Wednesday, June 15, 2011

Doctor Says Surgery May Relieve Pain Of Neuropathy

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 .

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


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


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.

Sunday, June 12, 2011

Retinal - Vitamin A

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

    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)

    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
    CompoundunitsAdultAdultChildrenInfantsPregnantLactating+


    Males (25+years)Females (25+years)4-8 years6-12 mos.

    Biotinmcg30*30*12*6*30*35*
    Calcium (Ca)mg1200*1200*800*270*1000*1000*
    Chloride (Cl)mg750750600300750750
    Chromium (Cr)mcg50-20050-20050-20020-6050-20050-200
    Copper (Cu)mg1.5-31.5-31-20.6-0.71.5-31.5-3
    Fluoride (F)mg4*3*1*0.5*3*3*
    Folatemcg400*400*200*80*600*500*
    Iodine(I)mcg15015012050175200
    Iron (Fe)mg10(25-50y) 15

    (51+y) 10
    10103015
    Magnesium (Mg)mg420**320**130**75*350-400**310-360**
    Manganese (Mn)mg2-52-52-30.6-1.02-52-5
    Molybdenum (Mo)mcg75-25075-25050-15020-4075-25075-250
    Niacinmg16**14**8**4*18**17**
    Pantothenicmg5*5*3*1.8*6*7*
    Phosphorus (P)mg700**700**500**275*700**700**
    Potassium(K)mg20002000160070020002000
    Proteing635028146065
    Selenium (Se)mcg705530156575
    Sodium (Na)mg500500400200500500
    Vitamin AmcgRE*10008007003758001300
    Vitamin B1(Thiamine)mg1.2**1.1**0.6**0.3*1.4**1.5**
    Vitamin B2 (Riboflavin)mg1.3**1.1**0.6**0.4*1.4**1.6**
    Vitamin B6 (Pyridoxine)mg1.7**1.5**0.6**0.3*1.9**2.0**
    Vitamin B12 (Cyanocobalamin)mcg2.4**2.4**1.2**0.5*2.6**2.8**
    Vitamin Cmg606045359590
    Vitamin Dmcg(51-70y) 10*

    (71+y) 15*
    (51-70y) 10*

    (71+y) 15*
    (1-8y) 5*5*5*5*
    Vitamin Emg

    alpha TE*
    108741211
    Vitamin Kmcg806530106565
    Zinc (Zn)mg15121051519
    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

    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

    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

    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%

    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

    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
    AgeClearance
    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)
    2992.269.44249
    4575.757.04857
    6555.141.56173
    7940.730.77994
    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/CarboplatinCarboplatin
     Number of randomized patients178178
     Median age, years5958
       Range36 to 7821 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

       Evaluable7.9%2.8%
       Bidimensionally measurable91.6%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 months39.9%39.9%
       >12 months59.0%59.6%
     First–line therapy

       Platinum–taxane combination70.2%71.3%
       Platinum–non–taxane combination28.7%27.5%
       Platinum monotherapy1.1%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.) months8.6 (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.) months18.0 (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 Rate47.2%30.9%p=0.0016Chi Square
       CR14.6%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=10146.3%35.6%p=0.11
       CR9.1%4.0%
       PR+PRNM37.2%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/PaclitaxelPaclitaxel
      Number of patients267262
      Median age, years5352
         Range26 to 8326 to 75
      Metastatic disease97.0%96.9%
      Baseline KPSKarnofsky Performance Status. ≥9070.4%74.4%
      Number of tumor sites


         1–256.6%58.8%
         ≥343.4%41.2%
      Visceral disease73.4%72.9%
      Prior anthracycline96.6%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.), months5.2 (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
      Trial28–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 ArmGemzar/
    Cisplatin
    Cisplatin
    Gemzar/
    Cisplatin
    Cisplatin/
    Etoposide

      Number of patients260262
    6966
         Male182186
    6461
         Female7876
    55
      Median age, years6263
    5860
         Range36 to 8835 to 79
    33 to 7635 to 75
      Stage IIIA7%7%
    N/AN/A
      Stage IIIB26%23%
    48%52%
      Stage IV67%70%
    52%49%
      Baseline KPSKarnofsky Performance Status. 70 to 8041%44%
    45%52%
      Baseline KPS 90 to 10057%55%
    55%49%






      Survival

    p=0.008

    p=0.18
         Median, months9.07.6
    8.77.0
         (95%, C.I.) months8.2, 11.06.6, 8.8
    7.8, 10.16.0, 9.7
      Time to Disease Progression

    p=0.009

    p=0.015
         Median, months5.23.7
    5.04.1
         (95%, C.I.) months4.2, 5.73.0, 4.3
    4.2, 6.42.4, 4.5
      Tumor Response26%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

    Gemzar5–FU
      Number of patients6363
         Male3434
         Female2929
      Median age62 years61 years
         Range37 to 7936 to 77
      Stage IV disease71.4%76.2%
      Baseline KPSKarnofsky Performance Status.≤7069.8%68.3%



      Clinical benefit response22.2%
    (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
         Median5.7 months4.2 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%
         Range0.2 to 18.6 months0.4 to 15.1+No progression at last visit; remains alive. months
         95% C.I. of the median4.7 to 6.9 months3.1 to 5.1 months
      Time to Disease Progression

    p=0.0013
         Median2.1 months0.9 months
         Range0.1+ to 9.4 months0.1 to 12.0+ months
         95% C.I. of the median1.9 to 3.4 months0.9 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
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    Indianapolis, IN 46285, USA
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