surgery or need an x-ray procedure that uses contrast agents. So, inform your doctor immediately about it, so that the doctor can decide whether to continue taking Nitrogesic or stop it during the surgery.

3. Let the doctor also know if you are in-taking or are planning to take any prescribed or non prescribed medicines, health supplements or any OTC medications, vitamins etc.

4. Do not use the Nitrogesic medication, if you have any kind of allergy to it or to any ingredients of it and tell your doctor or pharmacist about the allergy and get treated.

5. Tell your doctor if you are pregnant or breast feeding before taking Nitrogesic Cream medication or it may result in abortion. Hence, inform your doctor immediately when you plan to conceive, or become pregnant during the course.

6. Do not share the drug with others unless they are prescribed by the doctor themselves. And if your symptoms of side effects do not improve in few weeks or if they become worse and bothersome, check these conditions immediately with your doctor.

7. Please, use the medicine in the prescribed amount and do not overdose it or use it for the longer period of time. Do not discontinue on your own and consult your doctor before doing so to avoid further problems.

8. During the complete course, please avoid alcohol and alcohol containing beverages to achieve good results

Buying Medicine Online

2011-07-15T05:51:00.000-07:00

These days, buying prescription drugs from the Internet is easy, but finding a safe source for those medicines is not. More and more people are turning to the Internet for cheaper drugs that are easy to get, but medicines purchased from these Web sites often come with the risk of harming you or your family. Rogue Web sites are all over the Internet selling drugs that are not what they appear to be. These sites may be selling drugs that are counterfeit, contaminated, or otherwise unsafe.
By being informed about the dangers of buying drugs on the Internet you can protect yourself and your family from the risks posed by rogue Web sites. NABP has been working with the state boards of pharmacy since 1999 to combat those sites that put your health and safety at risk. Over the years NABP has seen that the risks of buying from a rogue site don’t stop at the loss of money. Lives have been lost due to people buying medicines from sites that send dangerous drugs without medical oversight that may have been tampered with, expired, or even fake.
Knowing which Web sites are safe and which ones are not can be confusing. To help you make an informed choice, and as part of its mission to protect the public’s health, NABP has reviewed, and continues to review, thousands of Web sites to determine if they maintain safe pharmacy practices. Unfortunately, the majority of Web sites selling prescription drugs do not.
NABP has created two categories to help you make an informed choice:

Recommended Internet Pharmacies: NABP recommends that patients use sites accredited through the VIPPS (Verified Internet Pharmacy Practice Sites) or Vet-VIPPS (Veterinary-Verified Internet Pharmacy Practice Sites) program. These sites have undergone and successfully completed the thorough NABP accreditation process, which includes a thorough review of all policies and procedures as well as an on-site inspection of all facilities used by the site to receive, review, and dispense medicine.
Not Recommended Sites: These Internet drug outlets appear to be out of compliance with state and federal laws or NABP patient safety and pharmacy practice standards.

Buyer Beware! That Web Site Might Not Be What It Seems

Many Web sites selling prescription drugs are unlicensed, operating illegally, or operating from foreign countries where medicines shipped to the United States are unregulated. Thus, there is no way of knowing whether the medicine you receive is contaminated, sub-potent, super-potent, expired, or counterfeit, or whether it has been stored and shipped under proper conditions to maintain its effectiveness.
And that Canadian online pharmacy with the cheaper prices? It may be calling itself a “Canadian pharmacy,” but it may actually obtain its medications from countries in Asia, South America, or Eastern Europe, where quality standards are more lax and counterfeit medications more widespread. While counterfeit medications can surface anywhere, they are significantly more common in developing foreign countries. That is the problem with buying medicine from foreign sources – you never know what you’re getting.
While there are some excellent Canadian Internet pharmacy sites, NABP cannot recommend any Canadian site selling drugs to Americans because Food and Drug Administration (FDA) regulations prohibit this activity. Prescription drugs imported from other countries are not FDA-approved and their safety and effectiveness cannot be ensured because they are outside the legal structure and regulatory resources provided by Congress.

What Are Sites Listed as Not Recommended Doing Wrong?

NABP continually reviews Web sites selling prescription drugs to help you see through rogue sites. Of the nearly 7,000 Internet sites reviewed, NABP found that 96% of the sites fall in the Not Recommended category because they appear to be operating in conflict with pharmacy laws and practice standards. Of the sites reviewed, the most common reasons for sites being included on the Not Recommended list were:

83% do not require a valid prescription
42% offer foreign or non-FDA-approved drugs
55% do not provide a physical address
20% are located outside of the United States and selling drugs illegally to patients in the US

Only 4% of the sites NABP reviewed are potentially legitimate in that they appear to meet pharmacy laws and practice standards, based on information obtained by looking at the Web site. NABP highly recommends that you use only those Internet pharmacies that are VIPPS or Vet-VIPPS accredited. Currently, 39 sites, representing more than 12,000 online pharmacies, have received accreditation.

Cancer, brain

2011-07-15T05:50:00.001-07:00

Cancer, brain: Cancer of the central information processing center of the body. Tumors in the brain can be malignant or benign and can occur at any age. Primary brain tumors initially form in the brain tissue. Secondary brain tumors are cancers that have spread to the brain tissue (metastasized) from elsewhere in the body.

Doctor Says Surgery May Relieve Pain Of Neuropathy

2011-06-15T01:00:00.000-07:00

Howdy Folks:) Sue Relays Asked Me to Post My Results Here

2011-06-15T00:58:00.001-07:00

I got to know Sue when she visited the Colorectal Board - she's been a good friend and terrific supporter to me. And since she does not get over to our side very much anymore, she asked me if I would post my results over here so she could see them. I hope you don't mind.
From Sue:
"Will be waiting to see your results. Will you post on the anal board as well??"
This is a long post but covers the past year of my fight, currently at 7-years, Stage IV.
Grab something to drink and you're welcome to read along with Sue. And maybe Joanne will show up here - I miss her to and met her on the other board when she first got here.
Ok, Sue and everybody here we go!
“SUNDANCE vs CANCER” – The Results Post
Faster than a speeding locomotive – Able to leap tall buildings in a single bound – Look! – Up in the air! – It’s a bird! – It’s a plane! – It’s…..it’s……awww $hit, it’s only Sundance:)
LOL:)
The “Betting Windows” are now officially closed, so I hope you got your wagers down – there was sure plenty of time:)
Well, this is finally the post that I have waited for and waited to write. And also the one that many of you have waited for as well. Almost a year in the making and through it all, it has been a “Watershed Moment” in my journey.
I suppose when I reflect back on it, we could say that it’s the most influential battle of my entire campaign. There was much at stake to be won or lost. It carried huge significance as I motored on toward my 7th year of this incredible saga. And all the time, never knowing exactly which way the battle was going to go. Would I win? Or would I begin to slip?
The stakes we were playing for was my very existence, which I believe we can all agree, is worth playing for. The difference is we had to fight like there was never going to be tomorrow – because that’s always in the cards and is the key component that weighs so heavily on all of our minds.
It’s a funny feeling looking back on this past year. In many ways, it still feels like yesterday – and then on the other side, it seems like a lifetime ago.
Cancer played a dirty little trick on me this time. We know he does not play fair and is a dirty fighter. He used the DaVinci tumors the time before, to lull us into a false sense of complacency while he stealthily hid behind my lungs and gathered his forces, before he could again announce his presence in my body for this last year’s fight.
When I was still in the hospital after this lung surgery, I remember a nurse bringing me my pathology report. Even dazed on morphine and with blurred eyesight, I could still make out the words…”Colorectal Mets to Lung.”
And I remember thinking, “Now, you’ve showed yourself, you SOB!” I sat up in bed and thought, “I’ve got you now.” You’ve just kicked the sleeping dog – you just woke up the Gentle Giant. So, once again, it’s “officially back on.”
Strangely though, I felt some sense of comfort in those words, in the fact that I again knew what I was going back up against….there was no guessing anymore, there it was in the report. It was time once more to “get my mind right to fight.”
Once I found out the surgery did not completely remove the malignant tumors, I knew it was going to a really long and hard road, with no shortcuts. I was going to have to go all in and gut this one out for the long haul, if I was to have a chance at any kind of victory.
You all know there were times when it looked like I was beaten. Down and out for the count is what’s ahead for our good old Sundance, folks were probably thinking – put a fork in him, he’s done. But then again, you don’t know Sundance:)
I’ve always said I may “bend or waver” during the fight, but that I would never “break.”
Maybe that’s not an entirely true statement. Perhaps, it depends on what your definition of “break” is. In fact, Cancer had me beaten and on my knees begging for either “Death or Mercy.” It had me beaten at the time, but not broken for the long haul of the fight.
“The CURE” had me beaten as well this time , but I stayed strong enough to complete the entire protocol “by the numbers.” It was really difficult this time to mentally and physically step through all the obstacles that stood in our way. As I’ve said before, it gets a little harder to keep taking the pounding, the longer you stay in the fight.
The mind and heart are still willing – but the body just doesn’t “bounce” like it used to. I think this is the biggest difference in an old veteran fighter vs the newly diagnosed.
While the surgeries and treatments have compromised our bodies, we learn we must adapt and use our experience and smarts to fight on, instead of relying on a new body that is just starting out.
My medical team continuously put the foot on the gas and we were very aggressive in our treatment plan and there was no time to rest. We relentlessly pursued our target and stayed in the attack mode the entire time.
Oh yes, I can be beaten – I can be hurt – I can bleed – I can hurt – I can suffer. I am just a mortal man, composed of blood & flesh..
However, on the other side of the coin, I can also be tenacious – persistent – stubborn – and relentless in my own pursuit. My horoscope is “Cancer, the Crab.” I’m a “July Baby.”
We’re loveable, friendly, and loyal – but when fuc*ed with, we raise our pinschers and will snap you. We’re a very formidable force to reckon with. When we hit back, it hurts too, just like we were hurt. We only fight when provoked though and let’s face it, Cancer does provoke us, doesn’t it?
Here’s the last topic I wanted to discuss. Let’s talk about our roommate – HOPE.
What an interesting fella’ this guy is, am I right?
He’s very elusive and if we’re not real careful, he can just slip out of our fingertips and just be gone. And when he goes, he’s sometimes hard to find again. And when Hope moves out, Depression can move in – then he invites Despair, Hopelessness and Loneliness to the party, and from there our lives can disappear and become nothing but existence.
And that’s a very bad place to be – especially for too long. I know, because I spent 9-months with all of these guys this year. They are not nice “house guests.” They try to rob you of that thing that we call “Our Lives.”
And then it becomes up to us to take back back what was so wrongly taken from us. Each of us must do that and find a way to get Hope moved back in with us, so we can flourish and feel optimism.
What is my definition of Hope?
I’ve come to think of Hope as that “Intangible element of humanity that we cannot see, but one that we feel.”
It’s the single common denominator that every single one of us has inside. It’s the driving force behind our individualism and more importantly, the one thing that we “Cling To” and “Reach For” in times of dire circumstances that beset each of us, somewhere in our lifetime.
As the old saying goes, “Let’s Keep Hope Alive!”
Hey, let’s go down to ringside right now, looks like Michael Buffer is about to announce “The Decision.” Who came out on top? Sundance or Cancer?
“Ladies and Gentlemen! The Winner by KO and still the Undefeated Cancer Champion of the World, with a 3-0 title defense, is……….your very own…….SUNDANCE! “
LOL:)
And the crowd goes WILD……….:) !!!
For any of you that bet against me…….”Suckerzzzz!” LOL:)
That’s right folks – 3 recurrences Up and 3 recurrences Down – just like in baseball, huh?
We did it again. We knocked Cancer “Back into the Shadows” once more. He’s gone back into hiding, licking his wounds, while I lick mine. But, we got Him down right now. You read the BAD in my other post…….and now for something completely different, here is the GOOD:
1. Colon and Rectum = Clear
2. Liver = Clear
3. Lungs = All Clear:)
Many of you might recall in my Thanksgiving Message to my Cancer, that I said, “I am down right now – but when I get up, I’m coming – and He11 was coming with me.
Well, with Big Billy by my side, we “Huffed and we Puffed”…and we “Blew the Doors to the Gates of He11 Wide Open!”
What looked like a highly improbable, if not impossible mission at the beginning of this fight, has come to a successful conclusion. I know how fortunate I am to be on the “positive side of the ledger” right now. It sure could have gone either way, but somehow we are on top right now.
We’re officially back to “Watching and Waiting.” I’ll talk to NED, if I make it “clean” for 5-years, with no further recurrences….. (June 2016).
So, it does not get much better than this….am I right?
I thought the balloons were supposed to fall out of the ceiling about now? Why isn’t the band playing? Where’s the cake and ice cream? Where is Jennie with my margaritas?
LOL:)
Since I can’t get to any of you right now…we’ll just have to have a “Cyber Celebration!” I need some folks to share in this joy with me. It will mean more if I have all of you around me in the “same room.”
So, what’s next for Sundance?
I’m going to Disneyworld!...................................Not!
I’ll be lucky to get to Chicago for CP9 – with this very meaningful victory, it is my sincerest hope that I can make it there and get some lovin’ from my honeys:)
What’s next is instead of escaping Cancer, I’m going to jump back into the deep end of the pool and go back to the beginning of the journey – first chapter titled “The Diagnosis.”
I want to jump on getting this written now, while the wounds are fresh and the feelings raw. I’m excited about making this a reality – now publishing will be another story – coming to an Amazon Kindle near you?
I’ll close this post with these final thoughts…..
On the day that Donna (Shayenne) aka “My Chicky” passed away, I posted on that thread that Her Lion had roared for the final time.
A beautiful chapter in my life and on this board and a real life story of friendship had come to a tragic and painful end. On this day a part of me died with her –Her Lion was dead and gone, and yet the memories still remained, but were now forever buried deep within the archives of the CSN posts.
This is a day where I wished Chicky were still here with us – certainly a story she would have loved to hear about and rejoice in. I will miss not seeing her post in this thread.
In honor of her memory and to bookmark this momentous occasion, Donna’s Lion “ROARZZZZ” one more time:) Miss you, Chicky.
This one was for myself, but also for the Semi;Colon Nation. I stand before you as a living testimony to what Cancer “Can and Cannot” do to us. It will never be easy, but you too can do this. I’ll stand proudly beside each one of you and be with you for each stop in your journey. Don’t be afraid – get mad – get even – and get out there and fight!
I understand less and less as time goes by – have no idea of why I’m still here after 7 years of battling this stuff. Don’t understand why my friends did not make it, but I am still here. I suppose I’ll never know.
And Cancer may indeed catch me one day – but guess what? It won’t be TODAY!!!
All of you know that Sundance is not the kind of guy that “Goes Quietly into the Night.”
I carry all of your hopes and dreams with me in my heart. I have the deepest respect and admiration for each one of you here – both past and present. You are the finest group of people I know and I’m proud to know you all.
All of you are Winners – and Cancer will never, ever take that away from you! With all of the love I can muster, I thank you for staying with me and you are all in my thoughts, in my heart, and in my dreams. Semi;Colons Rock!
I SALUTE YOU!!!
Craig and Big Billy
“Team Sundance”

Medifocus Guidebook on Peripheral Neuropathy

2011-06-15T00:56:00.001-07:00

The five senses (sight, hearing, touch, smell, and taste)
Voluntary functions (e.g. walking, holding an object)
Involuntary functions (e.g. breathing, blood pressure)
Cognitive reasoning

The human nervous system has two major components:

Central nervous system - includes the brain and spinal cord
Peripheral nervous system - includes the nerves that lead from the brain and spinal cord to all parts of the body. An extensive system of specialized nerves makes up the peripheral nervous system which is responsible for a variety of important functions. These specialized nerves include:
- motor nerves which carry messages from the brain to the body and are responsible for the ability to move any part of the body (e.g., hands, feet)
- sensory nerves which carry information from organs to the central nervous system where it is processed into sensation (e.g., touch, temperature changes, and vibrations)
- nerves that control autonomic (involuntary) functions including heart rate, blood pressure, breathing, digestion, and bladder function

Sleep disturbances
Mood changes
Impairment of social, occupational, and recreational functioning

The underlying causes and risk factors for developing peripheral neuropathy, which include:
- Diabetes
- Autoimmune disorders
- Metabolic disorders
- Hereditary disorders
- Infectious diseases
- Alcohol abuse
- Trauma
- Cancer chemotherapy
The different types of peripheral neuropathy that can occur based on the pattern of nerve involvement and the distribution of pain, which include:
- Mononeuropathy
- Mononeuropathy multiplex
- Polyneuropathy
The signs and symptoms associated with peripheral neuropathy based on the specific underlying cause, when known.
How peripheral neuropathy is diagnosed based on a variety of factors and diagnostic tests including:
- Signs and symptoms
- Patient history and physical examination
- Pattern of distribution of pain along sensory or motor nerves
- Special electrodiagnostic studies, such as nerve conduction tests and electromyography (a test which measures the response of muscles to electrical stimulation)

Understanding the Standard Treatments...and the Treatment Options
The primary goals of treatment for peripheral neuropathy include accomplishing the following objectives:

Determining and treating the underlying cause of the condition, if possible.
Controlling and alleviating pain and other bothersome symptoms associated with the condition.
Preserving function of the affected limbs, such as the hands and/or feet.
Preventing a significant decrease in the patient's quality of life.

The management of peripheral neuropathy in patients where the underlying cause can be identified, such as diabetes, autoimmune disorders, infectious diseases, nerve compression, and cancer chemotherapy.
The major types of medications that are often prescribed to relieve pain associated with peripheral neuropathy, which include:
- Antidepressants
- Anticonvulsants
- Selective serotonin reuptake inhibitors
- Narcotic analgesics
- Topical agents such as capsaicin and lidocaine patches
The treatment options that are available for controlling pain that does not adequately respond to drug therapy, including nerve blocks with local anesthetics and spinal cord stimulation.
The role of physical and occupational therapy in functional rehabilitation of patients with peripheral neuropathy.
The role of complementary and alternative therapies in the management of peripheral neuropathy.
The impact of peripheral neuropathy on the patient's psychological well-being and quality of life, including aspects such as:
- Anxiety and depression
- Social relationships
- Activities of daily living
- Employment issues
- Sleep disturbances
- Recreational activities
- Feelings of self-worth
Practical tips and suggestions for how to minimize the negative impact of peripheral neuropathy on your quality of life and learn how to better cope with the condition.
Important questions to ask your doctor about peripheral neuropathy.

A Guide to Recent Medical Literature on Peripheral Neuropathy - This section of the Guidebook contains an extensive bibliography of over 100 references to recently published articles about Peripheral Neuropathy in authoritative, peer-reviewed medical journals with links to the absracts (summaries) of the articles. These articles represent the latest advances in the field and focus on cutting-edge research, new developments, and the lessons learned from recently published clinical trials involving patients with Peripheral Neuropathy. This is the same level of that is used by doctors who treat people with Peripheral Neuropathy to keep abreast of the latest developments and breakthroughs in this specialized field of medicine.
Centers of Research for Peripheral Neuropathy - We've compiled a unique directory of doctors, hospitals, medical centers, and research institutions with special interest and, in many cases, clinical expertise in managing people with Peripheral Neuropathy. The "Centers of Research" directory is a valuable resource for quickly identifying and locating leading medical authorities and medical institutions both within the United States and other countries who are considered to be at the forefront in clinical research and treatment of Peripheral Neuropathy. You'd have to spend days - or even weeks - attempting to compile your own list of doctors and medical centers but, with the "Centers of Research" directory, the information is already right at your fingertips. All you have to do is act on the information by selecting and contacting the experts or medical institutions listed in the directory by state and country.
Organizations and Support Groups for Peripheral Neuropathy - The Guidebook also includes a directory of organizations and support groups whose goal is to help people with Peripheral Neuropathy by providing access to information, resources, and services. Many of these organizations can answer your specific questions, enable you to "network" with other patients, and provide guidance in areas such as financial, social, or medical-legal issues. This valuable directory of organizations and support groups includes complete contact information, including phone numbers and E-mail addresses.

Free Updates for One Year - With your initial purchase of the Guidebook, you also receive access to free updates for one-full year. The Guidebook is updated with new information every 4 to 6 months, so that you will be able to access the updated information several times during the course of a year for up to one full year after the date of your initial purchase.
Free Digest E-Mail Alerts - When you purchase the Guidebook, you will also automatically receive a free subscription to our monthly newsletter - the Medifocus Digest Alert for Peripheral Neuropathy. This is an expertly selected listing of the latest articles published in the medical literature about Peripheral Neuropathy with convenient links to the abstracts of the articles that focus on cutting-edge research, clinical trials, and the latest treatment advances. The Medifocus Digest Alert for Peripheral Neuropathy is automatically delivered straight to your "inbox" monthly and is a valuable resource for keeping up with the latest developments in Peripheral Neuropathy almost as soon as the new information is published in the medical literature.
10% Discount - For a limited time, you can purchase the Medifocus Guidebook on Peripheral Neuropathy at a special 10% discount off the regular list price. Your 10% discount will automatically be applied when you go to "Checkout".
Risk-Free Satisfaction Guarantee - Your purchase comes with our RISK-FREE satisfaction guarantee. If, for whatever reason, you are not totally satisfied with the content of your Guidebook, simply contact us within 30-days of your purchase for a prompt, full refund. We are so confident that you will be satisfied with your Guidebook that we offer this RISK-FREE satisfaction guarantee unconditionally - no questions and no hassles.

Retinal - Vitamin A

2011-06-12T00:16:00.003-07:00

Overview & Description

Vitamin A is a fat-soluble vitamin which means it can be dissolved in fat. Vitamin A is carried through the body by fat. The body can store this type of vitamin in fat tissue. Getting too much can be harmful.

Information

Vitamin A is usually measured in retinol equivalents, also called RE. The Recommended Dietary Allowance, called RDA, for vitamin A for adult men, from age 11 on, is 1,000 RE per day. Women, from age 11 on, should get 800 RE per day. There is no increase of vitamin A requirements during pregnancy but lactating women need about 500 RE or more per day.
Vitamin A can be stored in the fat tissues of the body. This can pose a problem for people taking extra doses of vitamin A. High doses can be toxic and cause symptoms such as the following:

headaches

dry and scaly skin

liver damage

bone and joint pain

vomiting or lack of appetite

abnormal bone growth

nerve damage

birth defects

In most cases, only levels 10 times the RDA (far more than a person could get through diet alone) have been linked with these symptoms. Vitamin A cannot reach toxic levels unless a person is taking extra doses. Carotenoids are not converted to vitamin A fast enough to increase the amount of vitamin A stored in the body. Beta-carotene is NOT toxic to the body.
Getting too little vitamin A can cause side effects too. Symptoms of significant deficiency include:

lowered resistance to infections

problems with getting pregnant

poor growth

improper tooth formation

rough, dry, and pimply skin

digestive problems

night blindness

eye disease, including xerophthalmia (zear-off-thal-me-ah), a condition in which the clear covering of the eye known as the cornea becomes dry and dull

Vitamin A is an important fat-soluble vitamin. Eat a variety of fruits, vegetables, lean meats, and fortified dairy products to ensure optimal intake of vitamin A. Read food labels to help choose foods with vitamin A content.

Functions and Sources

What food source is the nutrient found in?

Vitamin A can come from animal sources such as:

eggs

fortified milk

liver

oils of some fish

This form of Vitamin A is called retinal or retinol.
Vitamin A is also found in plants. This form is called carotenoids. Substances such as beta-carotene are converted from carotenoids into vitamin A in the body. Beta-carotene is one of the most common carotenoids. Carotenoids are pigments found in deep orange, red, and yellow fruits and vegetables. They are also found in many dark-green leafy vegetables, such as:

carrots

pumpkin and other squashes

sweet potatoes

cantaloupe

broccoli

spinach

How does the nutrient affect the body?

Vitamin A helps develop and maintain healthy growth in the cells and almost all the parts of the body. It is especially key for proper night vision, but is also needed for the health of a person's:

teeth

skeletal and soft tissue

skin

mucous membranes

Vitamin A plays a key role in the immune system by helping protect from infections. Beta-carotene is an antioxidant. It has been studied for its role in cancer and heart disease protection. Antioxidants help fight free radicals. Free radicals are oxygen by-products produced when body cells burn oxygen. A build up of free radicals can damage body cells and tissues.

Attribution

Author:Clare Armstrong, MS, RD
Date Written:
Editor:Crist, Gayle P., MS, BA
Edit Date:09/27/02
Reviewer:Kathleen A. MacNaughton, RN, BSN
Date Reviewed:09/26/02

Sources

Mahan, K, MS, RD, CDE & Escott-Stump, S., MA, RD, LDN. (2000). Krause's Food, Nutrition, & Diet Therapy (10th ed.). Pennsylvania: W.B. Saunders Company.
Somer, E., MA, RD. & Health Media of America. (1995). The Essential Guide To Vitamins and Minerals (2nd ed.). New York: HarperCollins Publishers, Inc.
Duyff, R., MS, RD, CFCS. (1996). The American Dietetic Association's Complete Food & Nutrition Guide. Minnesota: Chronimed Publishing.

Relapsing Urinary Tract Infection - Recurring Urinary Tract Infection

2011-06-12T00:16:00.001-07:00

Overview, Causes, & Risk Factors

Recurring urinary tract infection (UTI) involves repeated infections of the kidneys or bladder even after proper treatment.

What is going on in the body?

UTIs are usually caused by bacteria. In most cases, the bacteria enter the body through the skin around the genitals and anal area. The bacteria travel up toward the bladder or kidneys. If the bacteria are not killed by the person's immune system, an infection can occur.

What are the causes and risks of the infection?

Recurrent UTIs can occur for many reasons, including:

problems with the immune system

the use of a urinary catheter to empty the bladder

abnormalities in kidneys, ureters, bladder or urethra can cause repeated infections. The ureters are tubes that carry urine from the kidneys to the bladder. The urethra is a tube that carries urine from the bladder to the outside of the body.

damage to part of the urinary system

sexual intercourse, which seems to trigger UTI in some women

poor hygiene, such as wiping from back to front after a bowel movement or not changing the underwear often.

Symptoms & Signs

What are the signs and symptoms of the infection?

A UTI may cause any of the following symptoms:

fever

the need to urinate frequently

painful urination

pain in the abdomen or on the sides of the back below the ribs

nausea and vomiting

incontinence, or involuntary loss of urine

a sensation of fullness in the lower abdomen

blood in the urine

Diagnosis & Tests

How is the infection diagnosed?

A history of the symptoms is taken by a healthcare provider. A urine sample may be sent to a lab for a urinalysis and a urine culture. Infected urine often contains bacteria and white blood cells, the infection-fighting cells of the body. Normal urine contains little or no bacteria or white blood cells.

Prevention & Expectations

What can be done to prevent the infection?

Prevention of recurring urinary tract infections can involve several steps:

A woman who develops UTIs after sexual intercourse may take antibiotics, such as sulfamethoxazole/trimethoprim, before signs of infection occur.

A person who has a urinary catheter in the bladder needs to have the device changed or cleaned often.

Good hygiene is important for everyone, but especially for those who are bedridden and incontinent.

A person should drink 8 glasses of water every day.

A person should urinate when the urge is felt, rather than holding urine in the bladder for long periods of time.

What are the long-term effects of the infection?

Recurring UTIs can damage the urinary system. A UTI can spread to the blood, causing sepsis. That can cause severe illness and even death.

What are the risks to others?

UTIs are usually not contagious. However, infections of the urethra are generally spread through sexual contact.

Treatment & Monitoring

What are the treatments for the infection?

A person who has an abnormality in the urinary system may be able to have surgery to correct the problem. Otherwise, antibiotics, such as sulfamethoxazole/trimethoprim or nitrofurantoin, are given to treat the UTI. A person may need to take these medications for a week or more in difficult cases of recurrent infection.
A person who has an artificial device, such as a urinary catheter, in the bladder should have the device changed or cleaned regularly.

What are the side effects of the treatments?

Antibiotics may cause allergic reactions and stomach upsets. Other side effects vary depending on the medication used.

What happens after treatment for the infection?

The person can usually go back to normal activities once the symptoms have gone away.

How is the infection monitored?

Often, a person with recurring UTIs is asked to give a urine sample after treatment is completed. A urinalysis and urine culture can be done to check that the bacteria are gone from the urinary tract.

Attribution

Author:Adam Brochert, MD
Date Written:
Editor:Coltrera, Francesca, BA
Edit Date:04/14/00
Reviewer:Gail Hendrickson, RN, BS
Date Reviewed:07/27/01

Sources

Principles and Practice of Infectious Diseases, 1995, Mandell et al

Recommended Dietary Allowances (RDA)

2011-06-12T00:15:00.003-07:00

Recommended Dietary Allowances (RDA)

The Recommended Daily Allowances, known as RDAs, are recommendations for nutrients. They were developed by the Food and Nutrition Board of the National Academy of Sciences/National Research Council. They are updated as new research findings surface. The RDAs state the amount of a nutrient that is needed for most people to stay healthy. They are different for children, adults, males, and females.
The Dietary Reference Intakes, known as DRIs, are an umbrella group that includes the following other nutrient measures:

RDAs

Adequate Intakes, known as AI

Estimated Average Intakes, known as EAR

Tolerable Upper Intakes, known as UL

DRIs are slowly becoming the more accepted form for nutrient recommendations. Experts expect that DRIs will take the place of the RDAs in time.

Information

United States Recommended Dietary Allowances (RDA)
Recommended Dietary Allowances: National Academy of Sciences;10th ed., 1989
Dietary Reference Intakes: National Academy of Sciences, 1997

Compound	units	Adult	Adult	Children	Infants	Pregnant	Lactating+
		Males (25+years)	Females (25+years)	4-8 years	6-12 mos.
Biotin	mcg	30*	30*	12*	6*	30*	35*
Calcium (Ca)	mg	1200*	1200*	800*	270*	1000*	1000*
Chloride (Cl)	mg	750	750	600	300	750	750
Chromium (Cr)	mcg	50-200	50-200	50-200	20-60	50-200	50-200
Copper (Cu)	mg	1.5-3	1.5-3	1-2	0.6-0.7	1.5-3	1.5-3
Fluoride (F)	mg	4*	3*	1*	0.5*	3*	3*
Folate	mcg	400*	400*	200*	80*	600*	500*
Iodine(I)	mcg	150	150	120	50	175	200
Iron (Fe)	mg	10	(25-50y) 15 (51+y) 10	10	10	30	15
Magnesium (Mg)	mg	420**	320**	130**	75*	350-400**	310-360**
Manganese (Mn)	mg	2-5	2-5	2-3	0.6-1.0	2-5	2-5
Molybdenum (Mo)	mcg	75-250	75-250	50-150	20-40	75-250	75-250
Niacin	mg	16**	14**	8**	4*	18**	17**
Pantothenic	mg	5*	5*	3*	1.8*	6*	7*
Phosphorus (P)	mg	700**	700**	500**	275*	700**	700**
Potassium(K)	mg	2000	2000	1600	700	2000	2000
Protein	g	63	50	28	14	60	65
Selenium (Se)	mcg	70	55	30	15	65	75
Sodium (Na)	mg	500	500	400	200	500	500
Vitamin A	mcgRE*	1000	800	700	375	800	1300
Vitamin B1(Thiamine)	mg	1.2**	1.1**	0.6**	0.3*	1.4**	1.5**
Vitamin B2 (Riboflavin)	mg	1.3**	1.1**	0.6**	0.4*	1.4**	1.6**
Vitamin B6 (Pyridoxine)	mg	1.7**	1.5**	0.6**	0.3*	1.9**	2.0**
Vitamin B12 (Cyanocobalamin)	mcg	2.4**	2.4**	1.2**	0.5*	2.6**	2.8**
Vitamin C	mg	60	60	45	35	95	90
Vitamin D	mcg	(51-70y) 10* (71+y) 15*	(51-70y) 10* (71+y) 15*	(1-8y) 5*	5*	5*	5*
Vitamin E	mg alpha TE*	10	8	7	4	12	11
Vitamin K	mcg	80	65	30	10	65	65
Zinc (Zn)	mg	15	12	10	5	15	19

g =grams
mg = milligrams (0.001 g)
mcg = micrograms (0.000001g)
IU = International Units
RE = Retinol Equivalent
Alpha TE = alpha Tocopherol equivalent
+ Generally the higher number was reported.
* AI (Adequate Intake) from the new Dietary Reference Intakes, 1997: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Values have changed from previous RDA.
** RDA (Recommended Dietary Allowance) from the new Dietary Reference Intakes, 1997: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Values have changed from previous RDA.

Radial Nerve Damage - Radial Nerve Injury

2011-06-12T00:15:00.001-07:00

Overview, Causes, & Risk Factors

A radial nerve injury involves damage to the radial nerve, which allows sensation and movement in part of the arm. The radial nerve attaches to the skin and muscles of certain areas of the arm, forearm, and hand. It is responsible for muscle movement and sensation in these areas. Someone with an injury to the radial nerve lose function in these areas.
In most cases, the radial nerve is damaged by trauma, repeated use of the nerve, or by the nerve being compressed by other structures. The injury may be permanent.

What are the causes and risks of the injury?

Radial nerve injury can be caused by a number of activities, including:

the improper use of crutches, usually when a person rests his or her weight on the armpits rather than the hands

hanging the arms over the back of a chair for too long or lying on an arm for too long. This is sometimes called "Saturday night palsy," because it often happens in those who are very drunk or intoxicated.

a bone fracture involving the upper arm bone, or humerus

Rarely, no cause can be found for the nerve damage. In these cases, the injury may come from certain repeated motions of the arm, known as a repetitive stress injury.
A radial nerve injury may be permanent, causing lifelong weakness and numbness, and sometimes chronic pain. In some people, the muscles can shrink and cause the arm to become deformed over time. In other people, some or all of the arm's function may be regained over time.

Symptoms & Signs

What are the signs and symptoms of the injury?

Symptoms of a radial nerve injury depend on where the nerve injury occurs, but may include:

numbness or tingling of the skin on the back of the arm, forearm, and hand

pain in the same areas as the numbness or tingling

muscle weakness, which usually affects the ability to straighten the elbow, wrist, and fingers

muscle shrinkage or wasting, which takes a long time to develop

deformities in the hand or forearm, usually due to muscle wasting

Symptoms may also result from the injury that caused the nerve damage.

Diagnosis & Tests

How is the injury recognized?

A radial nerve injury can often be diagnosed with a history and physical exam. Tests may be ordered to help figure out the cause of the nerve injury. An x-ray of the arm is commonly done to look for a break or other bone injury. A test called a nerve conduction velocity (NCV) study may be done to determine the location of the nerve injury. This test involves attaching wires to the skin. Small shocks are used to stimulate the nerve and measure its function.
Blood tests or a nerve biopsy are sometimes needed in unusual cases. A biopsy is a procedure to remove a small piece of tissue from the body. A special tool or needle can be inserted through the skin and into the nerve. A small piece of the nerve can be removed with the tool. The piece can then be sent to the lab for further examination and testing.

Prevention & Expectations

What can be done to prevent the injury?

Most cases of radial nerve injury cannot be prevented. Avoiding injury, overuse of the arm, and improper use of crutches can prevent some cases.

Treatment & Monitoring

What are the treatments for the injury?

When the radial nerve injury is caused by a broken bone, fixing the bone may reverse the nerve injury or make it better. This may involve surgery or the use of a cast. Other treatments may include:

pain medications, such as aspirin

other medications to help with nerve pain, such as amitriptyline or gabapentin

physical therapy to help improve arm use and strength

occupational therapy to help the person improve his or her ability to perform daily activities

What are the side effects of the treatments?

Surgery may cause bleeding, infection, or allergic reaction to anesthesia. Aspirin and other pain medications may cause stomach upset, allergic reactions, or kidney damage. Other side effects depend on the specific medication used.

What happens after treatment for the injury?

Treatment for a radial nerve injury may or may not be able to reverse the lost function in the person's arm. Someone who does not recover fully often benefits from long-term physical therapy and occupational therapy. Deformity of the hand and muscle shrinkage can occur in severe cases. Some people may recover completely and need no further treatment.
The healthcare provider can help people monitor the injury by measuring the strength and sensation in the affected areas. Some of the medications used to treat pain may also need monitoring, which can include blood tests. Any new or worsening symptoms should be reported to the healthcare provider.

Attribution

Author:James Broomfield, MD
Date Written:
Editor:Duff, Ellen, BA
Edit Date:10/09/00
Reviewer:Adam Brochert, MD
Date Reviewed:07/01/01

Sources

Harrison's Principles of Internal Medicine, Fauci et al, 1998

RA - Rheumatoid Arthritis

2011-06-12T00:14:00.001-07:00

Overview, Causes, & Risk Factors

Rheumatoid arthritis, also called RA, is an inflammation in the lining of the joints and other internal body organs. RA belongs to a group of diseases called autoimmune disorders, in which the body makes antibodies against its own tissues. It is a fairly common form of arthritis.

What is going on in the body?

In RA, for reasons unknown, the body's immune system malfunctions and begins making antibodies against its own tissues. Antibodies are proteins that help the body to fight infection. These antibodies are made by the immune system in response to a trigger called an antigen. This trigger is often a substance that the body sees as "foreign." These foreign substances can include things like bacteria and viruses. This immune reaction causes an inflammation of the synovial membrane lining the joints.
This chronic inflammation produces enzymes that can invade and damage cartilage and bone within the joint. Sometimes this form of arthritis is mild, but 70% of people who have it develop chronic problems, and 15% have severe crippling disease. Young children can have a form called juvenile RA.

What are the causes and risks of the disease?

The causes of RA are not yet fully understood. Experts suspect that some type of virus can trigger RA in people who have certain genes that give one a tendency to develop the disease.
RA affects 2.1 million people in the U.S. and can develop at any age. Most often, it starts in middle age, but it is also common in people in their 20s and 30s. More than 70% of the people who have RA are women.
There is currently research into a number of factors that may trigger RA, including:

certain abnormal genes found in some, but not all, people who have RA

certain viruses or bacteria that trigger the autoimmune response of RA

hormone imbalances

Symptoms & Signs

What are the signs and symptoms of the disease?

Joint pain, swelling, and stiffness that is especially severe and prolonged in the morning are the most common symptoms of RA. The same joint on both sides of the body is usually involved, and RA most often starts in the hands or feet. However, the problems may move from one joint to another. Usually many joints throughout the body are affected at the same time.
Because RA is a disease that can affect the whole body, the person may have other symptoms:

fatigue

a vague feeling of illness called malaise

occasional fever

loss of appetite

loss of energy

lumps of tissue under the skin called rheumatoid nodules, often over bony areas exposed to pressure (especially near the elbow)

Diagnosis & Tests

How is the disease diagnosed?

Observing the person and his or her pattern of symptoms, along with a medical history and physical exam, helps the doctor to diagnose RA. A blood test for the rheumatoid factor is positive in about 80% of cases but does not mean the person has RA.
Other blood tests, such as a complete blood count, called CBC; C4 complement components; C-reactive proteins, called CRP; and antinuclear antibody, called ANA; tests may be done. People with RA are often anemic and have a low number of red blood cells in their blood count. Joint aspiration, which means removing joint fluid with a needle under local anesthesia, might be done. Synovial fluid that is cloudy, milky, or dark yellow and that contains many inflammatory cells will help detect RA.
Joint X-rays may also be ordered to help diagnose RA. It is important to rule out other diseases and conditions, such as other types of arthritis, as well as condition such as systemic lupus erythematosus and Borrelia burgdorferi.\ It is passed to humans through tick bites. ',CAPTION,'Lyme Disease');" onmouseout="return nd();">Lyme disease.

Prevention & Expectations

What can be done to prevent the disease?

RA can't be prevented.

What are the long-term effects of the disease?

RA may be progressive and can affect many joints. This can make walking very difficult and can interfere greatly with the function of the hands. Disability can be severe and may cause depression.
Rheumatoid arthritis can cause deformities such as misshapen fingers, bunions, hammertoe, and knock-knees. The affected joints are swollen and warm.
Other body parts can also be affected by rheumatoid arthritis. The rheumatoid process can involve the eye, known as episcleritis, and the lungs, known as interstitial disease. There may be an inflammation of blood vessels or the lining around the heart, known as vasculitis or pericarditis. Osteoporosis, which is the loss of bone density, is also more common in people who have RA than in the larger population.

What are the risks to others?

RA poses no risk to others.

Treatment & Monitoring

What are the treatments for the disease?

People who have RA should learn all they can about self-care and managing their disease. There are many treatment approaches.
Overview
Early treatment is the key. Effective self-management of RA will focus on the following goals:

relieve pain

decrease inflammation in the joints

slow down or stop damage to the joints

improve joint function and ability to do daily activities

increase feelings of general well-being

Specific self-care measures may include:

managing one's stress

applying splints to rest acutely inflamed joints

using assistive devices, such as zipper pulls, to decrease strain on joints

Medicine
Symptom control and disease management may be enhanced when medicines are started early in treatment. A wide variety of highly effective medicines are used to treat RA. Most fall into one of two groups, including medicines that relieve symptoms and medicines that actually modify the disease process. These two types of medicines are sometimes used in combination. Examples of medicines that relieve symptoms include:

anti-inflammatory medicines, called NSAIDs, such as aspirin, naproxen, and ibuprofen

COX-2 specific inhibitor NSAIDs, such as celecoxib and rofecoxib

corticosteroids, such as prednisone, which can be taken orally or by injection into the joint

analgesics, such as acetaminophen or propoxyphene

Examples of medicines that modify disease include:

immunosuppressant medicines, which alter the body's immune response, such as methotrexate, azathioprine, and cyclophosphamide

anti-inflammatory medicines, such as infliximab and etanercept, which block the effects of a key protein involved in the rheumatoid process

antibiotics, such as doxycycline and minocycline

medicines that slow down joint destruction, such as d-penicillamine, sulfasalazine, hydroxychloroquine, and gold

Diet and Nutrition
All people should be sure to eat a healthy diet, following the food guide pyramid. It's important to get the right amount of calories, protein, and calcium.
The findings of some studies have shown that symptoms of RA improve with high doses of omega-3 fatty acids. These substances occur naturally in certain fish and in some plant seeds. However, it is hard to get enough of these acids to affect the disease, and some people cannot tolerate the high doses.
There has been a great deal of interest in the last few years in the use of glucosamine and chondroitin, dietary supplements that may decrease the joint pain linked with another form of arthritis called osteoarthritis. People who have RA should discuss the value of such supplements with their doctors before taking them.
Exercise
Exercise is a key strategy in the treatment of arthritis, but the person with RA needs to be careful to balance exercise and rest to conserve energy. The exercise program should consist of a combination of aerobic exercise, strengthening (joint protection) exercises, and flexibility (or stretching) exercises.

For aerobic exercise, 30 minutes of moderate exercise a day can help prevent complications of arthritis, as well as heart disease, stroke, and diabetes. Exercise should be kept to a level where the person can talk without shortness of breath and is comfortable with the pace of the activity. The 30 minutes a day can be done in one session or broken up into several shorter segments. Walking and water aerobics are exercises that keep joint stress to a minimum.

Strengthening exercises can be done with light weights or a resistance band. The goal is to build strength and tone in the muscles around the joints affected by RA, rather than to build big muscles. Improving muscle strength and tone can help protect the joint and prevent further joint damage. Most people with RA should talk with a doctor or physical therapist to set up a program that is right for him or her.

Stretching exercises will help maintain flexibility and should be done each day. They can be done while lying in bed or in various positions or at different times during the day.

Surgery
Surgery may be performed when pain cannot be controlled or when significant function is lost. Several types of surgery may be done, such as:

arthroscopy, a procedure that uses a small scope and instruments to get inside the joint without opening it

arthrotomy, which means opening the joint through a larger incision

synovectomy, which is the removal of the lining of the joint

osteotomy, which realigns the bone next to the joint

arthroplasty, which is the partial or total replacement of the joint. People with severe arthritis are often candidates for a knee joint replacement or a hip joint replacement.

Prosorba Therapy
The Food and Drug Administration has approved a blood-filtering treatment called Prosorba for moderate to severe cases of RA that have not responded well to disease-modifying medicines. In this procedure, blood is drawn from the arm and then separated into two different parts called the plasma and the red blood cells. Next, the plasma is filtered through a special cylinder the size of a soup can that is filled with a sandlike substance. This is called a Prosorba column, and the filtering sand in it is coated with protein A, which removes certain antibodies from the plasma. These antibodies contribute to pain and inflammation in the joints. The plasma is then combined again with the red blood cells and put back into the person's body.
Therapy is given once a week for 12 weeks as an outpatient procedure. Each session lasts 2 to 2.5 hours. This therapy can bring remission from RA symptoms, but it will take up to 12 to 16 weeks before the person begins to feel the benefits. Once remission is reached, it may last as long as a year and a half.

What are the side effects of the treatments?

Medicines used to treat RA may cause stomach upset or bleeding , allergic reaction, less resistance to infection, and other side effects. Surgery may cause bleeding, infection, or allergic reaction to anesthesia. Nearby bones, ligaments, tendons, nerves, or blood vessels can also be injured by accident.

What happens after treatment for the disease?

Treatment of RA is lifelong. There is no cure for the disease, but careful management can help to reduce some of its effects.

How is the disease monitored?

A doctor will watch the person's level of comfort and function of the joint. Any new or worsening symptoms should be reported to the doctor.

Attribution

Author:John A.K. Davies, MD
Date Written:
Editor:Crist, Gayle P., MS, BA
Edit Date:09/28/02
Reviewer:Kathleen A. MacNaughton, RN, BSN
Date Reviewed:09/25/02

GUANIDINEHYDROCHLORIDETablets

2011-06-12T00:13:00.004-07:00

DESCRIPTION

Chemically, guanidine (aminomethanamidine) hydrochloride is a crystalline powder freely soluble in water and alcohol. The aqueous solution is neutral.
The structural formula is:
Each tablet contains 125 mg of guanidine hydrochloride with no color additive in the base. It also contains the following inactive ingredients: colloidal silicon dioxide, magnesium stearate, mannitol, and microcrystalline cellulose.

CLINICAL PHARMACOLOGY

Guanidine apparently acts by enhancing the release of acetylcholine following a nerve impulse. It also appears to slow the rates of depolarization and repolarization of muscle cell membranes.

INDICATIONS AND USAGE

Guanidine is indicated for the reduction of the symptoms of muscle weakness and easy fatigability associated with the myasthenic syndrome of Eaton-Lambert. It is not indicated for treating myasthenia gravis. The Eaton-Lambert syndrome is ordinarily differentiated from myasthenia gravis by the usual association of the syndrome with small cell carcinoma of the lung, but myography may be necessary to make the diagnosis.

CONTRAINDICATIONS

Guanidine is contraindicated in individuals with a history of intolerance or allergy to this drug.

WARNINGS

Fatal bone-marrow suppression, apparently dose related, can occur with guanidine.
Safe use of guanidine hydrochloride in pregnancy has not been established. Therefore, the benefits of therapy must be weighed against the potential hazards. Because guanidine is excreted in milk, patients on this drug should discontinue breast-feeding.
Since there is inadequate experience in children who have received this drug, safety and efficacy in children have not been established.

PRECAUTIONS

Baseline blood studies should be followed by frequent red and white blood cell and differential counts. The drug should be discontinued upon appearance of bone-marrow suppression. Concurrent therapy with other drugs that may cause bone-marrow suppression should be avoided.
Renal function may be affected in some patients receiving guanidine. Patients should therefore have regular urine examinations and serum creatinine determinations while taking this drug.
Physicians should be given adequate precautions pertaining to the gastrointestinal side effects and the possibility of induced behavior disorders.
Treatment should not be continued longer than necessary.

ADVERSE REACTIONS

Anemia, leukopenia, and thrombocytopenia resulting from bone-marrow suppression attributable to guanidine have been reported. Other adverse reactions that have been observed are:
General: sore throat, rash, fever.
Neurologic: paresthesia of lips, face, hands, feet; cold sensations in hands and feet; nervousness, lightheadedness, jitteriness, increased irritability; tremor, trembling sensation; ataxia; emotional lability; psychotic state; confusion; mood changes, and hallucinations.
Gastrointestinal: dry mouth; gastric irritation; anorexia; nausea; diarrhea; abdominal cramping. Gastrointestinal side effects may preclude the use of guanidine as a desired form of therapy.
Dermatologic: rash, flushing or pink complexion; folliculitis; petechiae, purpura, ecchymoses; sweating; skin eruptions; dryness and scaling of the skin.
Renal: elevation of blood creatinine, uremia; chronic interstitial nephritis, acute interstitial nephritis, and renal tubular necrosis.
Hepatic: abnormal liver function tests.
Cardiac: palpitation, tachycardia, atrial fibrillation, hypotension.

DOSAGE AND ADMINISTRATION

Initial dosage is usually between 10 and 15 mg/kg (5 to 7 mg/pound) of body weight per day in 3 or 4 divided doses. This dosage may be gradually increased to a total daily dosage of 35 mg/kg (16 mg/pound) of body weight per day or up to the development of side effects. As individual tolerance is highly variable, the dosage must be carefully titrated. Once a tolerable dose has been established, it should be continued. Occasionally removal of the primary neoplastic lesion may result in improvement of symptoms, permitting the discontinuance of guanidine.

OVERDOSAGE

Mild gastrointestinal disorders, such as anorexia, increased peristalsis, or diarrhea are early warnings that tolerance is being exceeded. These symptoms may be relieved by atropine, but nevertheless note should be taken of these symptoms and dosage reductions considered. Slight numbness or tingling of the lips and fingertips shortly after taking a dose of guanidine has been reported. This per se is not an indication to discontinue treatment and/or reduce dosage.
Severe guanidine intoxication is characterized by nervous hyperirritability, fibrillary tremors and convulsive contractions of muscle, salivation, vomiting, diarrhea, hypoglycemia, and circulatory disturbances. Administration of intravenous calcium gluconate may control the neuromuscular and convulsive symptoms and provide some relief of other toxic manifestations.
Atropine is more effective than calcium in relieving the G.I. symptoms, circulatory disturbances, and changes in blood sugar.

HOW SUPPLIED

Guanidine hydrochloride tablets: 125 mg, white, round tablet; impressed with the product identification number "KEY 74" on one side. Guanidine hydrochloride tablets are available in bottles of 100 (NDC 0085-0492-01).
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

Manufactured by
Schering Canada, Inc.
Pointe Claire, Quebec, Canada for
Key Pharmaceuticals, Inc.
Kenilworth, NJ 07033 USA
27051812
81-483544
Copyright © 1987, 1992,
Key Pharmaceuticals, Inc.,
Kenilworth, NJ 07033
USA. All rights reserved.

GENTAMICIN SULFATE CREAM USP, 0.1%

2011-06-12T00:13:00.002-07:00

For Dermatologic Use Only
Not For Ophthalmic Use
Rx Only

DESCRIPTION

Gentamicin Sulfate Cream is a wide spectrum antibiotic preparation for topical administration. Each gram contains Gentamicin Sulfate USP equivalent to 1 mg gentamicin base in a cream base containing stearic acid, propylene glycol monostearate, isopropyl myristate, polysorbate 40, propylene glycol, sorbitol solution and purified water with methylparaben and butylparaben as preservatives.

CLINICAL PHARMACOLOGY

Gentamicin sulfate is a wide spectrum antibiotic that provides highly effective topical treatment in primary and secondary bacterial infections of the skin. Gentamicin Sulfate Cream may clear infections that have not responded to treatment with other topical antibiotic agents. In primary skin infections such as impetigo contagiosa, treatment 3 or 4 times daily with Gentamicin Sulfate Cream usually clears the lesions promptly. In secondary skin infections, Gentamicin Sulfate Cream aids in the treatment of the underlying dermatoses by controlling the infection. Bacteria susceptible to the action of gentamicin sulfate include sensitive strains of Streptococci (group A beta-hemolytic, alpha-hemolytic), Staphylococcus aureus (coagulase positive, coagulase negative, and some penicillinase-producing strains), and the gram-negative bacteria, Pseudomonas aeruginosa, Aerobacter aerogenes, Escherichia coli, Proteus vulgaris, and Kiebsiella pneumoniae.

INDICATIONS AND USAGE

Primary skin infections: Impetigo contagiosa, superficial folliculitis, ecthyma, furunculosis, sycosis barbae, and pyoderma gangrenosum. Secondary skin infections: Infectious eczematoid dermatitis, pustular acne, pustular psoriasis, infected seborrheic dermatitis, infected contact dermatitis (including poison ivy), infected excoriations, and bacterial super-infections of fungal or viral infections. Please Note: Gentamicin sulfate is a bactericidal agent that is not effective against viruses or fungi in skin infections. Gentamicin sulfate is useful in the treatment of infected skin cysts and certain other skin abscesses when preceded by incision and drainage to permit adequate contact between the antibiotic and the infecting bacteria. Good results have been obtained in the treatment of infected stasis and other skin ulcers , infected superficial burns, paronychia, infected insect bites and stings, infected lacerations and abrasions, and wounds from minor surgery. Patients sensitive to neomycin can be treated with gentamicin sulfate, although regular observation of patients sensitive to topical antibiotics is advisable when such patients are treated with any topical antibiotic. Gentamicin sulfate cream is recommended for wet, oozing primary infections, and greasy, secondary infections, such as pustular acne or infected seborrheic dermatitis. If a water-washable preparation is desired, the cream is preferable. Gentamicin sulfate cream has been used successfully in infants over one year of age, as well as in adults and children.

CONTRAINDICATIONS

This drug product is contraindicated in individuals with a history of sensitivity to any of its components.

PRECAUTIONS

The use of topical antibiotics occasionally allows overgrowth of nonsusceptible organisms, including fungi. If this condition occurs, or if irritation, sensitization or superinfection develops, treatment with gentamicin sulfate should be discontinued and appropriate therapy instituted.

ADVERSE REACTIONS

In patients with dermatoses treated with gentamicin sulfate, irritation (erythema and pruritis) that did not usually require discontinuance of treatment has been reported in a small percentage of cases. There was no evidence of irritation or sensitization, however, in any of these patients patch-tested subsequently with gentamicin sulfate on normal skin. Possible photosensitization has been reported in several patients but could not be elicited in these patients by reapplication of gentamicin sulfate followed by exposure to ultraviolet radiation.

DOSAGE AND ADMINISTRATION

A small amount of gentamicin sulfate cream should be applied gently to the lesions three or four times daily. The area treated may be covered with a gauze dressing if desired. In impetigo contagiosa, the crusts should be removed before application of gentamicin sulfate to permit maximum contact between the antibiotic and the infection. Care should be exercised to avoid further contamination of the infected skin. Infected stasis ulcers have responded well to treatment with gentamicin sulfate under gelatin packing.

HOW SUPPLIED

Gentamicin Sulfate Cream USP, 0.1% is supplied in 15 gram tubes NDC 0168-0071-15.
Store at controlled room temperature 15°-30°C (59°-86°F).
E. FOUGERA & CO.
a division of Altana Inc.
MELVILLE, NEW YORK 11747
I27115C
#294
R3/98

GEMZAR(GEMCITABINE HCl)FORINJECTION

2011-06-12T00:13:00.000-07:00

GEMZAR^®
(GEMCITABINE HCl)
FOR INJECTION

DESCRIPTION

Gemzar^® (gemcitabine HCl) is a nucleoside analogue that exhibits antitumor activity. Gemcitabine HCl is 2′-deoxy-2′,2′-difluorocytidine monohydrochloride (β–isomer).
The structural formula is as follows:
The empirical formula for gemcitabine HCl is C₉H₁₁F₂N₃O₄ • HCl. It has a molecular weight of 299.66.
Gemcitabine HCl is a white to off–white solid. It is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol and polar organic solvents.
The clinical formulation is supplied in a sterile form for intravenous use only. Vials of Gemzar contain either 200 mg or 1 g of gemcitabine HCl (expressed as free base) formulated with mannitol (200 mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile lyophilized powder. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.

CLINICAL PHARMACOLOGY

Human Pharmacokinetics

Gemcitabine disposition was studied in 5 patients who received a single 1000 mg/m²/30 minute infusion of radiolabeled drug. Within one (1) week, 92% to 98% of the dose was recovered, almost entirely in the urine. Gemcitabine (<10%) and the inactive uracil metabolite, 2′–deoxy–2′,2′–difluorouridine (dFdU), accounted for 99% of the excreted dose. The metabolite dFdU is also found in plasma. Gemcitabine plasma protein binding is negligible.
The pharmacokinetics of gemcitabine were examined in 353 patients, about 2/3 men, with various solid tumors. Pharmacokinetic parameters were derived using data from patients treated for varying durations of therapy given weekly with periodic rest weeks and using both short infusions (<70 minutes) and long infusions (70 to 285 minutes). The total Gemzar dose varied from 500 to 3600 mg/m².
Gemcitabine pharmacokinetics are linear and are described by a 2–compartment model. Population pharmacokinetic analyses of combined single and multiple dose studies showed that the volume of distribution of gemcitabine was significantly influenced by duration of infusion and gender. Clearance was affected by age and gender. Differences in either clearance or volume of distribution based on patient characteristics or the duration of infusion result in changes in half–life and plasma concentrations. Table 1 shows plasma clearance and half–life of gemcitabine following short infusions for typical patients by age and gender.

Table 1: Gemcitabine Clearance and Half–Life for the “Typical” Patient
Age	Clearance Men (L/hr/m²)	Clearance Women (L/hr/m²)	Half–LifeHalf–life for patients receiving a short infusion (<70 min). Men (min)	Half–Life Women (min)
29	92.2	69.4	42	49
45	75.7	57.0	48	57
65	55.1	41.5	61	73
79	40.7	30.7	79	94

Gemcitabine half–life for short infusions ranged from 42 to 94 minutes, and the value for long infusions varied from 245 to 638 minutes, depending on age and gender, reflecting a greatly increased volume of distribution with longer infusions. The lower clearance in women and the elderly results in higher concentrations of gemcitabine for any given dose.
The volume of distribution was increased with infusion length. Volume of distribution of gemcitabine was 50 L/m² following infusions lasting<70 minutes, indicating that gemcitabine, after short infusions, is not extensively distributed into tissues. For long infusions, the volume of distribution rose to 370 L/m², reflecting slow equilibration of gemcitabine within the tissue compartment.
The maximum plasma concentrations of dFdU (inactive metabolite) were achieved up to 30 minutes after discontinuation of the infusions and the metabolite is excreted in urine without undergoing further biotransformation. The metabolite did not accumulate with weekly dosing, but its elimination is dependent on renal excretion, and could accumulate with decreased renal function.
The effects of significant renal or hepatic insufficiency on the disposition of gemcitabine have not been assessed.
The active metabolite, gemcitabine triphosphate, can be extracted from peripheral blood mononuclear cells. The half–life of the terminal phase for gemcitabine triphosphate from mononuclear cells ranges from 1.7 to 19.4 hours.

Drug Interactions

When Gemzar (1250 mg/m² on Days 1 and 8) and cisplatin (75 mg/m² on Day 1) were administered in NSCLC patients, the clearance of gemcitabine on Day 1 was 128 L/hr/m² and on Day 8 was 107 L/hr/m². The clearance of cisplatin in the same study was reported to be 3.94 mL/min/m² with a corresponding half–life of 134 hours (see Drug Interactions under PRECAUTIONS). Analysis of data from metastatic breast cancer patients shows that, on average, Gemzar has little or no effect on the pharmacokinetics (clearance and half–life) of paclitaxel and paclitaxel has little or no effect on the pharmacokinetics of Gemzar. Data from NSCLC patients demonstrate that Gemzar and carboplatin given in combination does not alter the pharmacokinetics of Gemzar or carboplatin compared to administration of either single-agent. However, due to wide confidence intervals and small sample size, interpatient variability may be observed.

CLINICAL STUDIES

Ovarian Cancer

Gemzar was studied in a randomized Phase 3 study of 356 patients with advanced ovarian cancer that had relapsed at least 6 months after first–line platinum–based therapy. Patients were randomized to receive either Gemzar 1000 mg/m² on Days 1 and 8 of a 21–day cycle and carboplatin AUC 4 administered after Gemzar on Day 1 of each cycle or single–agent carboplatin AUC 5 administered on Day 1 of each 21–day cycle as the control arm. The primary endpoint of this study was progression free survival (PFS).
Patient characteristics are shown in Table 2. The addition of Gemzar to carboplatin resulted in statistically significant improvement in PFS and overall response rate as shown in Table 3 and Figure 1. Approximately 75% of patients in each arm received post–study chemotherapy. Only 13 of 120 patients with documented post–study chemotherapy regimen in the carboplatin arm received Gemzar after progression. There was not a significant difference in overall survival between arms.

Table 2: Gemzar Plus Carboplatin Versus Carboplatin in Ovarian Cancer – Baseline Demographics and Clinical Characteristics
	Gemzar/Carboplatin	Carboplatin
Number of randomized patients	178	178
Median age, years	59	58
Range	36 to 78	21 to 81
Baseline ECOG performance status 0–1Nine patients (5 on the Gemzar plus carboplatin arm and 4 on the carboplatin arm) did not have baseline Eastern Cooperative Oncology Group (ECOG) performance status recorded.	94%	95%
Disease Status
Evaluable	7.9%	2.8%
Bidimensionally measurable	91.6%	95.5%
Platinum–free intervalThree patients (2 on the Gemzar plus carboplatin arm and 1 on the carboplatin arm) had a platinum–free interval of less than 6 months.
6–12 months	39.9%	39.9%
>12 months	59.0%	59.6%
First–line therapy
Platinum–taxane combination	70.2%	71.3%
Platinum–non–taxane combination	28.7%	27.5%
Platinum monotherapy	1.1%	1.1%

Table 3: Gemzar Plus Carboplatin Versus Carboplatin in Ovarian Cancer – Results of Efficacy Analysis
	Gemzar/Carboplatin (N=178)	Carboplatin (N=178)
PFS
Median (95%, C.I.) months	8.6 (8.0, 9.7)	5.8 (5.2, 7.1)	p=0.0038Log Rank, unadjusted
Hazard Ratio (95%, C.I.)	0.72 (0.57, 0.90)
Overall Survival
Median (95%, C.I.) months	18.0 (16.2, 20.3)	17.3 (15.2, 19.3)	p=0.8977
Hazard Ratio (95%, C.I.)	0.98 (0.78, 1.24)
AdjustedTreatment adjusted for performance status, tumor area, and platinum–free interval. Hazard Ratio (95%, C.I.)	0.86 (0.67, 1.10)
Investigator Reviewed
Overall Response Rate	47.2%	30.9%	p=0.0016Chi Square
CR	14.6%	6.2%
PR+PRNMPartial response non–measurable disease	32.6%	24.7%
Independently Reviewed
Overall Response RateIndependent reviewers could not evaluate disease demonstrated by sonography or physical exam.Independently reviewed cohort – Gemzar/Carboplatin N=121, Carboplatin N=101	46.3%	35.6%	p=0.11
CR	9.1%	4.0%
PR+PRNM	37.2%	31.7%

Figure 1: Kaplan–Meier Curve of Progression Free Survival in Gemzar Plus Carboplatin Versus Carboplatin in Ovarian Cancer (N=356)

Breast Cancer

Data from a multi–national, randomized Phase 3 study (529 patients) support the use of Gemzar in combination with paclitaxel for treatment of breast cancer patients who have received prior adjuvant/neoadjuvant anthracycline chemotherapy unless clinically contraindicated. Gemzar 1250 mg/m² was administered on Days 1 and 8 of a 21–day cycle with paclitaxel 175 mg/m² administered prior to Gemzar on Day 1 of each cycle. Single–agent paclitaxel 175 mg/m² was administered on Day 1 of each 21–day cycle as the control arm.
The addition of Gemzar to paclitaxel resulted in statistically significant improvement in time to documented disease progression and overall response rate compared to monotherapy with paclitaxel as shown in Table 4 and Figure 2. Further, there was a strong trend toward improved survival for the group given Gemzar based on an interim survival analysis.

Table 4: Gemzar Plus Paclitaxel Versus Paclitaxel in Breast Cancer
	Gemzar/Paclitaxel	Paclitaxel
Number of patients	267	262
Median age, years	53	52
Range	26 to 83	26 to 75
Metastatic disease	97.0%	96.9%
Baseline KPSKarnofsky Performance Status. ≥90	70.4%	74.4%
Number of tumor sites
1–2	56.6%	58.8%
≥3	43.4%	41.2%
Visceral disease	73.4%	72.9%
Prior anthracycline	96.6%	95.8%

Time to Documented Disease ProgressionThese represent reconciliation of investigator and Independent Review Committee assessments according to a predefined algorithm.			p<0.0001
Median (95%, C.I.), months	5.2 (4.2, 5.6)	2.9 (2.6, 3.7)
Hazard Ratio (95%, C.I.)	0.650 (0.524, 0.805)		p<0.0001
Overall Response Rate			p<0.0001
(95%, C.I.)	40.8% (34.9, 46.7)	22.1% (17.1, 27.2)

Figure 2: Kaplan–Meier Curve of Time to Documented Disease Progression in Gemzar Plus Paclitaxel Versus Paclitaxel Breast Cancer Study (N=529).

Non–Small Cell Lung Cancer (NSCLC)

Data from 2 randomized clinical studies (657 patients) support the use of Gemzar in combination with cisplatin for the first–line treatment of patients with locally advanced or metastatic NSCLC.
Gemzar plus cisplatin versus cisplatin: This study was conducted in Europe, the US, and Canada in 522 patients with inoperable Stage IIIA, IIIB, or IV NSCLC who had not received prior chemotherapy. Gemzar 1000 mg/m² was administered on Days 1, 8, and 15 of a 28–day cycle with cisplatin 100 mg/m² administered on Day 1 of each cycle. Single–agent cisplatin 100 mg/m² was administered on Day 1 of each 28–day cycle. The primary endpoint was survival. Patient demographics are shown in Table 5. An imbalance with regard to histology was observed with 48% of patients on the cisplatin arm and 37% of patients on the Gemzar plus cisplatin arm having adenocarcinoma.
The Kaplan–Meier survival curve is shown in Figure 3. Median survival time on the Gemzar plus cisplatin arm was 9.0 months compared to 7.6 months on the single–agent cisplatin arm (Log rank p=0.008, two–sided). Median time to disease progression was 5.2 months on the Gemzar plus cisplatin arm compared to 3.7 months on the cisplatin arm (Log rank p=0.009, two–sided). The objective response rate on the Gemzar plus cisplatin arm was 26% compared to 10% with cisplatin (Fisher’s Exact p<0.0001, two–sided). No difference between treatment arms with regard to duration of response was observed.
Gemzar plus cisplatin versus etoposide plus cisplatin: A second, multi–center, study in Stage IIIB or IV NSCLC randomized 135 patients to Gemzar 1250 mg/m² on Days 1 and 8, and cisplatin 100 mg/m² on Day 1 of a 21–day cycle or to etoposide 100 mg/m² I.V. on Days 1, 2, and 3 and cisplatin 100 mg/m² on Day 1 of a 21–day cycle (Table 5).
There was no significant difference in survival between the two treatment arms (Log rank p=0.18, two–sided). The median survival was 8.7 months for the Gemzar plus cisplatin arm versus 7.0 months for the etoposide plus cisplatin arm. Median time to disease progression for the Gemzar plus cisplatin arm was 5.0 months compared to 4.1 monthson the etoposide plus cisplatin arm (Log rank p=0.015, two–sided). The objective response rate for the Gemzar plus cisplatin arm was 33% compared to 14% on the etoposide plus cisplatin arm (Fisher’s Exact p=0.01, two–sided).
Quality of Life (QOL): QOL was a secondary endpoint in both randomized studies. In the Gemzar plus cisplatin versus cisplatin study, QOL was measured using the FACT–L, which assessed physical, social, emotional and functional well–being, and lung cancer symptoms. In the study of Gemzar plus cisplatin versus etoposide plus cisplatin, QOL was measured using the EORTC QLQ–C30 and LC13, which assessed physical and psychological functioning and symptoms related to both lung cancer and its treatment. In both studies no significant differences were observed in QOL between the Gemzar plus cisplatin arm and the comparator arm.
Figure 3: Kaplan–Meier Survival Curve in Gemzar Plus Cisplatin Versus Cisplatin NSCLC Study (N=522).

Table 5: Randomized Trials of Combination Therapy With Gemzar Plus Cisplatin in NSCLC
N/A Not applicable
Trial	28–day Schedule28–day schedule — Gemzar plus cisplatin: Gemzar 1000 mg/m² on Days 1, 8, and 15 and cisplatin 100 mg/m² on Day 1 every 28 days; Single–agent cisplatin: cisplatin 100 mg/m² on Day 1 every 28 days.			21–day Schedule21–day schedule — Gemzar plus cisplatin: Gemzar 1250 mg/m² on Days 1 and 8 and cisplatin 100 mg/m² on Day 1 every 21 days; Etoposide plus Cisplatin: cisplatin 100 mg/m² on Day 1 and I.V. etoposide 100 mg/m² on Days 1, 2, and 3 every 21 days.
Treatment Arm	Gemzar/ Cisplatin	Cisplatin		Gemzar/ Cisplatin	Cisplatin/ Etoposide
Number of patients	260	262		69	66
Male	182	186		64	61
Female	78	76		5	5
Median age, years	62	63		58	60
Range	36 to 88	35 to 79		33 to 76	35 to 75
Stage IIIA	7%	7%		N/A	N/A
Stage IIIB	26%	23%		48%	52%
Stage IV	67%	70%		52%	49%
Baseline KPSKarnofsky Performance Status. 70 to 80	41%	44%		45%	52%
Baseline KPS 90 to 100	57%	55%		55%	49%

Survival			p=0.008			p=0.18
Median, months	9.0	7.6		8.7	7.0
(95%, C.I.) months	8.2, 11.0	6.6, 8.8		7.8, 10.1	6.0, 9.7
Time to Disease Progression			p=0.009			p=0.015
Median, months	5.2	3.7		5.0	4.1
(95%, C.I.) months	4.2, 5.7	3.0, 4.3		4.2, 6.4	2.4, 4.5
Tumor Response	26%	10%	p<0.0001p–value for tumor response was calculated using the two–sided Fisher’s Exact test for difference in binomial proportions. All other p–values were calculated using the Log rank test for difference in overall time to an event.	33%	14%	p=0.01

Pancreatic Cancer

Data from 2 clinical trials evaluated the use of Gemzar in patients with locally advanced or metastatic pancreatic cancer. The first trial compared Gemzar to 5–Fluorouracil (5–FU) in patients who had received no prior chemotherapy. A second trial studied the use of Gemzar in pancreatic cancer patients previously treated with 5–FU or a 5–FU–containing regimen. In both studies, the first cycle of Gemzar was administered intravenously at a dose of 1000 mg/m² over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitated holding a dose) followed by a week of rest from treatment with Gemzar. Subsequent cycles consisted of injections once weekly for 3 consecutive weeks out of every 4 weeks.
The primary efficacy parameter in these studies was“clinical benefit response,” which is a measure of clinical improvement based on analgesic consumption, pain intensity, performance status, and weight change. Definitions for improvement in these variables were formulated prospectively during the design of the 2 trials. A patient was considered a clinical benefit responder if either:

the patient showed a ≥50% reduction in pain intensity (Memorial Pain Assessment Card) or analgesic consumption, or a 20–point or greater improvement in performance status (Karnofsky Performance Status) for a period of at least 4 consecutive weeks, without showing any sustained worsening in any of the other parameters. Sustained worsening was defined as 4 consecutive weeks with either any increase in pain intensity or analgesic consumption or a 20–point decrease in performance status occurring during the first 12 weeks of therapy.
OR:
the patient was stable on all of the aforementioned parameters, and showed a marked, sustained weight gain (≥7% increase maintained for ≥4 weeks) not due to fluid accumulation.

The first study was a multi–center (17 sites in US and Canada), prospective, single–blinded, two–arm, randomized, comparison of Gemzar and 5–FU in patients with locally advanced or metastatic pancreatic cancer who had received no prior treatment with chemotherapy. 5–FU was administered intravenously at a weekly dose of 600 mg/m² for 30 minutes. The results from this randomized trial are shown in Table 6. Patients treated with Gemzar had statistically significant increases in clinical benefit response, survival, and time to disease progression compared to 5–FU. The Kaplan–Meier curve for survival is shown in Figure 4. No confirmed objective tumor responses were observed with either treatment.

Table 6: Gemzar Versus 5–FU in Pancreatic Cancer
	Gemzar	5–FU
Number of patients	63	63
Male	34	34
Female	29	29
Median age	62 years	61 years
Range	37 to 79	36 to 77
Stage IV disease	71.4%	76.2%
Baseline KPSKarnofsky Performance Status.≤70	69.8%	68.3%

Clinical benefit response	22.2% (NN=number of patients.=14)	4.8% (N=3)	p=0.004The p-value for clinical benefit response was calculated using the two-sided test for difference in binomial proportions. All other p-values were calculated using the Log rank test for difference in overall time to an event.
Survival			p=0.0009
Median	5.7 months	4.2 months
6–month probabilityKaplan-Meier estimates.	(N=30) 46%	(N=19) 29%
9–month probability	(N=14) 24%	(N=4) 5%
1–year probability	(N=9) 18%	(N=2) 2%
Range	0.2 to 18.6 months	0.4 to 15.1+No progression at last visit; remains alive. months
95% C.I. of the median	4.7 to 6.9 months	3.1 to 5.1 months
Time to Disease Progression			p=0.0013
Median	2.1 months	0.9 months
Range	0.1+ to 9.4 months	0.1 to 12.0+ months
95% C.I. of the median	1.9 to 3.4 months	0.9 to 1.1 months

Clinical benefit response was achieved by 14 patients treated with Gemzar and 3 patients treated with 5–FU. One patient on the Gemzar arm showed improvement in all 3 primary parameters (pain intensity, analgesic consumption, and performance status). Eleven patients on the Gemzar arm and 2 patients on the 5–FU arm showed improvement in analgesic consumption and/or pain intensity with stable performance status. Two patients on the Gemzar arm showed improvement in analgesic consumption or pain intensity with improvement in performance status. One patient on the 5–FU arm was stable with regard to pain intensity and analgesic consumption with improvement in performance status. No patient on either arm achieved a clinical benefit response based on weight gain.
Figure 4: Kaplan–Meier Survival Curve. The second trial was a multi–center (17 US and Canadian centers), open–label study of Gemzar in 63 patients with advanced pancreatic cancer previously treated with 5–FU or a 5–FU–containing regimen. The study showed a clinical benefit response rate of 27% and median survival of 3.9 months.

Other Clinical Studies

When Gemzar was administered more frequently than once weekly or with infusions longer than 60 minutes, increased toxicity was observed. Results of a Phase 1 study of Gemzar to assess the maximum tolerated dose (MTD) on a daily x 5 schedule showed that patients developed significant hypotension and severe flu–like symptoms that were intolerable at doses above 10 mg/m². The incidence and severity of these events were dose–related. Other Phase 1 studies using a twice–weekly schedule reached MTDs of only 65 mg/m² (30–minute infusion) and 150 mg/m² (5–minute bolus). The dose–limiting toxicities were thrombocytopenia and flu–like symptoms, particularly asthenia. In a Phase 1 study to assess the maximum tolerated infusion time, clinically significant toxicity, defined as myelosuppression, was seen with weekly doses of 300 mg/m² at or above a 270–minute infusion time. The half–life of gemcitabine is influenced by the length of the infusion (see CLINICAL PHARMACOLOGY) and the toxicity appears to be increased if Gemzar is administered more frequently than once weekly or with infusions longer than 60 minutes (see WARNINGS).

INDICATIONS AND USAGE

Therapeutic Indications

CONTRAINDICATION

WARNINGS

PRECAUTIONS

General

Laboratory Tests

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Nursing Mothers

It is not known whether Gemzar or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions from Gemzar in nursing infants, the mother should be warned and a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother and the potential risk to the infant.

Elderly Patients

Gemzar clearance is affected by age (see CLINICAL PHARMACOLOGY). There is no evidence, however, that unusual dose adjustments (i.e., other than those already recommended in the DOSAGE AND ADMINISTRATION section) are necessary in patients over 65, and in general, adverse reaction rates in the single–agent safety database of 979 patients were similar in patients above and below 65. Grade 3/4 thrombocytopenia was more common in the elderly. In the randomized clinical trial of Gemzar in combination with carboplatin for recurrent ovarian cancer (see CLINICAL STUDIES), 125 women treated with Gemzar plus carboplatin were <65 years and 50 were ≥65 years. Similar effectiveness was observed between older and younger women. There was significantly higher Grade 3/4 neutropenia in women 65 years of age or older. Overall, there were no substantial differences in toxicity profile of Gemzar plus carboplatin based on age.

Gender

Gemzar clearance is affected by gender (see CLINICAL PHARMACOLOGY). In the single–agent safety database (N=979 patients), however, there is no evidence that unusual dose adjustments (i.e., other than those already recommended in the DOSAGE AND ADMINISTRATION section) are necessary in women. In general, in single–agent studies of Gemzar, adverse reaction rates were similar in men and women, but women, especially older women, were more likely not to proceed to a subsequent cycle and to experience Grade 3/4 neutropenia and thrombocytopenia.

Pediatric Patients

The effectiveness of Gemzar in pediatric patients has not been demonstrated. Gemzar was evaluated in a Phase 1 trial in pediatric patients with refractory leukemia and determined that the maximum tolerated dose was 10 mg/m²/min for 360 minutes three times weekly followed by a one week rest period. Gemzar was also evaluated in a Phase 2 trial in patients with relapsed acute lymphoblastic leukemia (22 patients) and acute myelogenous leukemia (10 patients) using 10 mg/m²/min for 360 minutes three times weekly followed by a one week rest period. Toxicities observed included bone marrow suppression, febrile neutropenia, elevation of serum transaminases, nausea, and rash/desquamation, which were similar to those reported in adults. No meaningful clinical activity was observed in this Phase 2 trial.

Patients with Renal or Hepatic Impairment

Gemzar should be used with caution in patients with preexisting renal impairment or hepatic insufficiency as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations. Administration of Gemzar in patients with concurrent liver metastases or a pre–existing medical history of hepatitis, alcoholism, or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency.

Drug Interactions

Radiation Therapy

ADVERSE REACTIONS

OVERDOSAGE

There is no known antidote for overdoses of Gemzar. Myelosuppression, paresthesias, and severe rash were the principal toxicities seen when a single dose as high as 5700 mg/m² was administered by I.V. infusion over 30 minutes every 2 weeks to several patients in a Phase 1 study. In the event of suspected overdose, the patient should be monitored with appropriate blood counts and should receive supportive therapy, as necessary.

DOSAGE AND ADMINISTRATION

Adults

Instructions for Use/Handling

The recommended diluent for reconstitution of Gemzar is 0.9% Sodium Chloride Injection without preservatives. Due to solubility considerations, the maximum concentration for Gemzar upon reconstitution is 40 mg/mL. Reconstitution at concentrations greater than 40 mg/mL may result in incomplete dissolution, and should be avoided.
To reconstitute, add 5 mL of 0.9% Sodium Chloride Injection to the 200–mg vial or 25 mL of 0.9% Sodium Chloride Injection to the 1–g vial. Shake to dissolve. These dilutions each yield a gemcitabine concentration of 38 mg/mL which includes accounting for the displacement volume of the lyophilized powder (0.26 mL for the 200–mg vial or 1.3 mL for the 1–g vial). The total volume upon reconstitution will be 5.26 mL or 26.3 mL, respectively. Complete withdrawal of the vial spans will provide 200 mg or 1 g of gemcitabine, respectively. The appropriate amount of drug may be administered as prepared or further diluted with 0.9% Sodium Chloride Injection to concentrations as low as 0.1 mg/mL.
Reconstituted Gemzar is a clear, colorless to light straw–colored solution. After reconstitution with 0.9% Sodium Chloride Injection, the pH of the resulting solution lies in the range of 2.7 to 3.3. The solution should be inspected visually for particulate matter and discoloration, prior to administration, whenever solution or container permit. If particulate matter or discoloration is found, do not administer.
When prepared as directed, Gemzar solutions are stable for 24 hours at controlled room temperature 20° to 25°C (68° to 77°F) [See USP]. Discard unused portion. Solutions of reconstituted Gemzar should not be refrigerated, as crystallization may occur.
The compatibility of Gemzar with other drugs has not been studied. No incompatibilities have been observed with infusion bottles or polyvinyl chloride bags and administration sets.
Unopened vials of Gemzar are stable until the expiration date indicated on the package when stored at controlled room temperature 20° to 25°C (68° to 77°F) [See USP].
Caution should be exercised in handling and preparing Gemzar solutions. The use of gloves is recommended. If Gemzar solution contacts the skin or mucosa, immediately wash the skin thoroughly with soap and water or rinse the mucosa with copious amounts of water. Although acute dermal irritation has not been observed in animal studies, 2 of 3 rabbits exhibited drug–related systemic toxicities (death, hypoactivity, nasal discharge, shallow breathing) due to dermal absorption.
Procedures for proper handling and disposal of anti–cancer drugs should be considered. Several guidelines on this subject have been published.^1–8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

HOW SUPPLIED

REFERENCES

Recommendations for the safe handling of parenteral antineoplastic drugs. NIH publication No. 83–2621. US Government Printing Office, Washington, DC 20402.
Council on Scientific Affairs: Guidelines for handling parenteral antineoplastics. JAMA 1985;253:1590.
National Study Commission on Cytotoxic Exposure — Recommendations for handling cytotoxic agents, 1987. Available from Louis P Jeffrey, ScD, Director of Pharmacy Services, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02902.
Clinical Oncological Society of Australia: Guidelines and recommendations for safe handling of antineoplastic agents. Med J Aust 1983;1:426.
Jones RB, et al. Safe handling of chemotherapeutic agents: A report from the Mount Sinai Medical Center. CA 1983;33(Sept/Oct):258.
American Society of Hospital Pharmacists: Technical assistance bulletin on handling cytotoxic drugs in hospitals. Am J Hosp Pharm 1990;47:1033.
Controlling Occupational Exposure to Hazardous Drugs, OSHA Work Practice Guidelines. Am J Health–Sys Pharm 1996;53:1669–1685.
ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 1999:32–41.

Literature revised July 14, 2006
Eli Lilly and Company
Indianapolis, IN 46285, USA
Copyright © 1996, 2006, Eli Lilly and Company. All rights reserved.

DEXTROAMPHETAMINE SACCHARATE,AMPHETAMINE ASPARTATE MONOHYDRATE,DEXTROAMPHETAMINE SULFATE ANDAMPHETAMINE SULFATE TABLETSCII5 mg, 10 mg, 20 mg and 30 mg(Mixed Salts of a Single-Entity Amphetamine Product)Rx only

2011-06-12T00:11:00.003-07:00

DEXTROAMPHETAMINE SACCHARATE,
AMPHETAMINE ASPARTATE MONOHYDRATE,
DEXTROAMPHETAMINE SULFATE AND
AMPHETAMINE SULFATE TABLETS
CII
5 mg, 10 mg, 20 mg and 30 mg
(Mixed Salts of a Single-Entity Amphetamine Product)

Rx only

AMPHETAMINES HAVE A HIGH POTENTIAL FOR ABUSE. ADMINISTRATION OF AMPHETAMINES FOR PROLONGED PERIODS OF TIME MAY LEAD TO DRUG DEPENDENCE AND MUST BE AVOIDED. PARTICULAR ATTENTION SHOULD BE PAID TO THE POSSIBILITY OF SUBJECTS OBTAINING AMPHETAMINES FOR NON-THERAPEUTIC USE OR DISTRIBUTION TO OTHERS, AND THE DRUGS SHOULD BE PRESCRIBED OR DISPENSED SPARINGLY.
MISUSE OF AMPHETAMINE MAY CAUSE SUDDEN DEATH AND SERIOUS CARDIOVASCULAR ADVERSE EVENTS.

DESCRIPTION

Amphetamines are sympathomimetic amines. A single-entity amphetamine product combining the neutral sulfate salts of dextroamphetamine and amphetamine, with the dextro isomer of amphetamine saccharate and d, l-amphetamine aspartate monohydrate.

EACH TABLET CONTAINS:	5 mg	10 mg	20 mg	30 mg
Dextroamphetamine
Saccharate……………………………...	1.25 mg	2.5 mg	5 mg	7.5 mg
Amphetamine
Aspartate Monohydrate ……...………..	1.25 mg	2.5 mg	5 mg	7.5 mg
Dextroamphetamine
Sulfate USP………………………….	1.25 mg	2.5 mg	5 mg	7.5 mg
Amphetamine
Sulfate USP…………………………....	1.25 mg	2.5 mg	5 mg	7.5 mg
Total amphetamine
base equivalence ………………………	3.13 mg	6.3 mg	12.6 mg	18.8 mg

In addition, each tablet for oral administration contains the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose and pregelatinized starch.
Colors: 5 mg and 10 mg tablets contain FD&C Blue #2 Aluminum Lake
20 mg and 30 mg tablets contain D&C Red #27 Aluminum Lake as a color additive

CLINICAL PHARMACOLOGY

Pharmacodynamics

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known. Amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

Pharmacokinetics

Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate tablets contain d-amphetamine and l-amphetamine salts in the ratio of 3:1. Following administration of a single dose 10 or 30 mg of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate tablets to healthy volunteers under fasted conditions, peak plasma concentrations occurred approximately 3 hours post-dose for both d-amphetamine and l-amphetamine. The mean elimination half-life (t_1/2) for d-amphetamine was shorter than the t_1/2 of the l-isomer (9.77-11 hours vs. 11.5-13.8 hours). The PK parameters (C_max, AUC_0-inf) of d-and l-amphetamine increased approximately three-fold from 10 mg to 30 mg indicating dose-proportional pharmacokinetics.
The effect of food on the bioavailability of dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate has not been studied.

INDICATIONS AND USAGE

Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate tablets are indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and Narcolepsy.

Attention Deficit Hyperactivity Disorder (ADHD)

A diagnosis of Attention Deficit Hyperactivity Disorder (ADHD; DSM-IV^®) implies the presence of hyperactive-impulsive or inattentive symptoms that caused impairment and were present before age 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning, and be present in two or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the Inattentive Type, at least six of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor ulener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least six of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; "on the go;" excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.

CONTRAINDICATIONS

Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma.
Agitated states.
Patients with a history of drug abuse.
During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result.)

WARNINGS

Serious Cardiovascular Events

Sudden Death and Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems

Psychiatric Adverse Events

Long-Term Suppression of Growth

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturaulic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they will likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining weight as expected may need to have their treatment interrupted.

Seizures

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizure, in patients with prior EEG abnormalities in absence of seizures, and very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Visual Disturbance

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

PRECAUTIONS

Geriatric Use: Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate tablets have not been studied in the geriatric population.

ADVERSE REACTIONS

DRUG ABUSE AND DEPENDENCE

Dextroamphetamine sulfate, amphetamine sulfate, amphetamine aspartate monohydrate, and dextroamphetamine saccharate are Schedule II controlled substance.
Amphetamines have been extensively abused. Tolerance, extreme psychological dependence, and severe social disability have occurred. There are reports of patients who have increased the dosage to many times higher than recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG. Manifestations of chronic intoxication with amphetamines include severe dermatoses, marked insomnia, irritability, hyperactivity, and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia.

OVERDOSAGE

Individual patient response to amphetamines varies widely. Toxic symptoms may occur idiosyncratically at low doses.

DOSAGE AND ADMINISTRATION

Regardless of indication, amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted according to the therapeutic needs and response of the patient. Late evening doses should be avoided because of the resulting insomnia.

HOW SUPPLIED

Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate tablets 5 mg, 10 mg, 20 mg, and 30 mg.
Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate tablets 5 mg: Blue, round, compressed tablets, debossed cor over 130 on one side and Quadrisect on the other side.
In bottles of 100 tablets (NDC 64720-130-10)
In bottles of 500 tablets (NDC 64720-130-50)
In bottles of 1000 tablets (NDC 64720-130-11)
Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate tablets 10 mg: Blue, round, compressed tablets, debossed cor over 132 on one side and Quadrisect on the other side.
In bottles of 100 tablets (NDC 64720-132-10)
In bottles of 500 tablets (NDC 64720-132-50)
In bottles of 1000 tablets (NDC 64720-132-11)
Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate tablets 20 mg: Pink, round, compressed tablets, debossed cor over 135 on one side and Quadrisect on the other side.
In bottles of 100 tablets (NDC 64720-135-10)
In bottles of 500 tablets (NDC 64720-135-50)
In bottles of 1000 tablets (NDC 64720-135-11)
Dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate and amphetamine sulfate tablets 30 mg: Pink, round, compressed tablets, debossed cor over 136 on one side and Quadrisect on the other side.
In bottles of 100 tablets (NDC 64720-136-10)
In bottles of 500 tablets (NDC 64720-136-50)
In bottles of 1000 tablets (NDC 64720-136-11)
Dispense in a tight, light-resistant container as defined in the USP.
Store at 20° - 25°C (68° - 77°F). (See USP Controlled Room Temperature).
Protect from moisture.
MF # 177-01
Rev. June 2007
Manufactured and Distributed by:
Corepharma LLC
Middlesex, NJ 08846

Medication Guide for Dextroamphetamine Saccharte, Amphetamine Aspartate Monohydrate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets CII
(DEX-troe-am-FET-uh-meen SACK-uh-rate/ am-FET-uh-meen ass-PAR-tate MAH-no-HIGH-drate/ DEX-troe-am-FET-uh-meen SULL-fate/ am-FET-uh-meen SULL-fate)

Read the Medication Guide that comes with Dextroamphetamine Saccharate, Amphetamine Aspartate Monohydrate, Dextroamphetamine Sulfate, and Amphetamine Sulfate Tablets (Mixed Amphetamine Salts Tablets) before you or your child starts taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about you or your child’s treatment with Mixed Amphetamine Salts Tablets.

What is the most important information I should know about mixed amphetamine salts? The following have been reported with use of mixed amphetamine salts and other stimulant medicines.
1. Heart –related problems:

sudden death in patients who have heart problems or heart defects
stroke and heart attack in adults
increased blood pressure and heart rate

Tell your doctor if you or your child have any heart problems, heart defects, high blood pressure, or a family history of these problems.
Your doctor should check you or your child carefully for heart problems before starting mixed amphetamine salts.
Your doctor should check you or your child’s blood pressure and heart rate regularly during treatment with mixed amphetamine salts.
Call your doctor right away if you or your child has any signs of heart problems such as chest pain, shortness of breath, or fainting while taking Mixed Amphetamine Salts Tablets.
2. Mental (Psychiatric) problems:
All Patients

new or worse behavior and thought problems
new or worse bipolar illness
new or worse aggressive behavior or hostility

Children and Teenagers

new psychotic symptoms (such as hearing voices, believing things that are not true, are suspicious) or new manic symptoms

Tell your doctor about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression.
Call your doctor right away if you or your child have any new or worsening mental symptoms or problems while taking Mixed Amphetamine Salts Tablets, especially seeing or hearing things that are not real, believing things that are not real, or are suspicious.

What are mixed amphetamine salts?
Mixed amphetamine salts are central nervous system stimulant prescription medicine. They are used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Mixed amphetamine salts may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.
Mixed amphetamine salts should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.
Mixed amphetamine salts are also used in the treatment of a sleep disorder called narcolepsy.

Mixed amphetamine salts are a federally controlled substance (CII) because they can be abused or lead to dependence. Keep Mixed Amphetamine Salts Tablets in a safe place to prevent misuse and abuse. Selling or giving away Mixed Amphetamine Salts Tablets may harm others, and is against the law.Tell your doctor if you or your child have (or have a family history of) ever abused or been dependent on alcohol, prescription medicines or street drugs.

Who should not take mixed amphetamine salts?
Mixed amphetamine salts should not be taken if you or your child:

have heart disease or hardening of the arteries
have moderate to severe high blood pressure
have hyperthyroidism
have an eye problem called glaucoma
are very anxious, tense, or agitated
have a history of drug abuse
are taking or have taken within the past 14 days an anti-depression medicine called a monoamine oxidase inhibitor or MAOI
is sensitive to, allergic to, or had a reaction to other stimulant medicines

Mixed amphetamine salts are not recommended for use in children less than 3 years old.
Mixed amphetamine salts may not be right for you or your child. Before starting mixed amphetamine salts tell your or your child’s doctor about all health conditions (or a family history of) including:

heart problems, heart defects, high blood pressure
mental problems including psychosis, mania, bipolar illness, or depression
tics or Tourette’s syndrome
liver or kidney problems
thyroid problems
seizures or have had an abnormal brain wave test (EEG)

Tell your doctor if you or your child is pregnant, planning to become pregnant, or breastfeeding.
Can Mixed Amphetamine Salts Tablets be taken with other medicines?
Tell your doctor about all of the medicines that you or child take including prescription and nonprescription medicines, vitamins, and herbal supplements.
Mixed amphetamine salts and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking mixed amphetamine salts.
Your doctor will decide whether mixed amphetamine salts can be taken with other medicines.
Especially tell your doctor if you or your child takes:

anti-depression medicines including MAOIs
seizure medicines
blood thinner medicines
blood pressure medicines
stomach acid medicines
cold or allergy medicines that contain decongestants

Know the medicines that you or your child takes. Keep a ul of your medicines with you to show your doctor and pharmacist.
Do not start any new medicine while taking mixed amphetamine salts without talking to your doctor first.
How should Mixed Amphetamine Salts Tablets be taken?

Take Mixed Amphetamine Salts Tablets exactly as prescribed. Your doctor may adjust the dose until it is right for you or your child.
Mixed Amphetamine Salts Tablets are usually taken two to three times a day. The first dose is usually taken when you first wake in the morning. One or two more doses may be taken during the day, 4 to 6 hours apart.
Mixed Amphetamine Salts Tablets can be taken with or without food.
From time to time, your doctor may stop mixed amphetamine salts treatment for a while to check ADHD symptoms.
Your doctor may do regular checks of the blood, heart, and blood pressure while taking mixed amphetamine salts. Children should have their height and weight checked often while taking mixed amphetamine salts. Mixed amphetamine salt treatment may be stopped if a problem is found during these check-ups.
If you or your child takes too much mixed amphetamine salt or overdoses, call your doctor or poison control center right away, or get emergency treatment.

What are possible side effects of mixed amphetamine salts?
See “What is the most important information I should know about mixed amphetamine salts?”for information on reported heart and mental problems.
Other serious side effects include:

slowing of growth (height and weight) in children
seizures, mainly in patients with a history of seizures
eyesight changes or blurred vision

Common side effects include:

headache
stomach ache
trouble sleeping
decreased appetite
nervousness
dizziness

Mixed amphetamine salts may affect you or your child’s ability to drive or do other dangerous activities.
Talk to your doctor if you or your child has side effects that are bothersome or do not give away.This is not a complete ul of possible side effects. Ask your doctor or pharmacist for more information.
How should I store Mixed Amphetamine Salts Tablets?

Store in a safe place at 20° - 25° C (68° - 77° F). (See USP Controlled Room Temperature).
Protect from moisture.
Keep Mixed Amphetamine Salt Tablets and all medicines out of the reach of children.

General information about mixed amphetamine salts.
Medicines are sometimes prescribed for purpose other than those uled in a Medication Guide. Do not use mixed amphetamine salts for a condition for which it was not prescribed. Do not give mixed amphetamine salts to other people, even if they have the same condition. It may harm them and it against the law.
This Medication Guide summarizes the most important information about mixed amphetamine salts. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about mixed amphetamine salts that was written for healthcare professionals. For more information, you may also contact Corepharma (the maker of Mixed Amphetamine Salts) at 1-800-850-2719.
What are the ingredients in Mixed Amphetamines Salts Tablets?
Active Ingredients:dextroamphetamine saccharate, amphetamine aspartate monohydrate, dextroamphetamine sulfate USP, and amphetamine sulfate USP.
Inactive Ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, and pregelatinized starch.
Colors: Mixed Amphetamine Salts Tablets 5 mg and 10 mg contain FD&C Blue #2 Aluminum Lake
Mixed Amphetamine Salts Tablets 20 mg and 30 mg contain D&C Red #27 Aluminum Lake as a color additive.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
MF# 593-01
Rev. June 2007

DESMOPRESSIN ACETATE TABLETS

2011-06-12T00:11:00.001-07:00

DESMOPRESSIN ACETATE TABLETS

1002320102
Rx only

DESCRIPTION:

Desmopressin acetate are a synthetic analogue of the natural pituitary hormone 8-arginine vasopressin (ADH), is an antidiuretic hormone affecting renal water conservation. It is chemically defined as 1-(3-mercaptopropionic acid)-8-D-arginine vasopressin monoacetate (salt) trihydrate. The structural formula is as follows:
C₄₆H₆₄N₁₄O₁₂S₂·C₂H₄O₂·3H₂0 Molecular Weight: 1183.34 Desmopressin Acetate Tablets contain desmopressin acetate equivalent to either 0.1 mg or 0.2 mg of desmopressin acetate. In addition, each tablet contains the following inactive ingredients: butylated hydroxyanisole, butylated hydroxytoluene, crospovidone, lactose monohydrate, magnesium stearate, povidone and potato starch.

CLINICAL PHARMACOLOGY:

Desmopressin acetate tablets contain as active substance, desmopressin acetate, a synthetic analogue of the natural hormone arginine vasopressin.

Central Diabetes Insip idus:

Dose response studies in patients with diabetes insipidus have demonstrated that oral doses of 0.025 mg to 0.4 mg produced clinically significant antidiuretic effects. In most patients, doses of 0.1 mg to 0.2 mg produced optimal antidiuretic effects lasting up to eight hours. With doses of 0.4 mg, antidiuretic effects were observed for up to 12 hours; measurements beyond 12 hours were not recorded. Increasing oral doses produced dose dependent increases in the plasma levels of desmopressin acetate.
The plasma half-life of desmopressin acetate followed a monoexponential time course with t_1/2 values of 1.5 to 2.5 hours which was independent of dose.
The bioavailability of desmopressin acetate oral tablets is about 5% compared to intranasal desmopressin acetate, and about 0.16% compared to intravenous desmopressin acetate. The time to reach maximum plasma desmopressin acetate levels ranged from 0.9 to 1.5 hours following oral or intranasal administration, respectively. Following administration of desmopressin acetate tablets, the onset of antidiuretic effect occurs at around 1 hour, and it reaches a maximum at about 4 to 7 hours based on the measurement of increased urine osmolality.
The use of desmopressin acetate tablets in patients with an established diagnosis will result in a reduction in urinary output with an accompanying increase in urine osmolality. These effects usually will allow resumption of a more normal life style, with a decrease in urinary frequency and nocturia.
There are reports of an occasional change in response to the intranasal formulations of desmopressin acetate (desmopressin acetate Nasal Spray and desmopressin acetate Rhinal Tube). Usually, the change occurred over a period of time greater than six months. This change may be due to decreased responsiveness, or to shortened duration of effect. There is no evidence that this effect is due to the development of binding antibodies, but may be due to a local inactivation of the peptide. No lessening of effect was observed in the 46 patients who were treated with desmopressin acetate tablets for 12 to 44 months and no serum antibodies to desmopressin were detected.
The change in structure of arginine vasopressin to desmopressin acetate resulted in less vasopressor activity and decreased action on visceral smooth muscle relative to enhanced antidiuretic activity. Consequently, clinically effective antidiuretic doses are usually below the threshold for effects on vascular or visceral smooth muscle. In the four long-term studies of desmopressin acetate tablets, no increases in blood pressure in 46 patients receiving desmopressin acetate tablets for periods of 12 to 44 months were reported.
In one study, the pharmacodynamic characteristics of desmopressin acetate tablets and intranasal formulation were compared during an 8-hour dosing interval at steady state. The doses administered to 36 hydrated (water loaded) healthy male adult volunteers every 8 hours were 0.1, 0.2, 0.4 mg orally and 0.01 mg intranasally by rhinal tube. The results are shown in the following table:

Mean Changes from Baseline (SE) in Pharmacodynamic Parameters in Normal Healthy Adult Volunteers
(SE) = Standard error of the mean
Treatment	Total Urine Volume in mL	Maximum Urine Osmolality in mOsm/kg
0.1 mg PO q8h	-3689.3 (149.6)	514.8 (21.9)
0.2 mg PO q8h	-4429.9 (149.6)	686.3 (21.9)
0.4 mg PO q8h	-4998.8 (149.6)	769.3 (21.9)
0.01 mg IN q8h	-4844.9 (149.6)	754.1 (21.9)

With respect to the mean values of total urine volume decrease and maximum urine osmolality increase from baseline, the 90% confidence limits estimated that the 0.4 mg and 0.2 mg oral dose produced between 95% and 110% and 84% to 99% of pharmacodynamic activity, respectively, when compared to the 0.01 mg intranasal dose.
While both the 0.2 mg and 0.4 mg oral doses are considered pharmacodynamically similar to the 0.01 mg intranasal dose, the pharmacodynamic data on an inter-subject basis was highly variable and, therefore, individual dosing is recommended.
In another study in diabetes insipidus patients, the pharmacodynamic characteristics of desmopressin acetate tablets and intranasal formulations were compared over a 12-hour period. Ten fluid-controlled patients under age 18 were administered tablet doses of 0.2 mg and 0.4 mg, and intranasal doses of 0.01 mg and 0.02 mg.

Mean Peak Pharmacodynamic Parameters (SD) in Pediatric and Adolescent Diabetes Insipidus Patients
(SD) = Standard Deviation
Treatment	Total Urine Volume in mL/min	Maximum Urine Osmolality in mOsm/kg
0.1 mg IN	0.3 (0.15)	717.0 (224.63)
0.2 mg IN	0.3 (0.25)	761.8 (298.82)
0.4 mg PO	0.3 (0.12)	678.3 (147.91)
0.01 mg PO	0.2 (0.15)	787.2 (73.34)

All four dose formulations (0.01 mg IN, 0.02 mg IN, 0.2 mg PO and 0.4 mg PO) have a similar, pronounced pharmacodynamic effect on urine volume and urine osmolality. At two hours after study drug administration, mean urine volume was 4 mL/min and urine osmolality was >500 mOsm/kg. Mean plasma osmolality remained relatively constant over the time course recorded (0 to 12 hours). A statistical separation from baseline did not occur at any dose or time point. In these patients, the 0.2 mg tablets and the 0.01 mg intranasal spray exhibited similar pharmacodynamic profiles as did the 0.4 mg tablets and the 0.02 mg intranasal spray formulation. In another study of adult diabetes insipidus patients previously controlled on desmopressin acetate intranasal spray, after one week of self-titration from spray to tablets, patients’ diuresis was controlled with 0.1 mg desmopressin acetate tablets three times a day.

Primary Nocturnal Enuresis:

Two double-blind, randomized, placebo-controlled studies were conducted in 340 patients with primary nocturnal enuresis. Patients were 5-17 years old, and 72% were males. A total of 329 patients were evaluated for efficacy. Patients were evaluated over a two-week baseline period in which the average number of wet nights was 10 (range 4-14). Patients were then randomized to receive 0.2, 0.4, or 0.6 mg of desmopressin acetate or placebo. The pooled results after two weeks are shown in the following table:

Response to Desmopressin Acetate and Placebo at Two Weeks of Treatment Mean (SE) Number of Wet Nights/2 Weeks
	Placebo (n=85)	0.2 mg/day (n=79)	0.4 mg/day (n=82)	0.6 mg/day (n=83)
Baseline	10 (0.3)	11 (0.3)	10 (0.3)	10(0.3)
Reduction from Baseline	1 (0.3)	3 (0.4)	3 (0.4)	4 (0.4)
Percent Reduction from Baseline	10%	27%	30%	40%
p-value vs. placebo	─	<0.05	<0.05	<0.05

Patients treated with desmopressin acetate tablets showed a statistically significant reduction in the number of wet nights compared to placebo-treated patients. A greater response was observed with increasing doses up to 0.6 mg.
In a six month, open-label extension study, patients completing the placebo-controlled studies were started on 0.2 mg/day desmopressin acetate tablets, and the dose was progressively increased until the optimal response was achieved (maximum dose 0.6 mg/day). A total of 230 patients were evaluated for efficacy; the average number of wet nights/2 weeks during the untreated baseline period was 10 (range 4-14), and the average duration (SD) of treatment was 4.2 (1.8) months. Twenty-five (25) patients (11%) achieved a complete or near complete response (≤2 wet nights/2 weeks) and did not require titration to the 0.6 mg/day dose. The majority of patients (198 of 230, 86%) were titrated to the highest dose. When all dose groups were combined, 128 (56%) showed at least a 50% reduction from baseline in the number of wet nights/2 weeks, while 87 (38%) patients achieved a complete or near complete response.

INDICATIONS AND USAGE:

Central Diabetes Insipidus:

Desmopressin acetate tablets are indicated as antidiuretic replacement therapy in the management of central diabetes insipidus and for the management of the temporary polyuria and polydipsia following head trauma or surgery in the pituitary region. Desmopressin acetate tablets are ineffective for the treatment of nephrogenic diabetes insipidus.
Patients were selected for therapy based on the diagnosis by means of the water deprivation test, the hypertonic saline infusion test, and/or response to antidiuretic hormone. Continued response to desmopressin acetate can be monitored by measuring urine volume and osmolality.

Primary Nocturnal Enuresis:

Desmopressin acetate tablets are indicated for the management of primary nocturnal enuresis. Desmopressin acetate tablets may be used alone or as an adjunct to behavioral conditioning or other non-pharmacologic intervention.

CONTRAINDICATIONS:

Desmopressin acetate tablets are contraindicated in individuals with known hypersensitivity to desmopressin acetate or to any of the components of this product.

WARNINGS:

When desmopressin acetate tablets are administered, in particular in pediatric and geriatric patients, fluid intake should be adjusted downward to decrease the potential occurrence of water intoxication and hyponatremia with accompanying signs and symptoms (headache, nausea/vomiting, decreased serum sodium and weight gain). Particular attention should be paid to the possibility of the rare occurrence of an extreme decrease in plasma osmolality that may result in seizures which could lead to coma.

PRECAUTIONS:

General:

Intranasal formulations of desmopressin acetate at high doses and desmopressin acetate injection have infrequently produced a slight elevation of blood pressure which disappears with a reduction of dosage. Although this effect has not been observed when single oral doses up to 0.6 mg have been administered, the drug should be used with caution in patients with coronary artery insufficiency and/or hypertensive cardiovascular disease, because of a possible rise in blood pressure.
Desmopressin acetate should be used with caution in patients with conditions associated with fluid and electrolyte imbalance, such as cystic fibrosis, since these patients may develop hyponatremia.
Rare severe allergic reactions have been reported with desmopressin acetate. Anaphylaxis has been reported with intravenous and intranasal administration of desmopressin acetate, but not with desmopressin acetate tablets.

Laboratory Tests:

Drug Interactions:

Although the pressor activity of desmopressin acetate is very low compared to its antidiuretic activity, large doses of desmopressin acetate tablets should be used with other pressor agents only with careful patient monitoring.

Carcinogenicity, Mutagenicity, and Impairment of Fertility:

Studies with desmopressin acetate have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

Pregnancy:

Category B:
Fertility studies have not been done. Teratology studies in rats and rabbits at doses from 0.05 to 10 µg/kg/day (approximately 0.1 times the maximum systemic human exposure in rats and up to 38 times the maximum systemic human exposure in rabbits based on surface area, mg/m²) revealed no harm to the fetus due to desmopressin acetate. There are, however, no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Several publications where desmopressin acetate was used in the management of diabetes insipidus during pregnancy are available; these include a few anecdotal reports of congenital anomalies and low birth weight babies. However, no causal connection between these events and desmopressin acetate has been established. A fifteen year Swedish epidemiologic study of the use of desmopressin acetate in pregnant women with diabetes insipidus found the rate of birth defects to be no greater than that in the general population; however, the statistical power of this study is low. As opposed to preparations containing natural hormones, desmopressin acetate in antidiuretic doses has no uterotonic action and the physician will have to weigh the possible therapeutic advantages against the possible risks in each case.

Nursing Mothers:

There have been no controlled studies in nursing mothers. A single study in postpartum women demonstrated a marked change in plasma, but little if any change in assayable desmopressin acetate in breast milk following an intranasal dose of 0.01 mg.
It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when desmopressin acetate is administered to nursing mothers.

Pediatric Use:

ADVERSE REACTIONS:

Infrequently, large doses of the intranasal formulations of desmopressin acetate and desmopressin acetate injection have produced transient headache, nausea, flushing and mild abdominal cramps. These symptoms have disappeared with reduction in dosage.

Central Diabetes Insipidus:

In long-term clinical studies in which patients with diabetes insipidus were followed for periods up to 44 months of desmopressin acetate tablet therapy, transient increases in AST (SGOT) no higher than 1.5 times the upper limit of normal were occasionally observed. Elevated AST (SGOT) returned to the normal range despite continued use of desmopressin acetate tablets.

Primary Nocturnal Enuresis:

The only adverse event occurring in ≥ 3% of patients in controlled clinical trials with desmopressin acetate tablets that was probably, possibly, or remotely related to study drug was headache (4% desmopressin acetate, 3% placebo).

Other:

The following adverse events have been reported; however, their relationship to desmopressin acetate has not been established: abnormal thinking, diarrhea, and edema-weight gain.
See WARNINGS for the possibility of water intoxication and hyponatremia.

Overdosage:

(See ADVERSE REACTIONS.) In case of overdose, the dose should be reduced, frequency of administration decreased, or the drug withdrawn according to the severity of the condition. There is no known specific antidote for desmopressin acetate. The patient should be observed and treated with appropriate symptomatic therapy.
An oral LD₅₀ has not been established. Oral doses up to 0.2 mg/kg/day have been administered to dogs and rats for 6 months without any significant drug-related toxicities reported. An intravenous dose of 2 mg/kg in mice demonstrated no effect.

DOSAGE AND ADMINISTRATION:

Central Diabetes Insipidus:

The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to the diurnal pattern of response. Response should be estimated by two parameters: adequate duration of sleep and adequate, not excessive, water turnover. Patients previously on intranasal desmopressin acetate therapy should begin tablet therapy twelve hours after the last intranasal dose. During the initial dose titration period, patients should be observed closely and appropriate safety parameters measured to assure adequate response. Patients should be monitored at regular intervals during the course of desmopressin acetate tablet therapy to assure adequate antidiuretic response. Modifications in dosage regimen should be implemented as necessary to assure adequate water turnover.

Primary Nocturnal Enuresis:

The dosage of desmopressin acetate tablets must be determined for each individual patient and adjusted according to response. Patients previously on intranasal desmopressin acetate therapy can begin tablet therapy the night following (24 hours after) the last intranasal dose. The recommended initial dose for patients age 6 years and older is 0.2 mg at bedtime. The dose may be titrated up to 0.6 mg to achieve the desired response.

HOW SUPPLIED:

Desmopressin Acetate Tablets are available as:

0.1 mg	White, oval, flat-faced, beveled-edge scored tablet. Debossed with stylized Barr on one side and 232/0.1 on the scored side. Available in bottles of:
	100 Tablets	NDC 0555-0232-02
0.2 mg	White, oval, flat-faced, beveled-edge scored tablet. Debossed with stylized Barr on one side and 233/0.2 on the scored side. Available in bottles of:
	100 Tablets	NDC 0555-0233-02
	250 Tablets	NDC 0555-0233-03

Dispense in a tight, light-resistant container with a child-resistant closure.
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Avoid exposure to excessive heat or light.
Keep out of the reach of children.

MANUFACTURED BY
BARR LABORATORIES, INC.
Pomona, NY 10970
MARCH 2005
BR-232, 233

DEPAKOTE® Sprinkle Capsules (divalproex sodium coated particlesin capsules)

2011-06-12T00:10:00.003-07:00

DEPAKOTE® Sprinkle Capsules
(divalproex sodium coated particles in capsules)

BOX WARNING
HEPATOTOXICITY:
HEPATIC FAILURE RESULTING IN FATALITIES HAS OCCURRED IN PATIENTS RECEIVING VALPROIC ACID AND ITS DERIVATIVES. EXPERIENCE HAS INDICATED THAT CHILDREN UNDER THE AGE OF TWO YEARS ARE AT A CONSIDERABLY INCREASED RISK OF DEVELOPING FATAL HEPATOTOXICITY, ESPECIALLY THOSE ON MULTIPLE ANTICONVULSANTS, THOSE WITH CONGENITAL METABOLIC DISORDERS, THOSE WITH SEVERE SEIZURE DISORDERS ACCOMPANIED BY MENTAL RETARDATION, AND THOSE WITH ORGANIC BRAIN DISEASE. WHEN DEPAKOTE IS USED IN THIS PATIENT GROUP, IT SHOULD BE USED WITH EXTREME CAUTION AND AS A SOLE AGENT. THE BENEFITS OF THERAPY SHOULD BE WEIGHED AGAINST THE RISKS. ABOVE THIS AGE GROUP, EXPERIENCE IN EPILEPSY HAS INDICATED THAT THE INCIDENCE OF FATAL HEPATOTOXICITY DECREASES CONSIDERABLY IN PROGRESSIVELY OLDER PATIENT GROUPS.
THESE INCIDENTS USUALLY HAVE OCCURRED DURING THE FIRST SIX MONTHS OF TREATMENT. SERIOUS OR FATAL HEPATOTOXICITY MAY BE PRECEDED BY NON-SPECIFIC SYMPTOMS SUCH AS MALAISE, WEAKNESS, LETHARGY, FACIAL EDEMA, ANOREXIA, AND VOMITING. IN PATIENTS WITH EPILEPSY, A LOSS OF SEIZURE CONTROL MAY ALSO OCCUR. PATIENTS SHOULD BE MONITORED CLOSELY FOR APPEARANCE OF THESE SYMPTOMS. LIVER FUNCTION TESTS SHOULD BE PERFORMED PRIOR TO THERAPY AND AT FREQUENT INTERVALS THEREAFTER, ESPECIALLY DURING THE FIRST SIX MONTHS.
TERATOGENICITY:
VALPROATE CAN PRODUCE TERATOGENIC EFFECTS SUCH AS NEURAL TUBE DEFECTS (E.G., SPINA BIFIDA). ACCORDINGLY, THE USE OF VALPROATE PRODUCTS IN WOMEN OF CHILDBEARING POTENTIAL REQUIRES THAT THE BENEFITS OF ITS USE BE WEIGHED AGAINST THE RISK OF INJURY TO THE FETUS. THIS IS ESPECIALLY IMPORTANT WHEN THE TREATMENT OF A SPONTANEOUSLY REVERSIBLE CONDITION NOT ORDINARILY ASSOCIATED WITH PERMANENT INJURY OR RISK OF DEATH (E.G., MIGRAINE) IS CONTEMPLATED. SEE WARNINGS, INFORMATION FOR PATIENTS.
AN INFORMATION SHEET DESCRIBING THE TERATOGENIC POTENTIAL OF VALPROATE IS AVAILABLE FOR PATIENTS.
PANCREATITIS:
CASES OF LIFE-THREATENING PANCREATITIS HAVE BEEN REPORTED IN BOTH CHILDREN AND ADULTS RECEIVING VALPROATE. SOME OF THE CASES HAVE BEEN DESCRIBED AS HEMORRHAGIC WITH A RAPID PROGRESSION FROM INITIAL SYMPTOMS TO DEATH. CASES HAVE BEEN REPORTED SHORTLY AFTER INITIAL USE AS WELL AS AFTER SEVERAL YEARS OF USE. PATIENTS AND GUARDIANS SHOULD BE WARNED THAT ABDOMINAL PAIN, NAUSEA, VOMITING, AND/OR ANOREXIA CAN BE SYMPTOMS OF PANCREATITIS THAT REQUIRE PROMPT MEDICAL EVALUATION. IF PANCREATITIS IS DIAGNOSED, VALPROATE SHOULD ORDINARILY BE DISCONTINUED. ALTERNATIVE TREATMENT FOR THE UNDERLYING MEDICAL CONDITION SHOULD BE INITIATED AS CLINICALLY INDICATED. (See WARNINGS and PRECAUTIONS .)

DESCRIPTION

Divalproex sodium is a stable co-ordination compound comprised of sodium valproate and valproic acid in a 1:1 molar relationship and formed during the partial neutralization of valproic acid with 0.5 equivalent of sodium hydroxide. Chemically it is designated as sodium hydrogen bis (2-propylpentanoate). Divalproex sodium has the following structure:

Divalproex sodium occurs as a white powder with a characteristic odor.
DEPAKOTE Sprinkle Capsules are for oral administration. DEPAKOTE Sprinkle Capsules contain specially coated particles of divalproex sodium equivalent to 125 mg of valproic acid in a hard gelatin capsule.

Inactive Ingredients

125 mg DEPAKOTE Sprinkle Capsules: cellulosic polymers, D&C Red No. 28, FD&C Blue No. 1, gelatin, iron oxide, magnesium stearate, silica gel, titanium dioxide, and triethyl citrate.

CLINICAL PHARMACOLOGY

Pharmacodynamics

Divalproex sodium dissociates to the valproate ion in the gastrointestinal tract. The mechanisms by which valproate exerts its therapeutic effects have not been established. It has been suggested that its activity in epilepsy is related to increased brain concentrations of gamma-aminobutyric acid (GABA).

Pharmacokinetics

Distribution

Special Populations

Plasma Levels and Clinical Effect

The relationship between plasma concentration and clinical response is not well documented. One contributing factor is the nonlinear, concentration dependent protein binding of valproate which affects the clearance of the drug. Thus, monitoring of total serum valproate cannot provide a reliable index of the bioactive valproate species.
For example, because the plasma protein binding of valproate is concentration dependent, the free fraction increases from approximately 10% at 40 µg/mL to 18.5% at 130 µg/mL. Higher than expected free fractions occur in the elderly, in hyperlipidemic patients, and in patients with hepatic and renal diseases.

CLINICAL STUDIES

Epilepsy

The efficacy of DEPAKOTE in reducing the incidence of complex partial seizures (CPS) that occur in isolation or in association with other seizure types was established in two controlled trials.
In one, multiclinic, placebo controlled study employing an add-on design (adjunctive therapy), 144 patients who continued to suffer eight or more CPS per 8 weeks during an 8 week period of monotherapy with doses of either carbamazepine or phenytoin sufficient to assure plasma concentrations within the "therapeutic range" were randomized to receive, in addition to their original antiepilepsy drug (AED), either DEPAKOTE or placebo. Randomized patients were to be followed for a total of 16 weeks. The following table presents the findings.

Adjunctive Therapy Study Median Incidence of CPS per 8 Weeks
Add-on Treatment	Number of Patients	Baseline Incidence	Experimental Incidence
* Reduction from baseline statistically significantly greater for DEPAKOTE than placebo at p ≤ 0.05 level.
DEPAKOTE	75	16.0	8.9*
Placebo	69	14.5	11.5

Figure 1 presents the proportion of patients (X axis) whose percentage reduction from baseline in complex partial seizure rates was at least as great as that indicated on the Y axis in the adjunctive therapy study. A positive percent reduction indicates an improvement (i.e., a decrease in seizure frequency), while a negative percent reduction indicates worsening. Thus, in a display of this type, the curve for an effective treatment is shifted to the left of the curve for placebo. This figure shows that the proportion of patients achieving any particular level of improvement was consistently higher for DEPAKOTE than for placebo. For example, 45% of patients treated with DEPAKOTE had a ≥ 50% reduction in complex partial seizure rate compared to 23% of patients treated with placebo.
Figure 1

The second study assessed the capacity of DEPAKOTE to reduce the incidence of CPS when administered as the sole AED. The study compared the incidence of CPS among patients randomized to either a high or low dose treatment arm. Patients qualified for entry into the randomized comparison phase of this study only if 1) they continued to experience 2 or more CPS per 4 weeks during an 8 to 12 week long period of monotherapy with adequate doses of an AED (i.e., phenytoin, carbamazepine, phenobarbital, or primidone) and 2) they made a successful transition over a two week interval to DEPAKOTE. Patients entering the randomized phase were then brought to their assigned target dose, gradually tapered off their concomitant AED and followed for an interval as long as 22 weeks. Less than 50% of the patients randomized, however, completed the study. In patients converted to DEPAKOTE monotherapy, the mean total valproate concentrations during monotherapy were 71 and 123 µg/mL in the low dose and high dose groups, respectively.
The following table presents the findings for all patients randomized who had at least one post-randomization assessment.

Monotherapy Study Median Incidence of CPS per 8 Weeks
Treatment	Number of Patients	Baseline Incidence	Randomized Phase Incidence
* Reduction from baseline statistically significantly greater for high dose than low dose at p ≤ 0.05 level.
High dose DEPAKOTE	131	13.2	10.7*
Low dose DEPAKOTE	134	14.2	13.8

Figure 2 presents the proportion of patients (X axis) whose percentage reduction from baseline in complex partial seizure rates was at least as great as that indicated on the Y axis in the monotherapy study. A positive percent reduction indicates an improvement (i.e., a decrease in seizure frequency), while a negative percent reduction indicates worsening. Thus, in a display of this type, the curve for a more effective treatment is shifted to the left of the curve for a less effective treatment. This figure shows that the proportion of patients achieving any particular level of reduction was consistently higher for high dose DEPAKOTE than for low dose DEPAKOTE. For example, when switching from carbamazepine, phenytoin, phenobarbital or primidone monotherapy to high dose DEPAKOTE monotherapy, 63% of patients experienced no change or a reduction in complex partial seizure rates compared to 54% of patients receiving low dose DEPAKOTE.
Figure 2

INDICATIONS AND USAGE

DEPAKOTE Sprinkle Capsules are indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizure. DEPAKOTE Sprinkle Capsules are also indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.
Simple absence is defined as very brief clouding of the sensorium or loss of consciousness accompanied by certain generalized epileptic discharges without other detectable clinical signs. Complex absence is the term used when other signs are also present.
SEE WARNINGS FOR STATEMENT REGARDING FATAL HEPATIC DYSFUNCTION.

CONTRAINDICATIONS

DIVALPROEX SODIUM SHOULD NOT BE ADMINISTERED TO PATIENTS WITH HEPATIC DISEASE OR SIGNIFICANT HEPATIC DYSFUNCTION.
Divalproex sodium is contraindicated in patients with known hypersensitivity to the drug.
Divalproex sodium is contraindicated in patients with known urea cycle disorders (see WARNINGS ).

WARNINGS

Hepatotoxicity

Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid. These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months. However, physicians should not rely totally on serum biochemistry since these tests may not be abnormal in all instances, but should also consider the results of careful interim medical history and physical examination.
Caution should be observed when administering DEPAKOTE products to patients with a prior history of hepatic disease. Patients on multiple anticonvulsants, children, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease may be at particular risk. Experience has indicated that children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions. When DEPAKOTE is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. Above this age group, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.
The drug should be discontinued immediately in the presence of significant hepatic dysfunction, suspected or apparent. In some cases, hepatic dysfunction has progressed in spite of discontinuation of drug.

Pancreatitis

Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Some of the cases have been described as hemorrhagic with rapid progression from initial symptoms to death. Some cases have occurred shortly after initial use as well as after several years of use. The rate based upon the reported cases exceeds that expected in the general population and there have been cases in which pancreatitis recurred after rechallenge with valproate. In clinical trials, there were 2 cases of pancreatitis without alternative etiology in 2416 patients, representing 1044 patient-years experience. Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis that require prompt medical evaluation. If pancreatitis is diagnosed, valproate should ordinarily be discontinued. Alternative treatment for the underlying medical condition should be initiated as clinically indicated (see BOXED WARNING).

Urea Cycle Disorders (UCD)

Divalproex sodium is contraindicated in patients with known urea cycle disorders.
Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders, a group of uncommon genetic abnormalities, particularly ornithine transcarbamylase deficiency. Prior to the initiation of valproate therapy, evaluation for UCD should be considered in the following patients: 1) those with a history of unexplained encephalopathy or coma, encephalopathy associated with a protein load, pregnancy-related or post-partum encephalopathy, unexplained mental retardation, or history of elevated plasma ammonia or glutamine; 2) those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance; 3) those with a family history of UCD or a family history of unexplained infant deaths (particularly males); 4) those with other signs or symptoms of UCD. Patients who develop symptoms of unexplained hyperammonemic encephalopathy while receiving valproate therapy should receive prompt treatment (including discontinuation of valproate therapy) and be evaluated for underlying urea cycle disorders (see CONTRAINDICATIONS and PRECAUTIONS).

Somnolence in the Elderly

In a double-blind, multicenter trial of valproate in elderly patients with dementia (mean age = 83 years), doses were increased by 125 mg/day to a target dose of 20 mg/kg/day. A significantly higher proportion of valproate patients had somnolence compared to placebo, and although not statistically significant, there was a higher proportion of patients with dehydration. Discontinuations for somnolence were also significantly higher than with placebo. In some patients with somnolence (approximately one-half), there was associated reduced nutritional intake and weight loss. There was a trend for the patients who experienced these events to have a lower baseline albumin concentration, lower valproate clearance, and a higher BUN. In elderly patients, dosage should be increased more slowly and with regular monitoring for fluid and nutritional intake, dehydration, somnolence, and other adverse events. Dose reductions or discontinuation of valproate should be considered in patients with decreased food or fluid intake and in patients with excessive somnolence (see DOSAGE AND ADMINISTRATION).

Thrombocytopenia

The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia [see PRECAUTIONS]) may be dose-related. In a clinical trial of DEPAKOTE (divalproex sodium) as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets ≤ 75 x 10⁹/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of ≥ 110 µg/mL (females) or ≥ 135 µg/mL (males). The therapeutic benefit which may accompany the higher doses should therefore be weighed against the possibility of a greater incidence of adverse effects.

Usage In Pregnancy

VALPROATE CAN PRODUCE TERATOGENIC EFFECTS. DATA SUGGEST THAT THERE IS AN INCREASED INCIDENCE OF CONGENITAL MALFORMATIONS ASSOCIATED WITH THE USE OF VALPROATE BY WOMEN WITH SEIZURE DISORDERS DURING PREGNANCY WHEN COMPARED TO THE INCIDENCE IN WOMEN WITH SEIZURE DISORDERS WHO DO NOT USE ANTIEPILEPTIC DRUGS DURING PREGNANCY, THE INCIDENCE IN WOMEN WITH SEIZURE DISORDERS WHO USE OTHER ANTIEPILEPTIC DRUGS, AND THE BACKGROUND INCIDENCE FOR THE GENERAL POPULATION. THEREFORE, VALPROATE SHOULD BE CONSIDERED FOR WOMEN OF CHILDBEARING POTENTIAL ONLY AFTER THE RISKS HAVE BEEN THOROUGHLY DISCUSSED WTH THE PATIENT AND WEIGHED AGAINST THE POTENTIAL BENEFITS OF TREATMENT.
THERE ARE MULTIPLE REPORTS IN THE CLINICAL LITERATURE THAT INDICATE THE USE OF ANTIEPILEPTIC DRUGS DURING PREGNANCY RESULTS IN AN INCREASED INCIDENCE OF CONGENITAL MALFORMATIONS IN OFFSPRING. ANTIEPILEPTIC DRUGS, INCLUDING VALPROATE, SHOULD BE ADMINISTERED TO WOMEN OF CHILDBEARING POTENTIAL ONLY IF THEY ARE CLEARLY SHOWN TO BE ESSENTIAL IN THE MANAGEMENT OF THEIR MEDICAL CONDITION.
Antiepileptic drugs should not be discontinued abruptly in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus.

Human Data

PRECAUTIONS

Hepatic Dysfunction

See BOXED WARNING, CONTRAINDICATIONS and WARNINGS.

Pancreatitis

See BOXED WARNING and WARNINGS.

Hyperammonemia

Hyperammonemia has been reported in association with valproate therapy and may be present despite normal liver function tests. In patients who develop unexplained lethargy and vomiting or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured. If ammonia is increased, valproate therapy should be discontinued. Appropriate interventions for treatment of hyperammonemia should be initiated, and such patients should undergo investigation for underlying urea cycle disorders (see CONTRAINDICATIONS and WARNINGS – Urea Cycle Disorders and PRECAUTIONS - Hyperammonemia and Encephalopathy Associated with Concomitant Topiramate Use).
Asymptomatic elevations of ammonia are more common and when present, require close monitoring of plasma ammonia levels. If the elevation persists, discontinuation of valproate therapy should be considered.

Hyperammonemia and Encephalopathy Associated with Concomitant Topiramate Use

Concomitant administration of topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either drug alone. Clinical symptoms of hyperammonemic encephalopathy often include acute alterations in level of consciousness and/or cognitive function with lethargy or vomiting.
In most cases, symptoms and signs abated with discontinuation of either drug. This adverse event is not due to a pharmacokinetic interaction. It is not known if topiramate monotherapy is associated with hyperammonemia. Patients with inborn errors of metabolism or reduced hepatic mitochondrial activity may be at an increased risk for hyperammonemia with or without encephalopathy. Although not studied, an interaction of topiramate and valproic acid may exacerbate existing defects or unmask deficiencies in susceptible persons. In patients who develop unexplained lethargy, vomiting, or changes in mental status, hyperammonemic encephalopathy should be considered and an ammonia level should be measured.(see CONTRAINDICATIONSand WARNINGS - Urea Cycle Disorders and PRECAUTIONS - Hyperammonemia).

General

Because of reports of thrombocytopenia (see WARNINGS), inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters, (e.g., low fibrinogen), platelet counts and coagulation tests are recommended before initiating therapy and at periodic intervals. It is recommended that patients receiving DEPAKOTE be monitored for platelet count and coagulation parameters prior to planned surgery. In a clinical trial of DEPAKOTE as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets ≤ 75 x 10⁹/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of ≥ 110 µg/mL (females) or ≥ 135 µg/mL (males). Evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of the dosage or withdrawal of therapy.
Since DEPAKOTE may interact with concurrently administered drugs which are capable of enzyme induction, periodic plasma concentration determinations of valproate and concomitant drugs are recommended during the early course of therapy. (See PRECAUTIONS - Drug Interactions.)
Valproate is partially eliminated in the urine as a keto-metabolite which may lead to a false interpretation of the urine ketone test.
There have been reports of altered thyroid function tests associated with valproate. The clinical significance of these is unknown.
There are in vitro studies that suggest valproate stimulates the replication of the HIV and CMV viruses under certain experimental conditions. The clinical consequence, if any, is not known. Additionally, the relevance of these in vitro findings is uncertain for patients receiving maximally suppressive antiretroviral therapy. Nevertheless, these data should be borne in mind when interpreting the results from regular monitoring of the viral load in HIV infected patients receiving valproate or when following CMV infected patients clinically.

Multi-organ Hypersensitivity Reaction

Multi-organ hypersensitivity reactions have been rarely reported in close temporal association to the initiation of valproate therapy in adult and pediatric patients (median time to detection 21 days: range 1 to 40 days). Although there have been a limited number of reports, many of these cases resulted in hospitalization and at least one death has been reported. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. Other associated manifestations may include lymphadenopathy, hepatitis, liver function test abnormalities, hematological abnormalities (e.g., eosinophilia, thrombocytopenia, neutropenia), pruritis, nephritis, oliguria, hepato-renal syndrome, arthralgia, and asthenia. Because the disorder is variable in its expression, other organ system symptoms and signs, not noted here, may occur. If this reaction is suspected, valproate should be discontinued and an alternative treatment started. Although the existence of cross sensitivity with other drugs that produce this syndrome is unclear, the experience amongst drugs associated with multi-organ hypersensitivity would indicate this to be a possibility.

Information for Patients

Patients and guardians should be warned that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis and, therefore, require further medical evaluation promptly.
Patients should be informed of the signs and symptoms associated with hyperammonemic encephalopathy (see PRECAUTIONS– Hyperammonemia) and be told to inform the prescriber if any of these symptoms occur.
Since DEPAKOTE products may produce CNS depression, especially when combined with another CNS depressant (e.g., alcohol), patients should be advised not to engage in hazardous activities, such as driving an automobile or operating dangerous machinery, until it is known that they do not become drowsy from the drug.
The specially coated particles in DEPAKOTE Sprinkle Capsules have been observed in the stool, but this occurrence has not been associated with clinically significant effects.
Since DEPAKOTE Sprinkle Capsules has been associated with certain types of birth defects, female patients of child-bearing age considering the use of DEPAKOTE Sprinkle Capsules should be advised of the risk and of alternative therapeutic options and to read the Patient Information Leaflet , which appears as the last section of the labeling. This is especially important when the treatment of a spontaneously reversible condition not ordinarily associated with permanent injury or risk of death (e.g., migraine) is considered.
Patients should be instructed that a fever associated with other organ system involvement (rash, lymphadenopathy, etc.) may be drug-related and should be reported to the physician immediately (see PRECAUTIONS - Multi-organ Hypersensitivity Reaction).

Drug Interactions

Drugs for Which a Potentially Important Interaction Has Been Observed

Drugs for Which Either No Interaction or a Likely Clinically Unimportant Interaction Has Been Observed

Drugs for Which a Potentially Important Valproate Interaction Has Been Observed

Drugs for Which Either No Interaction or a Likely Clinically Unimportant Interaction Has Been Observed

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Pregnancy Category D: See WARNINGS .

Nursing Mothers

Valproate is excreted in breast milk. Concentrations in breast milk have been reported to be 1-10% of serum concentrations. It is not known what effect this would have on a nursing infant. Consideration should be given to discontinuing nursing when divalproex sodium is administered to a nursing woman.

Pediatric Use

Experience has indicated that pediatric patients under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those with the aforementioned conditions (see BOXED WARNING). When DEPAKOTE is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks. Above the age of 2 years, experience in epilepsy has indicated that the incidence of fatal hepatotoxicity decreases considerably in progressively older patient groups.
Younger children, especially those receiving enzyme-inducing drugs, will require larger maintenance doses to attain targeted total and unbound valproic acid concentrations.
The variability in free fraction limits the clinical usefulness of monitoring total serum valproic acid concentrations. Interpretation of valproic acid concentrations in children should include consideration of factors that affect hepatic metabolism and protein binding.
The basic toxicology and pathologic manifestations of valproate sodium in neonatal (4-day old) and juvenile (14-day old) rats are similar to those seen in young adult rats. However, additional findings, including renal alterations in juvenile rats and renal alterations and retinal dysplasia in neonatal rats, have been reported. These findings occurred at 240 mg/kg/day, a dosage approximately equivalent to the human maximum recommended daily dose on a mg/m² basis. They were not seen at 90 mg/kg, or 40% of the maximum human daily dose on a mg/m² basis.

Geriatric Use

No patients above the age of 65 years were enrolled in double-blind prospective clinical trials of mania associated with bipolar illness. In a case review study of 583 patients, 72 patients (12%) were greater than 65 years of age. A higher percentage of patients above 65 years of age reported accidental injury, infection, pain, somnolence, and tremor. Discontinuation of valproate was occasionally associated with the latter two events. It is not clear whether these events indicate additional risk or whether they result from preexisting medical illness and concomitant medication use among these patients.
A study of elderly patients with dementia revealed drug related somnolence and discontinuation for somnolence (see WARNINGS – Somnolence in the Elderly). The starting dose should be reduced in these patients, and dosage reductions or discontinuation should be considered in patients with excessive somnolence (see DOSAGE AND ADMINISTRATION).

ADVERSE REACTIONS

Epilepsy

Based on a placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures, DEPAKOTE was generally well tolerated with most adverse events rated as mild to moderate in severity. Intolerance was the primary reason for discontinuation in the DEPAKOTE-treated patients (6%), compared to 1% of placebo-treated patients.
Table 1 uls treatment-emergent adverse events which were reported by ≥ 5% of DEPAKOTE-treated patients and for which the incidence was greater than in the placebo group, in the placebo-controlled trial of adjunctive therapy for treatment of complex partial seizures. Since patients were also treated with other antiepilepsy drugs, it is not possible, in most cases, to determine whether the following adverse events can be ascribed to DEPAKOTE alone, or the combination of DEPAKOTE and other antiepilepsy drugs.

Table 1 Adverse Events Reported by ≥ 5% of Patients Treated with DEPAKOTE During Placebo-Controlled Trial of Adjunctive Therapy for Complex Partial Seizures
Body System/Event	Depakote (%) (n = 77)	Placebo (%) (n = 70)
Body as a Whole
Headache	31	21
Asthenia	27	7
Fever	6	4
Gastrointestinal System
Nausea	48	14
Vomiting	27	7
Abdominal Pain	23	6
Diarrhea	13	6
Anorexia	12	0
Dyspepsia	8	4
Constipation	5	1
Nervous System
Somnolence	27	11
Tremor	25	6
Dizziness	25	13
Diplopia	16	9
Amblyopia/Blurred Vision	12	9
Ataxia	8	1
Nystagmus	8	1
Emotional Lability	6	4
Thinking Abnormal	6	0
Amnesia	5	1
Respiratory System
Flu Syndrome	12	9
Infection	12	6
Bronchitis	5	1
Rhinitis	5	4
Other
Alopecia	6	1
Weight Loss	6	0

Table 2 uls treatment-emergent adverse events which were reported by ≥ 5% of patients in the high dose DEPAKOTE group, and for which the incidence was greater than in the low dose group, in a controlled trial of DEPAKOTE monotherapy treatment of complex partial seizures. Since patients were being titrated off another antiepilepsy drug during the first portion of the trial, it is not possible, in many cases, to determine whether the following adverse events can be ascribed to DEPAKOTE alone, or the combination of DEPAKOTE and other antiepilepsy drugs.

Table 2 Adverse Events Reported by ≥ 5% of Patients in the High Dose Group in the Controlled Trial of DEPAKOTE Monotherapy for Complex Partial Seizures¹
Body System/Event	High Dose (%) (n = 131)	Low Dose (%) (n = 134)
1. Headache was the only adverse event that occurred in ≥ 5% of patients in the high dose group and at an equal or greater incidence in the low dose group.
Body as a Whole
Asthenia	21	10
Digestive System
Nausea	34	26
Diarrhea	23	19
Vomiting	23	15
Abdominal Pain	12	9
Anorexia	11	4
Dyspepsia	11	10
Hemic/Lymphatic System
Thrombocytopenia	24	1
Ecchymosis	5	4
Metabolic/Nutritional
Weight Gain	9	4
Peripheral Edema	8	3
Nervous System
Tremor	57	19
Somnolence	30	18
Dizziness	18	13
Insomnia	15	9
Nervousness	11	7
Amnesia	7	4
Nystagmus	7	1
Depression	5	4
Respiratory System
Infection	20	13
Pharyngitis	8	2
Dyspnea	5	1
Skin and Appendages
Alopecia	24	13
Special Senses
Amblyopia/Blurred Vision	8	4
Tinnitus	7	1

The following additional adverse events were reported by greater than 1% but less than 5% of the 358 patients treated with DEPAKOTE in the controlled trials of complex partial seizures:

Other Patient Populations

Adverse events that have been reported with all dosage forms of valproate from epilepsy trials, spontaneous reports, and other sources are uled below by body system.

Mania

Although DEPAKOTE Sprinkle Capsules have not been evaluated for safety and efficacy in the treatment of manic episodes associated with bipolar disorder, the following adverse events not uled above were reported by 1% or more of patients from two placebo-controlled clinical trials of DEPAKOTE tablets.

Migraine

Although DEPAKOTE Sprinkle Capsules have not been evaluated for safety and efficacy in the treatment of prophylaxis of migraine headaches, the following adverse events not uled above were reported by 1% or more of patients from two placebo-controlled clinical trials of DEPAKOTE tablets.

OVERDOSAGE

Overdosage with valproate may result in somnolence, heart block, and deep coma. Fatalities have been reported; however patients have recovered from valproate levels as high as 2120 µg/mL.
In overdose situations, the fraction of drug not bound to protein is high and hemodialysis or tandem hemodialysis plus hemoperfusion may result in significant removal of drug. The benefit of gastric lavage or emesis will vary with the time since ingestion. General supportive measures should be applied with particular attention to the maintenance of adequate urinary output.
Naloxone has been reported to reverse the CNS depressant effects of valproate overdosage. Because naloxone could theoretically also reverse the antiepileptic effects of valproate, it should be used with caution in patients with epilepsy.

DOSAGE AND ADMINISTRATION

Epilepsy

DEPAKOTE Sprinkle Capsules are administered orally. DEPAKOTE is indicated as monotherapy and adjunctive therapy in complex partial seizures in adults and pediatric patients down to the age of 10 years, and in simple and complex absence seizures. As the DEPAKOTE dosage is titrated upward, concentrations of phenobarbital, carbamazepine, and/or phenytoin may be affected (see PRECAUTIONS - Drug Interactions ).

General Dosing Advice

HOW SUPPLIED

DEPAKOTE Sprinkle Capsules (divalproex sodium coated particles in capsules), 125 mg, are white opaque and blue, and are supplied in bottles of 100 (NDC 0074-6114-13) and Abbo-Pac^® unit dose packages of 100 (NDC 0074-6114-11).

Recommended Storage

Store capsules below 77°F (25°C).

Abbott Laboratories
North Chicago, IL 60064, U.S.A.

Patient Information Leaflet

Important Information for Women Who Could Become Pregnant About the Use of DEPAKOTE®, DEPAKOTE® ER, DEPAKOTE® Sprinkle Capsules, and DEPAKENE®.

Please read this leaflet carefully before you take any of these medications. This leaflet provides a summary of important information about taking these medications to women who could become pregnant. If you have any questions or concerns, or want more information about these medications, contact your doctor or pharmacist.

Information For Women Who Could Become Pregnant

These medications can be obtained only by prescription from your doctor. The decision to use any of these medications is one that you and your doctor should make together, taking into account your individual needs and medical condition.
Before using any of these medications, women who can become pregnant should consider the fact that these medications have been associated with birth defects, in particular, with spina bifida and other defects related to failure of the spinal canal to close normally. Approximately 1 to 2% of children born to women with epilepsy taking DEPAKOTE in the first 12 weeks of pregnancy had these defects (based on data from the Centers for Disease Control, a U.S. agency based in Atlanta). The incidence in the general population is 0.1 to 0.2%.
These medications have also been associated with other birth defects such as defects of the heart, the bones, and other parts of the body. Information suggests that birth defects may be more likely to occur with these medications than some other drugs that treat your medical condition.

Information For Women Who Are Planning to Get Pregnant

Women taking any of these medications who are planning to get pregnant should discuss the treatment options with their doctor.

Information For Women Who Become Pregnant

If you become pregnant while taking any of these medications , you should contact your doctor immediately.

Other Important Information

Your medication should be taken exactly as prescribed by your doctor to get the most benefit from your medication and reduce the risk of side effects.
If you have taken more than the prescribed dose of your medication, contact your hospital emergency room or local poison center immediately.
Your medication was prescribed for your particular condition. Do not use it for another condition or give the drug to others.

Facts About Birth Defects

It is important to know that birth defects may occur even in children of individuals not taking any medications or without any additional risk factors.
This summary provides important information about the use of DEPAKOTE®, DEPAKOTE® ER, DEPAKOTE® Sprinkle Capsules, and DEPAKENE® to women who could become pregnant. If you would like more information about the other potential risks and benefits of these medications, ask your doctor or pharmacist to let you read the professional labeling and then discuss it with them. If you have any questions or concerns about taking these medications, you should discuss them with your doctor.
Abbott Laboratories
NorthChicago, IL 60064, U.S.A.

DEPAKOTE^®
Sprinkle Capsules

DIVALPROEX SODIUM
COATED PARTICLES IN CAPSULES

Patient Information Guide

Administration Guide

DEPAKOTE^® Sprinkle
Capsules (divalproex
sodium coated particles in
capsules) may be
swallowed whole or
capsule spans may be
sprinkled onto any soft
food.

Serving Suggestions

DEPAKOTE^® Sprinkle Capsules (divalproex sodium coated particles in capsules) are designed to provide the medication your physician prescribed in a way that is more convenient for patients and their families. The flavorless sprinkles let the flavor of the food come through so that dosing time is pleasant for all concerned. Soft foods are appropriate for sprinkle dosing. Some examples include: applesauce, pudding, custard, yogurt, ice cream, and oatmeal.
TO
ADMINISTER
WITH FOOD:

1		Hold the capsule so that the end marked "THIS END UP" is straight up. Although the capsule is oversized to help prevent spilling, it must be handled carefully.
2		To open the capsule, hold it carefully, as shown here, and gently twist it apart. You may find it helpful to hold the capsule over the food to which you will be adding the sprinkles. If you spill any of the capsule spans it is important that you start over with a new capsule and a new portion of food.
3		Place all the sprinkles onto a small amount (about a teaspoonful) of soft food such as applesauce or pudding. Several serving suggestions are uled above.
4		Make sure all of the sprinkle/food mixture is swallowed immediately. Chewing should be avoided. Water taken immediately after the sprinkle/food mixture will help make sure all sprinkles are swallowed. Never store any sprinkle/food mixture for future use. Throw away any unused sprinkle/food mixture.

Make sure this medication is taken as your physician prescribed it. If you have any questions, please contact your physician or pharmacist. Keep all your physician appointments as scheduled. Make sure this and all other drugs are kept out of the reach of children.

Note

If you are taking Depakote Sprinkle Capsules, you may notice the specially coated particles of Depakote Sprinkle Capsules in your stool.
Ask your physician or pharmacist about possible side effects with Depakote Sprinkle Capsules.

Abbott Laboratories
North Chicago, IL 60064, U.S.A.

Dantrium® Intravenous(dantrolene sodium for injection)

2011-06-12T00:10:00.001-07:00

DESCRIPTION

Dantrium Intravenous is a sterile, non-pyrogenic, lyophilized formulation of dantrolene sodium for injection. Dantrium Intravenous is supplied in 70 mL vials containing 20 mg dantrolene sodium, 3000 mg mannitol, and sufficient sodium hydroxide to yield a pH of approximately 9.5 when reconstituted with 60 mL sterile water for injection USP (without a bacteriostatic agent).
Dantrium is classified as a direct-acting skeletal muscle relaxant. Chemically, Dantrium is hydrated 1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidinedione sodium salt. The structural formula for the hydrated salt is:
The hydrated salt contains approximately 15% water (3-1/2 moles) and has a molecular weight of 399. The anhydrous salt (dantrolene) has a molecular weight of 336.

CLINICAL PHARMACOLOGY

In isolated nerve-muscle preparation, Dantrium has been shown to produce relaxation by affecting the contractile response of the muscle at a site beyond the myoneural junction. In skeletal muscle, Dantrium dissociates the excitation-contraction coupling, probably by interfering with the release of Ca++ from the sarcoplasmic reticulum. The administration of intravenous Dantrium to human volunteers is associated with loss of grip strength and weakness in the legs, as well as subjective CNS complaints (see also PRECAUTIONS, Information for Patients). Information concerning the passage of Dantrium across the blood-brain barrier is not available.
In the anesthetic-induced malignant hyperthermia syndrome, evidence points to an intrinsic abnormality of skeletal muscle tissue. In affected humans, it has been postulated that “triggering agents” (e.g., general anesthetics and depolarizing neuromuscular blocking agents) produce a change within the cell which results in an elevated myoplasmic calcium. This elevated myoplasmic calcium activates acute cellular catabolic processes that cascade to the malignant hyperthermia crisis.
It is hypothesized that addition of Dantrium to the “triggered” malignant hyperthermic muscle cell reestablishes a normal level of ionized calcium in the myoplasm. Inhibition of calcium release from the sarcoplasmic reticulum by Dantrium reestablishes the myoplasmic calcium equilibrium, increasing the percentage of bound calcium. In this way, physiologic, metabolic, and biochemical changes associated with the malignant hyperthermia crisis may be reversed or attenuated. Experimental results in malignant hyperthermia susceptible swine show that prophylactic administration of intravenous or oral dantrolene prevents or attenuates the development of vital sign and blood gas changes characteristic of malignant hyperthermia in a dose related manner. The efficacy of intravenous dantrolene in the treatment of human and porcine malignant hyperthermia crisis, when considered along with prophylactic experiments in malignant hyperthermia susceptible swine, lends support to prophylactic use of oral or intravenous dantrolene in malignant hyperthermia susceptible humans. When prophylactic intravenous dantrolene is administered as directed, whole blood concentrations remain at a near steady state level for 3 or more hours after the infusion is completed. Clinical experience has shown that early vital sign and/or blood gas changes characteristic of malignant hyperthermia may appear during or after anesthesia and surgery despite the prophylactic use of dantrolene and adherence to currently accepted patient management practices. These signs are compatible with attenuated malignant hyperthermia and respond to the administration of additional i.v. dantrolene (see DOSAGE AND ADMINISTRATION). The administration of the recommended prophylactic dose of intravenous dantrolene to healthy volunteers was not associated with clinically significant cardiorespiratory changes.
Specific metabolic pathways for the degradation and elimination of Dantrium in humans have been established. Dantrolene is found in measurable amounts in blood and urine. Its major metabolites in body fluids are 5-hydroxy dantrolene and an acetylamino metabolite of dantrolene. Another metabolite with an unknown structure appears related to the latter. Dantrium may also undergo hydrolysis and subsequent oxidation forming nitrophenylfuroic acid.
The mean biologic half-life of Dantrium after intravenous administration is variable, between 4 to 8 hours under most experimental conditions. Based on assays of whole blood and plasma, slightly greater amounts of dantrolene are associated with red blood cells than with the plasma fraction of blood. Significant amounts of dantrolene are bound to plasma proteins, mostly albumin, and this binding is readily reversible.
Cardiopulmonary depression has not been observed in malignant hyperthermia susceptible swine following the administration of up to 7.5 mg/kg i.v. dantrolene. This is twice the amount needed to maximally diminish twitch response to single supramaximal peripheral nerve stimulation (95% inhibition). A transient, inconsistent, depressant effect on gastrointestinal smooth muscles has been observed at high doses.

INDICATIONS AND USAGE

Dantrium Intravenous is indicated, along with appropriate supportive measures, for the management of the fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia crises in patients of all ages. Dantrium Intravenous should be administered by continuous rapid intravenous push as soon as the malignant hyperthermia reaction is recognized (i.e., tachycardia, tachypnea, central venous desaturation, hypercarbia, metabolic acidosis, skeletal muscle rigidity, increased utilization of anesthesia circuit carbon dioxide absorber, cyanosis and mottling of the skin, and, in many cases, fever).
Dantrium Intravenous is also indicated preoperatively, and sometimes postoperatively, to prevent or attenuate the development of clinical and laboratory signs of malignant hyperthermia in individuals judged to be malignant hyperthermia susceptible.

CONTRAINDICATIONS

None.

WARNINGS

The use of Dantrium Intravenousin the management of malignant hyperthermia crisis is not a substitute for previously known supportive measures. These measures must be individualized, but it will usually be necessary to discontinue the suspect triggering agents, attend to increased oxygen requirements, manage the metabolic acidosis, institute cooling when necessary, monitor urinary output, and monitor for electrolyte imbalance.
Since the effect of disease state and other drugs on Dantrium related skeletal muscle weakness, including possible respiratory depression, cannot be predicted, patients who receive i.v. Dantrium preoperatively should have vital signs monitored.
If patients judged malignant hyperthermia susceptible are administered intravenous or oral Dantrium preoperatively, anesthetic preparation must still follow a standard malignant hyperthermia susceptible regimen, including the avoidance of known triggering agents. Monitoring for early clinical and metabolic signs of malignant hyperthermia is indicated because attenuation of malignant hyperthermia, rather than prevention, is possible. These signs usually call for the administration of additional i.v. dantrolene.

PRECAUTIONS

ADVERSE REACTIONS

There have been occasional reports of death following malignant hyperthermia crisis even when treated with intravenous dantrolene; incidence figures are not available (the pre-dantrolene mortality of malignant hyperthermia crisis was approximately 50%). Most of these deaths can be accounted for by late recognition, delayed treatment, inadequate dosage, lack of supportive therapy, intercurrent disease and/or the development of delayed complications such as renal failure or disseminated intravascular coagulopathy. In some cases there are insufficient data to completely rule out therapeutic failure of dantrolene.
There are rare reports of fatality in malignant hyperthermia crisis, despite initial satisfactory response to i.v. dantrolene, which involve patients who could not be weaned from dantrolene after initial treatment.
The administration of intravenous Dantrium to human volunteers is associated with loss of grip strength and weakness in the legs, as well as drowsiness and dizziness.
The following adverse reactions are in approximate order of severity:

There are rare reports of pulmonary edema developing during the treatment of malignant hyperthermia crisis in which the diluent volume and mannitol needed to deliver i.v. dantrolene possibly contributed.
There have been reports of thrombophlebitis following administration of intravenous dantrolene; actual incidence figures are not available.
There have been rare reports of urticaria and erythema possibly associated with the administration of i.v. Dantrium. There has been one case of anaphylaxis.

None of the serious reactions occasionally reported with long-term oral Dantrium use, such as hepatitis, seizures, and pleural effusion with pericarditis, have been reasonably associated with short-term Dantrium Intravenous therapy.
The following events have been reported in patients receiving oral dantrolene: aplastic anemia, leukopenia, lymphocytic lymphoma, and heart failure. (See package insert for Dantrium (dantrolene sodium) Capsules for a complete uling of adverse reactions.)
The published literature has included some reports of Dantrium use in patients with Neuroleptic Malignant Syndrome (NMS). Dantrium Intravenous is not indicated for the treatment of NMS and patients may expire despite treatment with Dantrium Intravenous.

OVERDOSAGE

Because Dantrium Intravenous must be administered at a low concentration in a large volume of fluid, acute toxicity of Dantrium could not be assessed in animals. In 14-day (subacute) studies, the intravenous formulation of Dantrium was relatively non-toxic to rats at doses of 10 mg/kg/day and 20 mg/kg/day. While 10 mg/kg/day in dogs for 14 days evoked little toxicity, 20 mg/kg/day for 14 days caused hepatic changes of questionable biologic significance.
Symptoms which may occur in case of overdose include, but are not limited to, muscular weakness and alterations in the state of consciousness (e.g., lethargy, coma), vomiting, diarrhea, and crystalluria.
For acute overdosage, general supportive measures should be employed.
Intravenous fluids should be administered in fairly large quantities to avert the possibility of crystalluria. An adequate airway should be maintained and artificial resuscitation equipment should be at hand. Electrocardiographic monitoring should be instituted, and the patient carefully observed. The value of dialysis in Dantrium overdose is not known.

DOSAGE AND ADMINISTRATION

As soon as the malignant hyperthermia reaction is recognized, all anesthetic agents should be discontinued; the administration of 100% oxygen is recommended. Dantrium Intravenous should be administered by continuous rapid intravenous push beginning at a minimum dose of 1 mg/kg, and continuing until symptoms subside or the maximum cumulative dose of 10 mg/kg has been reached.
If the physiologic and metabolic abnormalities reappear, the regimen may be repeated. It is important to note that administration of Dantrium Intravenous should be continuous until symptoms subside. The effective dose to reverse the crisis is directly dependent upon the individual's degree of susceptibility to malignant hyperthermia, the amount and time of exposure to the triggering agent, and the time elapsed between onset of the crisis and initiation of treatment.

PREPARATION

Each vial of Dantrium Intravenous should be reconstituted by adding 60 mL of sterile water for injection USP (without a bacteriostatic agent), and the vial shaken until the solution is clear. 5% Dextrose Injection USP, 0.9% Sodium Chloride Injection USP, and other acidic solutions are not compatible with Dantrium Intravenous and should not be used. The spans of the vial must be protected from direct light and used within 6 hours after reconstitution. Store reconstituted solutions at controlled room temperature (59°F to 86°F or 15°C to 30°C).
Reconstituted Dantrium Intravenous should not be transferred to large glass bottles for prophylactic infusion due to precipitate formation observed with the use of some glass bottles as reservoirs.
For prophylactic infusion, the required number of individual vials of Dantrium Intravenous should be reconstituted as outlined above. The spans of individual vials are then transferred to a larger volume sterile intravenous plastic bag. Stability data on file at Procter & Gamble Pharmaceuticals indicate commercially available sterile plastic bags are acceptable drug delivery devices. However, it is recommended that the prepared infusion be inspected carefully for cloudiness and/or precipitation prior to dispensing and administration. Such solutions should not be used. While stable for 6 hours, it is recommended that the infusion be prepared immediately prior to the anticipated dosage administration time.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

HOW SUPPLIED

Dantrium Intravenous (NDC 0149-0734-02) is available in vials containing a sterile lyophilized mixture of 20 mg dantrolene sodium, 3000 mg mannitol, and sufficient sodium hydroxide to yield a pH of approximately 9.5 when reconstituted with 60 mL sterile water for injection USP (without a bacteriostatic agent).
Store unreconstituted product at controlled room temperature (59°F to 86°F or 15°C to 30°C) and avoid prolonged exposure to light.
Address medical inquiries to Procter & Gamble Pharmaceuticals, Medical Communications Department, PO Box 8006, Mason, Ohio 45040-8006.
To place an order, call Procter & Gamble Pharmaceuticals Customer Service 800-448-4878.
Mfg. by: Ben Venue Laboratories
Bedford, OH 44146
Dist. By: Procter & Gamble Pharmaceuticals, TM Owner,
Cincinnati, Ohio 45202

Urinary Calcium Excretion - Calcium in Urine

2011-06-12T00:08:00.001-07:00

Overview & Description

This test measures the amount of calcium in urine.
Calcium is needed for many cellular functions. It is especially important for bone structure and muscle activity. The amount of calcium in urine can help find and monitor disorders involving calcium regulation.

Who is a candidate for the test?

This test is ordered to help diagnose diseases of the kidneys, parathyroid glands, or bones.

How is the test performed?

This test is performed on a urine sample collected over 24 hours.
In general, this schedule is followed: On the first day, the person should urinate as usual after getting up. This sample is not saved. Then all urine produced for the next 24 hours is collected in a special container. The next morning's urine is added to the day's collection. The sample must be refrigerated until it is delivered to a healthcare provider.

Preparation & Expectations

What is involved in preparation for the test?

A healthcare provider provides specific instructions. Generally, no special preparation is required.

Results and Values

What do the test results mean?

Normal levels of calcium in urine range from 100 to 300 milligrams per day for persons on a normal diet. For those on a low-calcium diet, from 50 to 150 milligrams per day is normal.
Abnormally high levels of calcium in the urine may indicate:

Cushing's syndrome, which is an excess of hormones known as corticosteroids

idiopathic hypercalcemia, which is an elevated calcium level in the blood with no known cause

milk-alkali syndrome, which is an increased blood calcium level caused by ingesting large amounts of calcium and antacids

osteolytic bone disease, which is any disease that destroys bone

osteoporosis, a thinning of the bones that commonly occurs in the elderly

primary hyperparathyroidism, which is excess activity of the parathyroid gland that causes increased blood calcium levels

renal tubular acidosis, a metabolic defect of the kidneys

sarcoidosis, a disease, thought to be caused by an abnormal immune system, that causes problems in multiple areas of the body but especially the lungs

vitamin D intoxication

Abnormally low levels of calcium may indicate:

hypoparathyroidism, or low activity of the parathyroid gland

malabsorption disorders

renal osteodystrophy or thinning of bones caused by kidney failure

vitamin D deficiency

Attribution

Author:David T. Moran, MD
Date Written:
Editor:Evans, Gwen, BA
Edit Date:03/18/00
Reviewer:Adam Brochert, MD
Date Reviewed:09/19/01

Transplantation of the Lungs - Lung Transplant

2011-06-09T09:33:00.005-07:00

Overview & Description

In lung transplantation, a healthy donor lung is removed from a person who is brain dead and implanted into a person with lung disease who needs a healthy lung. Sometimes one lung is transplanted and sometimes a person is in need of a double lung transplant.

Who is a candidate for the procedure?

Lung transplantation is only offered to persons who have severe failure of their lungs. These are people who doctors feel will not live longer than 1 to 2 years unless they receive a replacement lung. The main reasons for having a lung transplant include:

emphysema, a chronic lung disease

pulmonary fibrosis, a respiratory disease caused by inhaling asbestos fibers

cystic fibrosis, an inherited disease that affects the respiratory and digestive systems

alpha-1-antitrypsin deficiency, a deficiency of a protein produced in the liver that is associated with emphysema and liver disease

pulmonary hypertension, a condition in which pressure in the blood vessels of the lungs increases. This increased pressure causes damage to the blood vessels and heart.

decreased lung function that interferes with normal activities

A person is evaluated by a team of healthcare professionals to see if he or she is a good candidate for a lung transplant. This team includes surgeons, lung specialists known as pulmonologists, social workers, nurses, and transplant coordinators. A few conditions would disqualify a person from receiving a lung transplant. These include:

cancer within the past five years

certain infections, such as tuberculosis or osteomyelitis, a bone infection

severe lung, liver, or kidney problems that would make the operation too risky

A candidate for a lung transplant needs to know that he or she will need to take medications to keep the body from "rejecting" the transplant. That is, the body's immune system would normally attack the new lung because it is something foreign. Immunosuppressants are medications that keep the immune system from attacking the new lung. These medications need to be taken for as long as the new lung functions. The person will also need lifelong follow-up with doctors.
If a person is found to be a good candidate for the transplant, the person's name is placed on a waiting list. It can sometimes take years for a recipient to receive a lung from a donor.

How is the procedure performed?

Usually many organs (heart, lungs, kidneys, pancreas, and liver) are being removed from the brain dead donor. There may be two or three teams who operate on the donor at the same time. After the organs are removed, they are packed for transport to the recipient. The donor's chest and abdomen are sewn up and normal preparations for a funeral take place.
Usually, both lungs are taken out together. If a double lung transplant is to be done, the double lung will be transplanted together. If two single lung transplants are needed, that is, for two separate recipients, the lungs can be separated after they are removed from the donor.
The lungs can only be preserved safely for about 5 to 6 hours. The transplant surgery needs to take place within this timeframe.
The recipient is given general anesthesia. This means that the person is put to sleep with medications and feels no pain. The person is put on a ventilator, or artificial breathing machine, during the surgery. The person is then put on a heart-lung bypass machine. This involves special tubes to move blood around the heart and lungs. The blood is sent into a special machine to keep the blood circulating and full of oxygen. The operation consists of three major parts:

The diseased lung is cut away from its main blood vessel attachments to the heart and to the large airway, known as a bronchus.

The new healthy lung is put in place. The blood vessels and bronchus are connected to the new lung.

Blood flow and airflow are restored to the new lung. The surgeon checks carefully to see if there is any bleeding and if the lung is filling normally with air.

If the new lung is working properly, the incision is closed. The recipient is then taken to the intensive care unit for recovery.
A double lung transplant is done much like two single lung transplants. The surgeon starts with the more diseased lung, removes it, implants the new one, and then moves on to the less diseased side.

Preparation & Expectations

What happens right after the procedure?

The transplant recipient will usually be in the hospital for 7 to 10 days. The person may be on a ventilator overnight to help with breathing. If the person is stable and the donor lung is functioning normally, the breathing machine may be removed at the end of the surgery. The recipient is usually well enough to move out of the intensive care unit after 2 to 3 days.
Immunosuppressant medications are given right before or during the surgery. Blood tests will be done in the first few weeks after transplantation to be sure that the correct dosage of the medications are being given. The recipient will continue to take these medications for the rest of his or her life.
Before leaving the hospital, the person will be given instructions including

how to care for the transplant

how to take the medications

what side effects to expect

how to take care of the surgical scar

early signs and symptoms of rejection

physical activity and rehabilitation

breathing exercises to prevent pneumonia

Home Care and Complications

What happens later at home?

At home, the recipient can expect a slow but steady recovery. Walking is encouraged to help prevent pneumonia and other lung complications. Walking also helps the person to regain strength. Heavy lifting and straining should be avoided for several weeks. Driving is permitted once the incision heals.

What are the potential complications after the procedure?

There are several complications that can affect a recipient of a lung transplant. Some of these can occur right after the surgery and others can occur at any time for the rest of the person's life. Complications include:

infection. A person who takes immunosuppressant medications is more vulnerable to infection. Some infections are minor but some can be life threatening. This is especially true for infections that affect the lungs directly.

major bleeding. This is rare, but in some cases, there is a lot of scarring on the lung and other nearby tissue. These areas may bleed. Sometimes a second operation is needed to remove any blood clots and control the bleeding.

rejection. The body's normal response to a transplanted organ is to reject it. Even though they take medications to prevent rejection, most recipients will have one or more episodes of rejection. These are treated by increasing the dose of the medication or switching to a different medication.

cancer. This is another long-term problem with immunosuppressant medications. The most common cancers that develop are skin cancer and lymphoma, a cancer of the white blood cells.

Attribution

Author:Robert Merion, MD
Date Written:
Editor:Smith, Mary Ellen, BS
Edit Date:06/01/00
Reviewer:Gail Hendrickson, RN, BS
Date Reviewed:09/04/01

Thromboembolic State - Thromboembolism

2011-06-09T09:33:00.003-07:00

Overview, Causes, & Risk Factors

A thromboembolism is a blood clot that forms and then breaks off and travels through the bloodstream to another part of the body.

What is going on in the body?

When a person is cut or injured, the blood clots, or clumps together. This helps to stop the bleeding. Blood may sometimes clot when it is not supposed to, however. For example, a blood clot may form inside a blood vessel or the heart.
A thromboembolism occurs when a blood clot breaks off from where it has formed and travels through the bloodstream. Eventually, the blood clot will get trapped inside a blood vessel that is too small to let it pass. Blood is then unable to flow through this vessel. The lack of blood flow can damage the body parts that normally receive blood from this vessel.

What are the causes and risks of the disease?

The blood clots that break off and form a thromboembolism can be caused by a number of disorders, including:

damage to the blood vessels or heart, which can occur from injury, surgery, infections, heart attacks, and other causes

poor blood circulation, which can occur from severe congestive heart failure, severe varicose veins, and certain irregular heartbeats, called arrhythmias

lack of activity, which can occur during any prolonged illness, surgery, travel, or injury

"thick" blood that has a tendency to form clots. This condition may occur due to cancer, certain medications, pregnancy, and some inherited conditions.

Symptoms & Signs

What are the signs and symptoms of the disease?

The symptoms of a thromboembolism depend on the organ or blood vessel that has lost blood supply. Blood clots in an arm or leg may cause pain, swelling, and increased temperature in the affected area.
A clot that travels to the lung is called a pulmonary embolus. This condition can cause:

chest pain

shortness of breath

rapid heartbeat, known as tachycardia

fainting

death

If a blood clot is formed in the heart, it can travel to almost any organ in the body. This could cause a stroke, which is a type of damage to the brain from lack of blood circulation. In other cases, damage may be done to an arm or leg, or a heart attack or kidney damage may occur. Other areas of the body can also be affected.

Diagnosis & Tests

How is the disease diagnosed?

A thromboembolism is diagnosed based on a person's symptoms. Different imaging tests are done depending on where the clot is thought to be. An ultrasound test, called echocardiography, can often confirm a blood clot in the heart.
If the person is having any trouble breathing or chest pain, a pulmonary embolus, is often suspected. In this case, the provider may order:

a chest x-ray to see if areas of the lung have collapsed

a pulmonary ventilation scan to see how gases are being transferred across the lungs

a pulmonary perfusion scan to check the blood supply to the lungs

If a stroke is suspected, the provider may order:

cerebral angiography, which shows the blood supply to the brain

a cranial CT scan

a cranial MRI

Once the diagnosis is confirmed, other tests are often done to figure out what caused the initial blood clot. Blood tests called the prothrombin time (PT) and partial thromboplastin time (PTT) are commonly done to check the blood's ability to clot.

Prevention & Expectations

What can be done to prevent the disease?

Regular movement of the arms and legs, blood thinners, or special stockings are often used to help prevent blood clots in someone who is bedridden. A person with inherited causes of "thick" blood or arrhythmias is often given blood-thinning medications.

What are the long-term effects of the disease?

A thromboembolism can cause permanent organ damage and even death. Blood clots in the leg may cause long-term swelling and pain in the leg even after the clot goes away. Permanent brain damage from a stroke can leave people unable to walk, talk, or take care of themselves.

What are the risks to others?

A thromboembolism is not contagious and poses no risks to others.

Treatment & Monitoring

What are the treatments for the disease?

Once the diagnosis of thromboembolism is made, medications are usually given to help treat the disorder. These may include "clot busting" medications known as thrombolytics. Blood-thinners, such as heparin or coumadin, may also be given to help reduce the chance of new blood clots forming.
In some people, a special filter device is placed inside the main vein below the heart. This can help keep blood clots in the legs from traveling to the lungs and causing death.
In some cases, surgery is needed to manually remove a blood clot. Other care may be needed for damage to different parts of the body. For example, those with a stroke may need someone to feed them or physical therapy for weakness.

What are the side effects of the treatments?

The most worrisome side effect of clot-busting or blood-thinning medications is serious bleeding. Sometimes this can cause bleeding into the brain. The filter procedure and surgery carry a risk of bleeding and infection.

What happens after treatment for the disease?

Further treatment may be needed for damage to different areas of the body in some cases. The cause of the thromboembolism may also need further treatment.

How is the disease monitored?

An individual on blood-thinning medications will be tested periodically with clotting tests. Any new or worsening symptoms should be reported to the healthcare provider.

Attribution

Author:Bill Harrison, MD
Date Written:
Editor:Smith, Mary Ellen, BS
Edit Date:09/16/00
Reviewer:Adam Brochert, MD
Date Reviewed:07/01/01

Sources

Harrison's Principles of Internal Medicine, 1998, Fauci et al.

Testicular Self-Examination

2011-06-09T09:33:00.001-07:00

Overview & Description

The testicular self-exam is a way to screen for testicular cancer early when it is easiest to cure. During this test, a man examines each of his testicles for abnormal lumps. It should be done regularly because testicular cancer has few obvious symptoms.

Who is a candidate for the test?

All men who have already undergone puberty should perform a testicular self-examination every month. A male whose testes didn't descend into the scrotum by age 3 has a greater risk of testicular cancer.

How is the test performed?

A testicular self-examination (TSE) is done at home. To do a TSE, a man should raise his right leg and rest the foot on a chair. By gently moving the right testicle between the thumb and fingers of one hand he should feel for any lumps on its surface. He should then switch to his left foot on the chair and repeat these actions on the left testicle.
A man should report any abnormalities, including lumps or an enlarged testicle, to his healthcare provider right away.

Preparation & Expectations

What is involved in preparation for the test?

A TSE works best after a warm shower, which loosens up the muscles of the scrotum. That allows easier manipulation of the testicles.

Results and Values

What do the test results mean?

Normally, a testicle feels firm and consistent, and its surface is smooth. One testicle may be slightly larger and hang lower than the other.
An unusually enlarged testicle or a small, hard lump on the surface of a testicle may be a sign of testicular cancer. A healthcare provider should be consulted right away.

Attribution

Author:David T. Moran, MD
Date Written:
Editor:Keefe, Sandy, RN, MSN
Edit Date:05/14/00
Reviewer:Gail Hendrickson, RN, BS
Date Reviewed:08/20/01

Teenage Depression - Depression in Adolescents

2011-06-09T09:32:00.003-07:00

Overview, Causes, & Risk Factors

Depression is a medical condition that leads to intense feelings of sadness or despair. These feelings don't go away on their own. They are not necessarily related to a particular life event.

What is going on in the body?

Depression is a disorder of the brain. Researchers believe that chemicals called neurotransmitters are involved in depression. Nerve impulses cause the release of neurotransmitters from one nerve cell to the next. This release allows cells to communicate with one another. Too little or too much of these important neurotransmitters may be released. This can cause or contribute to depression. These neurotransmitters include serotonin, norepinephrine, and dopamine.

What are the causes and risks of the condition?

There are many theories about what causes depression. Depression may be caused by any of these things:

certain illnesses

certain medicines, including antibiotics and medicines used to treat acne

changes in brain chemicals

heredity

hormonal changes

lack of sunlight

major stresses

negative thinking patterns

Common risk factors for depression in adolescents include:

abuse or neglect

alcohol abuse

breakup of a romantic relationship

chronic illness, such as diabetes

cigarette smoking

divorce of parents

drug abuse and addiction

family history of depression

learning disabilities

low self-esteem

major trauma, such as a natural disaster

other psychiatric disorders, such as attention deficit disorder or adolescent conduct disorder

Adolescent girls are twice as likely to develop depression as adolescent boys.

Symptoms & Signs

What are the signs and symptoms of the condition?

Some symptoms are common in people of all ages with depression. These symptoms include:

appetite problems

decreased energy

difficulty paying attention or making decisions

feeling very sensitive emotionally

feelings of irritability

feelings of sadness, despair, and emptiness

inability to feel pleasure

low self-esteem

loss of motivation and withdrawal from others

pessimism, negativity

sleeping problems

thoughts about suicide and death

Teens with depression may have additional symptoms, including:

alcohol abuse

difficulty with friendships or social outings

drug abuse and addiction

fear of death

frequent vague physical ailments, such as headache

irritability or hostility

poor school performance, tardiness, or absences

problems with authorities

recklessness

sensitivity to failure or rejection

Diagnosis & Tests

How is the condition diagnosed?

Screening tests for depression in teens include:

the Beck Depression Inventory (BDI) 19

the Center for Epidemiologic Studies Depression (CES-D) Scale

the Children's Depression Inventory (CDI) 18

A teen who screens positively on one of these tests should have a comprehensive evaluation for depression. The evaluation may include a medical history, physical examination, and laboratory tests.

Prevention & Expectations

What can be done to prevent the condition?

Depression may not be preventable. However, these steps may be helpful in preventing it:

avoiding alcohol and illegal drugs

avoiding cigarette smoking

getting prompt treatment for other psychiatric disorders

seeking effective treatment for chronic diseases

talking with a counselor after experiencing a major trauma

Depression can lead to suicide. It is important to recognize and treat the condition early. Teens should be encouraged to talk to someone if they are concerned about depression. There are many people to whom they can talk, including:

a clergy member

a family doctor

their own parents, a friend's parent, or a trusted family member

a professional at a mental health center

a psychologist

a school counselor

What are the long-term effects of the condition?

Most adolescents recover well from a single episode of depression. However, episodes are likely to recur. Adolescents with depression are at risk for further episodes of depression later in life. They are also at risk for adult personality disorders.
There is a strong connection between depression and suicide in adolescents. Suicide is the third leading cause of death for people between the ages of 15 and 24.

What are the risks to others?

Depression is not contagious and poses no risk to others.

Treatment & Monitoring

What are the treatments for the condition?

The two most common ways of treating depression in adolescents are with antidepressant medicines and psychotherapy. Often a combination is used. Occasionally, a teen must be hospitalized for intense treatment.
Antidepressant medicines are effective in:

increasing the teen's ability to function in daily life

lowering the risk of suicide

making the teen feel better

Antidepressant medicines known as selective serotonin reuptake inhibitors (SSRIs) can be used in teens. Some common SSRIs include fluoxetine and paroxetine.
Psychotherapy can help adolescents:

cope better with having depression

feel less alone

improve relations with family, friends, and coworkers

learn about depression and how it affects them

learn to recognize and avoid situations that can bring on a depressive episode

learn to view the world and others more positively and more realistically

positively address problems that they may be facing

stop episodes of depression early by recognizing warning signs and symptoms

Treatment of depression in a teen should involve the family as well as the individual.

What are the side effects of the treatments?

Antidepressants may cause mild and usually temporary side effects in some people. The most common side effects are:

agitation

constipation

dizziness

drowsiness

dry mouth

nausea

What happens after treatment for the condition?

An episode of depression in a teen usually responds to treatment with medicine and psychotherapy. The teen can help prevent relapses by living a healthy lifestyle. Some important parts of the healthy lifestyle include:

avoiding alcohol, illegal drugs, and smoking

doing regular exercise

eating a balanced diet, following the food guide pyramid

finding a support system for dealing with depression

finding ways to manage stress

getting enough rest

How is the condition monitored?

Once a teen has an episode of depression, he or she is at higher risk for further episodes. Any new or worsening symptoms should be reported to the healthcare provider. The provider may recommend regular visits to monitor symptoms. The provider may also order blood tests to monitor the levels of medicines.

Attribution

Author:Gail Hendrickson, RN, BS
Date Written:
Editor:Crist, Gayle P., MS, BA
Edit Date:05/31/01
Reviewer:Eileen McLaughlin, RN, BSN
Date Reviewed:09/24/01

Sources

Professional Guide to Diseases, Sixth Edition. Springhouse: Springhouse Corporation, 1998.
"Depression Treatment Guide" www.anxiety.org.za/deprtguide.htm
"Adolescent Depression" www.healthtouch.com/level1/leaflets.htm
"Depression in Teenagers" www.psychologyinfo.com/depression/teens.htm
"Clinical Depression and Children/Adolescents" www.intelihealth.com/specials/depression/htmDeprChildren.htm

Online

Medifocus Guidebook on Peripheral Neuropathy

Doctor Says Surgery May Relieve Pain Of Neuropathy

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How To Use Nitrogesic

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Cancer, brain

Doctor Says Surgery May Relieve Pain Of Neuropathy

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Medifocus Guidebook on Peripheral Neuropathy

Retinal - Vitamin A

Overview & Description

Information

Functions and Sources

What food source is the nutrient found in?

How does the nutrient affect the body?

Attribution

Sources

Relapsing Urinary Tract Infection - Recurring Urinary Tract Infection

Overview, Causes, & Risk Factors

What is going on in the body?

What are the causes and risks of the infection?

Symptoms & Signs

What are the signs and symptoms of the infection?

Diagnosis & Tests

How is the infection diagnosed?

Prevention & Expectations

What can be done to prevent the infection?

What are the long-term effects of the infection?

What are the risks to others?

Treatment & Monitoring

What are the treatments for the infection?

What are the side effects of the treatments?

What happens after treatment for the infection?

How is the infection monitored?

Attribution

Sources

Recommended Dietary Allowances (RDA)

Recommended Dietary Allowances (RDA)

Information

Radial Nerve Damage - Radial Nerve Injury

Overview, Causes, & Risk Factors

What are the causes and risks of the injury?

Symptoms & Signs

What are the signs and symptoms of the injury?

Diagnosis & Tests

How is the injury recognized?

Prevention & Expectations

What can be done to prevent the injury?

Treatment & Monitoring

What are the treatments for the injury?

What are the side effects of the treatments?

What happens after treatment for the injury?

Attribution

Sources

RA - Rheumatoid Arthritis

Overview, Causes, & Risk Factors

What is going on in the body?

What are the causes and risks of the disease?

Symptoms & Signs

What are the signs and symptoms of the disease?

Diagnosis & Tests

How is the disease diagnosed?

Prevention & Expectations

What can be done to prevent the disease?

What are the long-term effects of the disease?

What are the risks to others?

Treatment & Monitoring

Manufactured by
Schering Canada, Inc.
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Key Pharmaceuticals, Inc.
Kenilworth, NJ 07033 USA
27051812
81-483544
Copyright © 1987, 1992,
Key Pharmaceuticals, Inc.,
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USA. All rights reserved.

GEMZAR^®
(GEMCITABINE HCl)
FOR INJECTION

DEXTROAMPHETAMINE SACCHARATE,
AMPHETAMINE ASPARTATE MONOHYDRATE,
DEXTROAMPHETAMINE SULFATE AND
AMPHETAMINE SULFATE TABLETS
CII
5 mg, 10 mg, 20 mg and 30 mg
(Mixed Salts of a Single-Entity Amphetamine Product)

Rx only