Monthly Archives - March 2008

FDA Probes Heart Risk From 2 HIV Drugs

FDA Probes Heart Risk From 2 HIV Drugs

FDA Reviewing Heart Attack Data in HIV Patients Taking Ziagen and Videx

By
Miranda Hitti
WebMD Medical News

Reviewed by
Louise Chang, MD

March 28, 2008 — The FDA is reviewing data on heart attack risk in HIV
patients taking the anti-HIV drugs Ziagen and Videx.
The FDA’s review centers on the Data Collection on Adverse Events of Anti
HIV Drugs (D:A:D) study, which includes more than 33,000 HIV patients in North
America, Europe, and Australia.
The D:A:D study is tracking short-term and long-term adverse events of
treatment with anti-HIV drugs.
According to the FDA, analyses of D:A:D data gathered through Feb. 1, 2007,
show that recent use of Ziagen or Videx was associated with an increased risk
of heart attack. “Recent use” refers to current use of the drugs or
using the drugs within the past six months.
“Patients taking either of these drugs had a greater chance of
developing a heart attack than patients taking other medications,” states
the FDA. “The risk did not appear to increase over time, but remained
stable and appeared to be reversible after [Ziagen] or [Videx] were
stopped.”
Heart attack risk appeared to be greater in patients who had other heart
disease risk factors, including smoking, older age, high cholesterol, high
blood pressure, diabetes, and a history of heart disease.
The FDA considers those analyses to be incomplete. Because the FDA’s review
isn’t finished, the FDA isn’t telling anyone to stop using or prescribing
Ziagen and Videx. At this point, the FDA advises patients and doctors to weigh
the risks and benefits of each HIV drug they use, including Ziagen and
Videx.

Drug Companies Respond

Ziagen is made by GlaxoSmithKline.
In a news release, GlaxoSmithKline states that its analyses show no
increased risk of heart attack associated with Ziagen and that no biological
mechanism linking Ziagen treatment to heart attacks has been identified.
GlaxoSmithKline advises patients not to discontinue treatment on their own,
and to minimize modifiable cardiovascular risk factors such as high blood
pressure, high cholesterol, diabetes, and smoking.
“Although the D:A:D study data suggest a relative risk increase in heart
attack risk for patients who are starting or continuing [Ziagen], that risk
remains low in absolute terms, and therefore [Ziagen] remains an important
treatment option for those patients,” states a GlaxoSmithKline news
release.
Videx is made by Bristol-Myers Squibb.
“We have not seen an increase in cardiovascular events in prior studies
of Videx or in our safety database,” Bristol-Myers Squibb spokeswoman Sonia
Choi tells WebMD.

HIV Cruise Raises $6000 for HIV causes


The HIV Cruise Retreat : A Fun Source of Education and Funds for HIV Projects

CONTACT: Paul Stalbaum at Paul@universal-travel.com
800-735-0401 ext 241

Fort Lauderdale, March 21, 2008- A group of 225 HIV positive men and women went sailing away from the worries of the disease while obtaining key health information and raising funds for HIV non profit projects. In this 10th year, the retreat raised $6,000 for Doctor’s Without Borders. Over $30,000.00 has been raised over the past 10 years.

“It is great to have people who have been challenged for years with fears of death enjoy life in the company of others who are on the same boat as they are”, said Nelson Vergel, AIDS activist and lecturer on the cruise. “I am glad our project leader Paul Stalbaum has been able to make this possible for so many people to spend a week sailing the seas at affordable prices while they get key medical information and bond with others” added Vergel.

“As a doctor who treats hundreds of HIV patients, I must say that spending a week with so many people having fun while being helped with medical information is an ideal scenario”, said Dr Michael Wohlfieler, a leading South Florida HIV physician and featured speaker on the cruise.

Sam, a long term survivor from San Francisco and participant of last year’s cruise said: “We remember all too well when the virus was considered more or less a signal that it was time to get one’s affairs in order. Thankfully those days are behind us. A week like the one I had on this cruise reminds me that life is rich and full and when the good times roll it can be downright amazing”. “I will definitely not miss this year’s cruise!” added Sam.

“This year’s cruise promises to be even better with a very exciting itinerary sailing over Halloween from Ft Lauderdale with stops at Grand Turk (Turks and Caicos), St Maarten, St Thomas and Princess Cays”, said cruise organizer Paul Stalbaum. “We will actually have separate fun activities for gay and straight groups with some intermingling ” added Stalbaum.

For more information please call Paul at 800-735-0401 ext 241 or visit his two web sites: http://www.hivcruise.com/ for the gay group and http://www.positivecruise.com/ for the heterosexual group.

HIV Lipodystrophy: Where are we after 10 years?

From Gay Men’s Health Crisis

HIV Lipodystrophy: Where Are We After Ten Years?
By Nelson Vergel
July-December 2007

Note: The following article expresses the opinions and learned lessons of the writer, not of GMHC, Treatment Issues, or their staff. It is not intended as medical advice and should not be taken as such.

Ten years have passed since the first report of lipodystrophy at an HIV conference. The excitement and hope for a longer life that accompanied the arrival of Highly Active Anti-Retroviral Therapy (HAART) has been tempered by accounts of humps, bellies, and facial wasting. A decade on, many unanswered questions and misconceptions about HIV associated lipodystrophy persist with only a limited number of treatment options available. Frustrated and tired of waiting for answers from the medical community, many people living with lipodystrophy have turned to the internet for advice, treatment and support in hopes of reversing some of the devastating effects of this stigmatizing syndrome.
Lipodystrophy is a condition of abnormal fat redistribution that can lead to either lipohypertrophy (fat accumulation in specific areas of the body such as the neck, belly, upper torso, and breasts) or lipoatrophy (fat loss in the face, buttocks, arms and legs). An online survey of 695 people (predominantly white men, over the age of 40, living with HIV for over 10 years and with exposure to HAART for at least that long) found that 20% had considered suicide because of body shape changes associated with lipodystrophy. Almost 90% of respondents believed that their HIV medications caused lipodystrophy, and 20% had stopped taking their HIV medications altogether due to this concern. Further, over 60% of respondents reported being rejected by potential sexual partners because of the syndrome. A similar number of respondents indicated that they had stopped looking into the mirror because of crippling body dissatisfaction. Nearly all of the respondents attempted to curb the effects of lipodystrophy with diet and exercise or by using costly facial reconstruction procedures, supplements and hormones — treatments not typically covered by insurance companies or drug assistance programs.

Lipoatrophy and HIV Medications

In 1999, the HIV drug Zerit was correlated with the development of lipoatrophy related fat loss under the skin.1 Since then, several studies have concluded that Zerit can affect the way our mitochondria (energy factories in our cells) work and multiply. Later studies also linked lipoatrophy to AZT, although at a lower rate than Zerit. Nucleoside reverse transcriptase inhibitors (NRTIs) like Zerit and AZT, keep HIV from altering the genetic material of healthy T-cells, thereby halting the reproduction of new virus cells. Additionally, NRTIs affect the mitochondria in fat cells under the skin, preventing them from multiplying and causing them to die. Also, those who have taken Zerit and Videx (another NRTI) together report more lipoatrophy than those taking Zerit alone. This combination is not recommended by guideline groups. It appears that Zerit and AZT make fat accumulation worse in the presence of protease inhibitors or non-nucleoside analogs (NNRTIs) like Sustiva, leading researchers to suspect that their negative effect may play a combined role. However, Sustiva taken with Viread (Tenofovir) and Epivir (3TC) seems to cause less lipoatrophy. Due to the high risk of developing lipoatrophy and neuropathy, the US Department of Health and Human Services guidelines committee dropped Zerit from the list of recommended drugs for first line therapy for people new to HAART.

Viread (Tenofovir) and Ziagen (Abacavir), two other NRTIs in the same drug class as Zerit and AZT, do not seem to strongly correlate with the development of lipoatrophy. Some people have even reported a slow reversal of the fat loss after switching from Zerit or AZT to either Ziagen or Viread. However, even after a number of years most patients do not experience re-accumulation of fat in their faces after going off AZT or Zerit. It is also important to note that puzzling new data from a recent study by the AIDS Clinical Trials Group2 showed that 20% of subcutaneous fat loss (loss in body fat closer to the skin’s surface) occurred in a small percentage of patients starting HAART for the first time with a combination of Sustiva, Viread and Epivir. More studies are needed to determine why lipoatrophy still occurs in some patients in the absence of Zerit or AZT.

The sales of Zerit and AZT in the industrialized world have dropped considerably in the past years due to their effects on lipoatrophy. Unfortunately, these two drugs are among the primary HIV medications used in the developing world, so millions of people in poorer countries will continue to suffer with body changes.

Treatment Options for Lipoatrophy

In recent years many men have relied on an off-label injectable anabolic steroid called nandrolone decanoate (old trade name: Deca Durabolin), to “balance out” their bodies and add muscle to their thin extremities and buttocks affected by lipoatrophy. Even though Watson Laboratories ceased production of nandrolone in March of 2007, it is still available through prescription at compounding pharmacies for a low cost.3

Uridine (Nucleomaxx), a supplement made of sugar cane and available through a German supplier,4 may lessen lipoatrophy in patients taking Zerit, however it may also cause abdominal fat and high triglycerides. These side effects, along with high cost and bad taste, make Uridine an unpopular choice. However, for those who must take Zerit, Uridine may be a viable option to prevent or reverse lipoatrophy. Additionally, for those who are no longer taking Zerit, the diabetes drug Rosiglitazone (Avandia) works well for reversing lipoatrophy. There are side effects however, including weight gain and high triglycerides.

Since 2002 there have been a couple of non-permanent reconstruction procedures available to treat facial lipoatrophy. The face wasting reconstruction option, Sculptra (polylactic acid, old name: NewFill) entails an expensive series of multiple sessions, requiring additional touch ups that can be used to treat those moderately affected by lipoatrophy. Radiesse, another FDA approved option, seems to last a little bit longer but is also costly, requiring 3?5 sessions and yearly touch ups. Some patients treated with face wasting fillers experience side effects such as bruising and treatable granulomas (hardened pimple-like nodules). There are patient assistance programs available for both Sculptra and Radiesse.5

There are no FDA approved permanent solutions for facial lipoatrophy, yet many in the US seek tiny injections of silicone (Silikon 1000) from their doctors. Silikon 1000 can be used legally in an off-label manner for facial lipoatrophy. Silikon 1000 micro-injections can reconstruct patients’ faces slowly over five sessions spaced one month apart. There is no patient assistance program for this option and sessions cost anywhere from $600 to $900. Here too, multiple sessions are required. Beware that very few US doctors are well trained in this procedure.
Another permanent product, Polymethylmethacrylate (PMMA), has been used in Brazil for eight years and in Mexico for three with relatively positive results, though more time is needed to determine the long term effects of this procedure. Usually 2?4 sessions are required and no yearly touch ups are needed. Short term, we have seen that PMMA can harden and be lumpy in certain patients, but many people seem pleased with the results. Artefill, a PMMA based product, is FDA approved for cosmetic purposes but not for HIV related lipoatrophy. Artefill is extremely expensive for the amount required to treat lipoatrophy, so some HIV positive people in the US go to Mexico or Brazil for the procedure, where costs can range from $2000 to $6000. PMMA is not removable.

BioAlcamid (poly-alkylamide gel), also permanent, is an injectable filler unavailable in the US (some patients travel to Mexico or Canada for injections). Unfortunately, BioAlcamid forms a “pocket” in the face and buttocks enabling bacteria to penetrate and posing a high risk of infection. As such, extreme caution is warranted before pursuing this option.
It is critical to remember that no long-term data on these experimental facial reconstruction treatments are available, so one must weigh the risks of injecting a foreign substance into one’s body. Sadly, many people find that the emotional, psychological and social toll of living with lipoatrophy is so great as to justify these risks.

Understanding LipohypertrophyUnlike lipoatrophy, researchers have not been able to attribute lipohypertrophy (fat gain in the belly, back of neck and breasts) to any specific medication or drug class. Protease inhibitors were once thought to be the main culprits. However, researchers have recently discovered that fat gain in the belly may relate to inflammatory responses in the immune system when CD4 cells increase in number. This means that those who start HAART with a lower baseline CD4 count may see greater lipodystrophy. Moreover, recent data shows that patients with a CD4 count of over 250, who start a HAART regime with protease inhibitors boosted with Norvir plus Viread and Epivir, do not experience a gain in visceral fat (fat surrounding the internal organs). It is still too early to tell what happens to those on this particular regimen who start with lower CD4 counts. Some studies have shown that those who begin taking protease inhibitors in combination with Zerit, AZT or Zerit plus Videx seem to have more visceral and hump fat gain than those who start on protease inhibitors with other drugs. It may be that the same drugs that are linked to lipoatrophy may also make fat gain worse, especially in patients who start HAART with fewer CD4 cells.

A common misconception promoted by a few pharmaceutical companies and echoed by some doctors is that HIV medications that do not increase cholesterol, and that triglycerides do not cause fat gain. On the contrary, several studies have shown that people taking lipid friendly drugs like Reyataz with Viread also gain fat in the belly after starting HAART.

Dr. David Nolan, a clinician and researcher at Royal Perth Hospital in Western Australia and an expert on fat metabolism and HIV, was asked about why visceral fat does not get “burned off” by Zerit and AZT like subcutaneous fat does. Dr. Nolan hypothesized that fat cells in the organ cavity may not be as susceptible as subcutaneous fat cells to the mitochondrial toxicity caused by Zerit and AZT.

Fat gain may also be linked to insulin resistance. Insulin resistance can cause glucose intolerance, which has been associated with fat gain, increased triglycerides, and the development of diabetes. Insulin is a hormone produced by the pancreas to control blood sugar-glucose. HIV medications may block or slow down the process by which insulin converts glucose to energy. In laboratory studies, Crixivan and higher doses of Norvir and Zerit have been shown to impair the action of insulin in fat and muscle cells. In this scenario the pancreas will tend to produce more and more insulin to compensate for the decrease in function. High insulin levels may be present for years before type 2 diabetes develops. A glucose tolerance test (GTT) may reveal that problem easily but it is hardly used in clinical practices. Additionally, some people may have a genetic predisposition to insulin resistance. A sedentary lifestyle and a diet rich in sugars and animal fats may also compound this problem. In any case, insulin resistance may just be a part of the mystery of lipohypertrophy. There is no agreement among researchers whether or not monitoring insulin levels in HIV-positive people is justifiable or dependable as a tool to assess insulin resistance and fat gain.

The full body dual x-ray absorptiometry (DEXA) scan is the gold standard test in lipodystrophy. It is a highly valuable test that can provide information about body fat, muscle mass and bone density (low bone density has been associated with HIV in several studies.) Both Medicare and private insurance often cover this inexpensive test. While the scan cannot differentiate between fat accumulated in the belly on under the skin in the abdominal area, it can be useful as a baseline to assess body changes and to justify reimbursable therapies for fat, muscle, and bone mass.

Treatment Interventions for Lipohypertrophy

Some people have switched from protease inhibitors to Viramune or Sustiva to combat visceral fat gain, but this has not been shown to make a difference. It is not yet known what happens to belly fat when a patient switches from Zerit or AZT to Viread or Ziagen while taking protease inhibitors or non-nucleoside analogs like Sustiva or Viramune.

The recombinant human growth hormone Serostim is a daily injectable drug approved by the FDA for HIV associated wasting. At approximately $3000 a month, it is an expensive option for treating lipodystrophy. Serostim works well in lowering abdominal fat but has many side effects including joint pain, water retention, carpal tunnel syndrome, and irreversible diabetes. These side effects and the lack of proven long-term health benefits are why the FDA has not approved Serostim for the treatment of HIV related fat accumulation. Tesamorelin-TH9507, made by Theratecnologies, is a daily injectable growth hormone precursor that is in its last stages of FDA approval. Tesamorelin appears to have fewer side effects than Serostim, but may take a longer time to show benefits in patients. Disappointingly, fat gain returns after discontinuation of both Serostim and Tesamorelin.

Leptin, a hormone that produced by fat cells, is another new contender in the search to decrease visceral fat. Researchers have found that leptin levels in the blood are proportional to an individual’s level of body fat. Leptin works in the part of the brain that controls appetite and other basic functions. High levels of leptin generally suppress the appetite and stimulate the burning of fat. Leptin does not appear to have a negative impact on glucose tolerance.

Nowadays, physicians are likely to prescribe testosterone gels, injections, and subcutaneous pellets. A testosterone gel applied to the belly can reduce the waist size in HIV-positive men. This decrease is usually as a result of a reduction in subcutaneous fat, not in visceral fat. In contrast, a small pilot study of Oxandrin (an oral anabolic steroid) has yielded encouraging results in decreasing visceral fat. Increases in the low density lipoprotein (the “bad” cholesterol) and decreases in the high density lipoprotein (the “good” cholesterol) correspond to a small decrease in subcutaneous fat. There are no data yet on a connection with the popular anabolic steroid, nandrolone decanoate, and visceral fat reductions.

Some individuals who have been looking elsewhere for fat burners have fallen prey to advertisements pushing growth hormone supplements or fat burners. These products do little but increase blood pressure and anxiety and are generally considered scams.

Metformin (trade name, Glucophage), is a generic diabetes drug that has been shown to improve glucose tolerance and lower visceral fat. Its effects may be enhanced by exercise. Metformin improves insulin sensitivity, triglycerides and fatty liver but can also cause diarrhea and weight loss. There have also been reports of low blood sugar and dizzy spells associated with this drug.

In addition to the aforementioned treatments many patients explore liposuction. Ultrasound-assisted liposuction can be used to successfully remove fat accumulated in buffalo humps and around the neck.

Some patients complain about the enlargement of salivary glands on each side of the face commonly referred to as the “chipmunk look.” While only a few radiologists know how to use it for this purpose, low dose electron radiation has worked very effectively in treating the enlargement of salivary parotid glands. It is unknown whether the “chipmunk look” is related to lipodystrophy or caused by immune reconstitution.

Another under explored intervention is diet and exercise. A study at Tufts University revealed a trend towards less lipodystrophy in those who had higher consumption of soluble fiber (fruits and vegetables) and who exercised. However more research is needed with the use of diets lower in simple carbohydrates. These diets have been shown to improve insulin resistance and visceral fat in non-HIV studies. One observational cohort showed that people with HIV eat more saturated fats. A small pilot on a combination of cardiovascular and resistance exercise showed decreased triglycerides and visceral fat. However, adherence to exercise remains a challenge to many people, and exercise research in HIV generally remains in its infancy.

Increased Lipids: Low Density Lipoprotein (LDL) and Triglycerides

The most common lipid abnormalities in HIV are high triglycerides and LDL, “bad” cholesterol, and low High Density Lipoprotein (HDL), “good” cholesterol. Before HIV-positive people start HIV medication for the first time, both their high and low density lipoprotein may be lower than normal. However, after HIV drugs are started, low and high density lipoproteins and triglycerides increase in some people. Some studies have shown that LDL increases to “pre-HIV” levels while HDL never returns to normal levels. Increased triglycerides is the most strongly associated lipid change caused by HIV medications such as protease inhibitors, Zerit, AZT, or Sustiva. Among protease inhibitors, Reyataz seems to correlate with the lowest lipid increases.

Many people want to start supplements before they start lipid lowering medications. The only supplements with solid emerging data on lipids are omega-3 fatty acids (fish oils), and niacin (also available as Niaspan). Fish oils can decrease triglycerides but some patients’ stomachs cannot tolerate them. Niacin is better than any lipid lowering drug in increasing the “good” cholesterol (HDL). It can cause flushing of the face and a hot sensation for a half an hour at a time, but most people get used to it. Non-flush versions are available but their effectiveness is unknown.

It is not clear if Raltegravir (Isentress, the first integrase inhibitor) or Maraviroc (Celsentry — a CCR5 entry inhibitor) have any effect on body composition. So far, they appear to be lipid friendly when taken with Viread and Epivir. Fuzeon (an injectable entry inhibitor) also seems to be lipid friendly, but it is usually used with boosted protease inhibitors that can cause increases in lipids. It seems that there may be genetic factors that make some patients more prone to increased low density lipoprotein (bad) cholesterol and triglycerides.

Lipid lowering agents like statins (Lipitor, etc) or fibrates (Tricor, etc.) can work wonders in many, but even with their use, some patients never reach “normal” lipid levels. A combination of niacin, lower sugar and animal fat intake, exercise, fish oil supplements or an increase in fatty cold water fish consumption (salmon) and soluble fiber (fruits, vegetables, oats) are sometimes used to treat lipids. Some individuals have tried combining statins and fibrates, but this combo can lead to an increase in muscle related disorders in some patients.

Conclusion

We have learned a lot during the past 10 years about body changes associated with HIV, but many more questions remain. It is the hope that those new to HAART therapy will not have to suffer the devastating drug side effects that their predecessors have had to contend with in the past 20 years. As patients, it is our responsibility to stay educated and learn from others about emerging options that may make it possible one day to live fully without HIV related body changes and other side effects.

For more information visit: http://www.facialwasting.org/ or to subscribe to the largest internet HIV health discussion group send a blank email to pozhealth-subscribe@yahoogroups.com

Nelson Vergel is director of Program for Wellness Restoration.

A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang JM, Gastaut JA, Touraine JL. AIDS. 1999 Sep 10;13(13):1659-67.
Metabolic Outcomes of ACTG 5142: A Prospective, Randomized, Phase III Trial of NRTI-, PI-, and NNRTI-sparing Regimens for Initial Treatment of HIV-1 Infection. Richard H. Haubrich, S Riddler, G DiRienzo et al.
More information is available at http://www.medibolics.com/.
More information is available at http://www.nucleomaxx.com/.
More information is available at http://www.facialwasting.org/.

IMPORTANT INFORMATION ABOUT NANDROLONE IN THE US

QUESTION FROM SOMEONE IN MY POZHEALTH AT YAHOOGROUPS.COM LIST:

“I interpret this that once the current supply of the components tomake nandrolone are depleted, there will be no more access tonandrolone here in the US. Am I right or just the number ofcompounding pharmacies may continue to dwindle due to DEA pressures?Thanks everyone,Tom A”

MY ANSWER:

Dear Tom

The ingredients to make nandrolone are not depleted. The decision from the manufacturer (Watson) to stop making nandrolone decanoate (an effective injectable medicine to treat unintentional weight loss and to increase muscle mass) was based on economics and political pressure.

Watson stopped making it because:

1- It is a generic CHEAP drug
2- They can sell expensive Oxandrin instead. Oxandrin is approved for unintentional weight loss but costs $1200 a month and can cause liver toxicity in some.
3- Nandrolone’s indication is for anemia and no doctor uses it for that purpose, so they prescribe it legally off label.
4- Congress and the DEA are treating anabolics like the treat crack-cocaine and are closely watching every prescriber’s and manufacturer’s move. No HIV doc has ever got in trouble since many studies have shown nandrolone’s benefit and can justify its medical use. However, inexperienced HIV doctors who have not been around long enough to know its history shy away from prescribing due to the bad publicity and misconceptions around these medicines.

Compounders picked it up and are making it cheap at $13 per 200 mg (1 cc). Watson’s retail price was $48 per 200 mg (1 cc). Most people do ok with 1 cc a week along with daily testosterone gel. Most are able to gain 10 pounds of muscle slowly at this dose with the use of exercise and good nutrition. This amounts to a total cost of $52 a month, compared to $1200 a month for oral Oxandrin, another anabolic prescribed and approved for unintentional weight loss.

Nandrolone is the cheapest, cleanest, most effective medicine out there to increase muscle mass, strength and functional capacity. Like all medicines, it is only advisable to use it with doctor’s supervision so that your hematocrit /hemoglobin, blood pressure, free testosterone/estradiol, and PSA are monitored. It has been studied in several HIV studies and it has been shown effective and low in side effects up to 600 mg a week. It has been studied in women with HIV also.

We are losing this drug in the US because patients who use it and love it are not empowered to fight back, even with Michael’s, Al’s and my help. More and more HIV doctors are getting afraid to prescribe it even after prescribing it without problems for 15 years. And most patients thing it is not available anymore, so they start oral Oxandrin at $1200 a month and experience liver problems.

I am glad someone in this list wrote a wonderful letter to congress, but it will take more from you guys than that. Calling your congress people, sending letters, and talking to your doctors are all a good start.

I will keep pushing. If the day comes when we have no nandrolone, I will opt for foreign travel. I am trying to get some small companies interested in it since there are enough data to go to the FDA with a new drug application (IND) for a HIV unintentional weight loss indication (I did not say “wasting” since most people do not lose 10% of their weight anymore unless they get PCP, excessive diarrhea, or other complications)

One important development:

Applied Pharmacy stopped all production due to DEA pressure. Some compounders are making doctors sign a waiver to say they will not prescribe nandrolone for non medical uses. Some doctors feel this represents extra liability. I am attaching the letter from Medaus so that you guys can see it.

So far, we are happy with these guys in Los Angeles. They ship anywhere after receiving a doctor’s prescription

www.bbpharmacy.com
(562) 866-8363

FOR BACKGROUND INFORMATION ( PRINT AND GIVE IT TO YOUR DOCTOR): http://savehivwastingmeds.blogspot.com/

This is the letter that Mark Mier from this list wrote recently. Please feel free to copy and paste text in it to write your own letter!

March 12, 2008

The Honorable Nancy Pelosi
Speaker of the United State House of Representatives
235 Cannon HOB
Washington, DC 20515

Subject: Representative Henry Waxman’s Hearings on Steroids in Sports and the Impact on Treatments for HIV and other Medical Conditions

Dear Madam Speaker:

The hearings Representative Henry Waxman has been conducting with respect to steroids in sports have had an adverse impact upon treatment for a variety of medical condition for which anabolic steroids and human growth hormones are legitimately and legally used. Among those conditions is HIV, a matter of substantial concern to many in your own district.

The manner in which these hearings have been conducted has created a level of hysteria that has painted all anabolic supplements and medications as unsavory and illegitimate. Certainly illegal use of human growth hormones and steroids in both professional and youth sports is a concern that needs to be addressed. But Representative Waxman’s hearings, as conducted, have highlighted only the negative aspects of such medicine and have not mentioned at all how they are properly and legitimately used and how controls on illegal use should be limited so as not to impact availability for proper usage. I am sure Representative Waxman appreciates the manner in which his name has been prominently highlighted in the press, but members in the HIV community have found him to have little interest in doing anything that will address our concerns in any concrete and demonstrable manner.

Anabolic steroids and recombinant human growth hormone are powerful prescriptive medicines that have been highly effective in treating cancer cachexia, MS, burns and HIV-related wasting and body changes. With respect to HIV, these treatments have been used successfully by thousands of sufferers in combating wasting, a condition which in the past was among the leading causes of death from AIDS. Since use of anabolic steroids and growth hormone to combat wasting began in the late 1980s, even before development of Highly Active Anti-Retroviral Therapy (HAART) used to combat HIV, thousands of lives have been saved.

The difficulty now is that anabolic steroids are becoming much less available legally because of Federal pressure upon producers. The anabolic steroid most successfully used over the years to combat wasting has been nandrolone decanoate. Up until recently, this product was produced by Watson Pharmaceuticals. In 2007, however, Watson stopped producing nandrolone. Instead, it is promoting Oxandrin, an oral steroid that is less effective and has more adverse side effects, but is also proprietary and therefore commands a higher price. Since then, anyone who needs to use nandrolone must go to compounding pharmacies, which will then produce the medicine on a custom order. At this time, the only anabolic steroids that may be used legally in the United States are Oxandrine and nandrolone. So the choice is Watson’s expensive, less effective, propriety product or use of the compounding pharmacies.

This situation presents two major problems for patients who need anabolic therapies. The first is that a prescription filled by a compounding pharmacy is not covered by insurance or AIDS Drug Assistance Programs (ADAPs), so use of nandrolone is an out-of-pocket expense. Many patients suffering from HIV are in difficult economic circumstance. The added expense frequently puts the medicine out of reach.

The other problem is that compounding pharmacies are now under heavy scrutiny by the Drug Enforcement Agency to ensure that prescriptions are for legitimate medical needs. In theory, this would sound reasonable, but, in practice, the added delays, pressure and bureaucratic requirements have caused many compounding pharmacies to shy away from production of nandrolone. The most popular, Applied Pharmacy of Alabama, was providing the product reliably and at a reasonable price. However, the DEA insisted that the pharmacies verify the medical necessity of each prescription. That is not the role of a pharmacy. That is the role of the doctor writing the prescription. So the DEA regularly comes into the Applied Pharmaceuticals, gathers up all their records and keeps them for an unreasonable amount of time for review purposes. This amounts to blatant harassment solely to suppress production of a legitimate medication. For this reason, Applied Pharmacy has announced that it will no longer provide nandrolone or other hormone-based products. Other compounding pharmacies have similarly so halted production, and this has caused an increase in prices among the remaining producers and confusion among HIV prescribers who wrongly assume that nandrolone is no longer available in the U.S.

The result, then, of Representative Waxman’s hearings has been an attack on an important, powerful, beneficial and legal therapy solely because professional athletes use it improperly. Patients with legitimate medical needs should not be made to suffer because of the improper actions of a few. As for young athletes, for which use of anabolic steroids is a concern, I believe that virtually all of the drugs used by them are from black market sources. Legitimate pharmacies filling prescriptions for legitimate medical needs should not be harassed into curtailing production when they are not even the source of the problem.

What I would therefore request is that Representative Waxman hold hearings on the legitimate use of steroids and human growth hormones and the need to ensure that enforcement action against illegal use does not impede appropriate and necessary supplies. I would also ask that efforts be made to publicize these hearing to the same level as those held to highlight improper usage by athletes.

For more information on the impact current actions against anabolic steroids and human growth hormones have had on HIV treatment, I would recommend contacting Nelson Vergel and Michael Mooney, coauthors of Built to Survive, subtitled, “A Comprehensive Guide to the Medical Use of Anabolic Therapies, Nutrition and Exercise for HIV(+) Men and Woman.” This book summarizes all the years of medical research using anabolics to improve health in people with HIV. Mr. Nelson and Mr. Mooney may be contacted through their web site at www.medibolics.com.

Sincerely,

Mark A. Meier

cc: Representative Henry Waxman 2204 Rayburn House Office Building Washington, DC 20515

HIV Lipodystrophy: Where are We After 10 Years?

http://f1.grp.yahoofs.com/v1/EFLdR5ilPaVxAGznd1_SkpO6x-gEAJhwMccdRiItI3tZhDrmSZ-UkqTqOJLUFWeYHpDdtENW6uery9Kibf9Z/lipoupdateGMHCMAR08.pdf

FREE Built to Survive Spanish Translation!

We are happy to announce that the Spanish translation for the main chapters of Built to Survive are now available for free for all Spanish speaking people living with HIV who are dealing with body changes.

Este libro cubre temas sobre terapias anabolicas, testosterona, ejercicio, nutricion y suplementos para aumentar la masa muscular y disminuir la dispodistrofia en el VIH.

El libro esta aqui en el formato adobe acrobat reader ( obtenga adobe reader en adobe.com)
http://f1.grp.yahoofs.com/v1/EFLdRwmeBhxxAGzngylkZa5IgpKxXnsq3yidaK51U0yh5b4l_jbiYCkhCExDzZBrkY8eMTgyLN2rdVFObIX1/Fortaleceteysobrevive.pdf

Hearings on Steroids in Sports and the Impact on Treatments for HIV and other Medical Conditions

March 12, 2008

The Honorable Nancy Pelosi
Speaker of the United State House of Representatives
235 Cannon HOB
Washington, DC 20515

Subject: Representative Henry Waxman’s Hearings on Steroids in Sports and the Impact on Treatments for HIV and other Medical Conditions

Dear Madam Speaker:

The hearings Representative Henry Waxman has been conducting with respect to steroids in sports have had an adverse impact upon treatment for a variety of medical condition for which anabolic steroids and human growth hormones are legitimately and legally used. Among those conditions is HIV, a matter of substantial concern to many in your own district.

The manner in which these hearings have been conducted has created a level of hysteria that has painted all anabolic supplements and medications as unsavory and illegitimate. Certainly illegal use of human growth hormones and steroids in both professional and youth sports is a concern that needs to be addressed. But Representative Waxman’s hearings, as conducted, have highlighted only the negative aspects of such medicine and have not mentioned at all how they are properly and legitimately used and how controls on illegal use should be limited so as not to impact availability for proper usage. I am sure Representative Waxman appreciates the manner in which his name has been prominently highlighted in the press, but members in the HIV community have found him to have little interest in doing anything that will address our concerns in any concrete and demonstrable manner.

Anabolic steroids and recombinant human growth hormone are powerful prescriptive medicines that have been highly effective in treating cancer cachexia, MS, burns and HIV-related wasting and body changes. With respect to HIV, these treatments have been used successfully by thousands of sufferers in combating wasting, a condition which in the past was among the leading causes of death from AIDS. Since use of anabolic steroids and growth hormone to combat wasting began in the late 1980s, even before development of Highly Active Anti-Retroviral Therapy (HAART) used to combat HIV, thousands of lives have been saved.

The difficulty now is that anabolic steroids are becoming much less available legally because of Federal pressure upon producers. The anabolic steroid most successfully used over the years to combat wasting has been nandrolone decanoate. Up until recently, this product was produced by Watson Pharmaceuticals. In 2007, however, Watson stopped producing nandrolone. Instead, it is promoting Oxandrine, an oral steroid that is less effective and has more adverse side effects, but is also proprietary and therefore commands a higher price. Since then, anyone who needs to use nandrolone must go to compounding pharmacies, which will then produce the medicine on a custom order. At this time, the only anabolic steroids that may be used legally in the United States are Oxandrine and nandrolone. So the choice is Watson’s expensive, less effective, propriety product or use of the compounding pharmacies.

This situation presents two major problems for patients who need anabolic therapies. The first is that a prescription filled by a compounding pharmacy is not covered by insurance or AIDS Drug Assistance Programs (ADAPs), so use of nandrolone is an out-of-pocket expense. Many patients suffering from HIV are in difficult economic circumstance. The added expense frequently puts the medicine out of reach.

The other problem is that compounding pharmacies are now under heavy scrutiny by the Drug Enforcement Agency to ensure that prescriptions are for legitimate medical needs. In theory, this would sound reasonable, but, in practice, the added delays, pressure and bureaucratic requirements have caused many compounding pharmacies to shy away from production of nandrolone. The most popular, Applied Pharmacy of Alabama, was providing the product reliably and at a reasonable price. However, the DEA insisted that the pharmacies verify the medical necessity of each prescription. That is not the role of a pharmacy. That is the role of the doctor writing the prescription. So the DEA regularly comes into the Applied Pharmaceuticals, gathers up all their records and keeps them for an unreasonable amount of time for review purposes. This amounts to blatant harassment solely to suppress production of a legitimate medication. For this reason, Applied Pharmacy has announced that it will no longer provide nandrolone or other hormone-based products. Other compounding pharmacies have similarly so halted production, and this has caused an increase in prices among the remaining producers and confusion among HIV prescribers who wrongly assume that nandrolone is no longer available in the U.S.

The result, then, of Representative Waxman’s hearings has been an attack on an important, powerful, beneficial and legal therapy solely because professional athletes use it improperly. Patients with legitimate medical needs should not be made to suffer because of the improper actions of a few. As for young athletes, for which use of anabolic steroids is a concern, I believe that virtually all of the drugs used by them are from black market sources. Legitimate pharmacies filling prescriptions for legitimate medical needs should not be harassed into curtailing production when they are not even the source of the problem.

What I would therefore request is that Representative Waxman hold hearings on the legitimate use of steroids and human growth hormones and the need to ensure that enforcement action against illegal use does not impede appropriate and necessary supplies. I would also ask that efforts be made to publicize these hearing to the same level as those held to highlight improper usage by athletes.

For more information on the impact current actions against anabolic steroids and human growth hormones have had on HIV treatment, I would recommend contacting Nelson Vergel and Michael Mooney, coauthors of Built to Survive, subtitled, “A Comprehensive Guide to the Medical Use of Anabolic Therapies, Nutrition and Exercise for HIV(+) Men and Woman.” This book summarizes all the years of medical research using anabolics to improve health in people with HIV. Mr. Nelson and Mr. Mooney may be contacted through their web site at www.medibolics.com.

Sincerely,

Mark A. Meier

cc: Representative Henry Waxman
2204 Rayburn House Office Building
Washington, DC 20515

Close to a cure for AIDS?

From:
http://www.aidsmeds.com/articles/hiv_aids_stemcell_2042_14199.shtml

Transplanting Hope: Stem Cell Experiment Raises Eyebrows at CROI

March 11, 2008

By David Evans

Not every remarkable HIV treatment discovery makes the front page of the morning papers. Take, for example, a single-patient study presented at the 15th annual Conference on Retroviruses and Opportunistic Infections (CROI) in Boston that went largely unnoticed by news outlets but is now generating excitement among activists and researchers.

The intriguing study involves an HIV-positive German man with leukemia who has regrown a new immune system after receiving a stem cell transplant and has since kept his viral load undetectable. In fact, sensitive tests have been unable to detect the virus in the patient’s blood or tissues. According to the CROI report, presented by Gero Hütter, MD, of the Medical University of Berlin and his colleagues, the key to the transplant’s success was the stem cells provided by a donor whose immune system was genetically resistant to HIV infection.

Nobody, least of all the authors of the study, is using the “c” word to describe the results. What’s more, stem cell transplants are hardly ready for prime time, given that it is first necessary to destroy a person’s existing immune system with a potentially lethal course of chemotherapy and radiation to make room for the new cells, at a cost of up to $250,000. Yet the study has generated a great deal of interest among some who are familiar with it. Top AIDS researcher Michael Lederman, MD, a professor of medicine at Case Western Reserve University in Cleveland, says, “I think this is really exciting.”

Others, such as staff scientist Tae-wook Chun, PhD, of the National Institute of Allergy and Infectious Diseases (NIAID), in Bethesda, Maryland, caution that the experiment may not amount to a breakthrough. He says, “It’s interesting, but the bigger picture is that doing stem cell transplants is not a realistic approach for curing AIDS.”

Such caution may be warranted. After all, researchers have been saying for twenty-five years that we’re just ten years away from an effective vaccine. But activists like Richard Jefferys, from New York City’s Treatment Action Group (TAG), argue that it’s vital for researchers and advocates not to overlook hopeful research findings such as this one, or give up on the possibility of a cure. “I think it’s well worth shining a spot light on,” says Jefferys. “[People living with HIV and activists] have to be the ones pushing back a little bit and saying that life-long therapy is fine for now but we can do better.”

Rebirth of an HIV-resistant immune system

“Doing better” is just what Dr. Hütter had in mind when confronted with the need to perform a stem cell transplant on his patient, a 40-year-old HIV-positive man diagnosed with acute myeloid leukemia, a potentially fatal cancer of the immune system. Rather than simply performing a transplant that would increase the patient’s chance of cancer survival, Dr. Hütter’s group decided to go for double or nothing and attempt a transplant that would also increase the patient’s chances of surviving HIV.

All that was required was a simple phone call. He asked the blood and tissue bank if any of their stem cell donors had a particular genetic defect, called the CCR5 delta-32 deletion. This defect prevents CD4 cells from developing a receptor, called CCR5, on their surfaces. People who inherit this genetic mutation from both parents have CD4 cells that lack the CCR5 entirely and, as a result, are highly resistant to infection with HIV. People who inherit the mutation from one parent can be infected, but because they have fewer CCR5 receptors on their CD4 cells, tend to have slower disease progression. Dr. Hütter found a very lucky match—a suitable donor with the delta-32 deletion from both parents.

As is standard in stem cell transplants, Dr. Hütter’s team prepared the patient to receive the cells by first ablating, or destroying, most of his immune cells. This process, also called conditioning, is usually performed using intensive chemotherapy and radiation. As Dr. Lederman explains it, “You need to make room [for new immune cells to grow].”

Conditioning can be a brutal process. It requires a lengthy hospitalization and can cause numerous and potentially life-threatening side effects. This is part of the reason that stem cell transplants for conditions like leukemia are typically only performed when patients have failed to respond to standard treatment. The other reason is the cost, which in the United States typically ranges from $100,000 to $250,000.

The Berlin stem cell transplant has been a success so far. According to Dr. Hütter, the patient’s immune system has not rejected the transplant. In fact, 100 percent of his post-treatment immune system cells were grown out from the transplanted stem cells. Nor has there been a return of the leukemia, though this is always a possibility, even following a successful stem cell transplant.

Most exciting is the fact that the patient, who went off of his antiretroviral medication for the transplant procedure, has been able to remain off of the drugs for more than 285 days. Moreover, when the researchers looked for evidence of virus in blood and rectal tissue biopsies, not only was his viral load undetectable, more sensitive methods for detecting viral particles, known as proviral DNA, were also unable to find evidence of HIV.

Cautious optimism or reckless hope?

Experts stress that it is far too early to call the experiment a cure. For one thing, post-transplant survival in people who are battling leukemia is far from a sure thing. And as Chun points out, an immune system with CD4 cells lacking the CCR5 receptor is still susceptible to virus that uses another receptor dubbed CXCR4. If the German transplant patient has CXCR4-using virus anywhere in his body, it can potentially reseed his immune system with HIV.

Chun, who is working on techniques for eradicating HIV in the laboratory of NIAID director Anthony Fauci, MD, has good reason to be cautious. It was not long after researcher David Ho claimed in 1996 that protease inhibitors had given us the tool to eradicate HIV that we learned of the virus’ ability to hide out for years in the immune system, meaning that antiretroviral therapy, at least as we currently know it, is a lifelong proposition for most people with HIV.

Dr. Lederman, on the other hand, takes a more optimistic view. Despite the dangers and costs associated with stem cell transplants, he says it may be worthwhile to consider the procedure in people with HIV who do not otherwise require a transplant, such as for leukemia, but in whom none of the current or experimental antiretrovirals are working and who have low CD4 counts and uncontrolled virus. “I think such an approach is entirely defensible, especially in light of this experiment that we see here,” says Lederman.

When asked if he is planning additional experiments in other patients with HIV and leukemia, Dr. Hütter says while such patients are rare, he would certainly consider it.

Dr. Lederman also believes that if Dr. Hütter’s experiment continues to look successful, it could have implications for other experimental approaches that wouldn’t require the dangers of a stem cell transplant. Dr. Lederman points to technologies like gene therapy and “RNA silencing” as promising methods for artificially knocking out the delta-32 gene responsible for producing CCR5 receptors.

Inspired by such experiments are non-profit groups like the Linda Grinberg Foundation for AIDS and Immune Research (FAIR). Martin Delaney, a long time AIDS activist and the current president of FAIR, says that he and other groups are planning a conference for the end of the year to chart out the scientific steps that may open up the path to a cure. According to Delaney, FAIR and the Foundation for AIDS Research (amfAR) are very interested in studies like Dr. Hütter’s and plan to make grants to scientists who propose research that will take us down that path.

Delaney, who was among the first people to notice Dr. Hütter’s poster at CROI and point it out to other activists and researchers, remains steadfast in his hope about a cure, a hope that some may consider fruitless. Although he refuses to respond to experiments like Dr. Hütter’s with pessimism, Delaney does understand the caution with which most researchers greet such proof-of-concept studies. He says, “I understand that [caution], because they’re case studies, rather than controlled clinical trials. But I think that’s where the cure is going to first appear. It’s not going to appear out of a controlled trial.”

Liver Warning with Prezista

Tibotec Dear Healthcare Professional:

IMPORTANT DRUG WARNING

March 2008
Dear Healthcare Professional:

Tibotec Therapeutics, in cooperation with the U.S. Food and Drug Administration, would like to inform you of an important update to the prescribing information for PREZISTA TM (darunavir) tablets regarding addition of a Warning on Hepatotoxicity.

In clinical trials and postmarketing experience, drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported in patients receiving combination therapy with PREZISTA/rtv. Given the clinical relevance of this adverse reaction, the following information on hepatotoxicity has been added to the WARNINGS section of the PREZISTA Prescribing Information:

WARNINGS:

Hepatotoxicity

Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA/rtv. During the clinical development program (N=3063), hepatitis has been reported in 0.5% of patients receiving combination therapy with PREZISTA/rtv. Patients with preexisting liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities including severe hepatic adverse events.

Post-marketing cases of liver injury, including some fatalities, have been reported. These have generally occurred in patients with advanced HIV-1 disease taking multiple concomitant medications, having comorbidities including hepatitis B or C coinfection, and/or developing immune reconstitution syndrome.
A causal relationship with PREZISTA/rtv therapy has not been established.

Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA/rtv and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pretreatment elevations of transaminases, especially during the first several months of PREZISTA/rtv treatment.

If there is evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on PREZISTA/rtv, interruption or discontinuation of treatment must be considered.

In addition, the Adverse Reaction section of the PREZISTA Prescribing Information and the Patient Package Insert have been updated to include this new information.

Enclosed, please find the updated Prescribing Information as well as the Patient Package Insert.

Please see PREZISTA Indication and additional Important Safety Information included on page 3 and page 4 of this letter.

Tibotec Therapeutics is committed to ensuring that PREZISTA is used safely and effectively and providing you with the most current information for our products.

Should you have any questions, require further information on product safety, or wish to report adverse patient experiences, please contact Tibotec Therapeutics Medical Information at 1-877REACH TT (1-877-732-2488).

Alternatively, adverse events may be reported to FDA’s MedWatch reporting system
o By phone (1800FDA1088), by facsimile (1800FDA0178),
o Online (https://www.accessdata.fda.gov/scripts/medwatch/) or
o Mailed, using the MedWatch for FDA 3500 postage paid form, to the FDA Medical Products Reporting Program, 5600 Fishers Lane, Rockville, MD 208529787

Sincerely,

Alan Tennenberg, MD, MPH
Vice President, Clinical Affairs

FDA Issues New Prezista (Darunavir) Label Changes

Label attached; A Dear Doctor Letter from Tibotec follows below.

Updates have been made to Prezista (darunavir) tablets labeling to reflect significant new risk information. Changes have been made to the CLINICAL PHARMACOLOGY section to include data from 6 pharmacokinetic, drug interaction Phase 1 trials, and to the WARNINGS, PRECAUTIONS AND ADVERSE REACTIONS sections of the package insert to include hepatotoxicity information. Other updates include those made to PRECAUTIONS, updates to DOSAGE AND ADMINISTRATION, and changes to Table 11 to include information regarding a potential drug-drug interaction with rosuvastatin.

In the WARNINGS section, the following has been added:

“Hepatotoxicity
Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA/rtv. During the clinical development program (N=3063), hepatitis has been reported in 0.5% of patients receiving combination therapy with PREZISTA/rtv. Patients with preexisting liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities including severe hepatic adverse events.

Post-marketing cases of liver injury, including some fatalities, have been reported. These have generally occurred in patients with advanced HIV-1 disease taking multiple concomitant medications, having co-morbidities including hepatitis B or C co-infection, and/or developing immune reconstitution syndrome. A causal relationship with PREZISTA/rtv therapy has not been established.

Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA/rtv and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pre-treatment elevations of transaminases, especially during the first several months of PREZISTA/rtv treatment.

If there is evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on PREZISTA/rtv, interruption or discontinuation of treatment must be considered.”

The PRECAUTIONS section has been changed to read as follows:

“Patients with co-existing conditions
Hepatic Impairment: No dose adjustment of PREZISTA/rtv is necessary for patients with either mild or moderate hepatic impairment. There are no pharmacokinetic or safety data available for subjects with severe hepatic impairment, therefore, PREZISTA/rtv is not recommended for use in patients with severe hepatic impairment (see CLINICAL PHARMACOLOGY, Pharmacokinetics in Adults, Special Populations, Hepatic Impairment and DOSAGE AND ADMINISTRATION).”

Table 11, Established and Other Potentially Significant Drug Interactions, has been modified, under HMG-CoA Reductase Inhibitors, to include rosuvastatin, indicating increased concentration of rosuvastatin, with the following clinical comment: “Use the lowest possible dose of atorvastatin, pravastatin or rosuvastatin with careful monitoring, or consider other HMG-CoA reductase inhibitors such as fluvastatin in combination with PREZISTA/rtv.”

The following sentence has been added to the CLINICAL PHARMACOLOGY section, under Absorption and Bioavailabilty: “In vivo data suggests that darunavir/ritonavir is an inhibitor of the p-glycoprotein (p-gp) transporters.”

The following has been added under: Special Populations
“Hepatic Impairment: Darunavir is primarily metabolized by the liver. The steady-state pharmacokinetic parameters of darunavir were similar after multiple dose co-administration of PREZISTA/rtv 600/100 mg b.i.d. to subjects with normal hepatic function (n=16), mild hepatic impairment (Child-Pugh Class A, n=8), and moderate hepatic impairment (Child-Pugh Class B, n=8). The effect of severe hepatic impairment on the pharmacokinetics of darunavir has not been evaluated (see PRECAUTIONS, Patients with co-existing conditions, Hepatic Impairment and DOSAGE AND ADMINISTRATION).”

In addition, there are updates to Table 4: Drug Interactions Pharmacokinetic Parameters for Darunavir in the Presence of Co-administered Drugs, and Table 5: Drug Interactions: Pharmacokinetic Parameters for Co-administered Drugs in the Presence of Darunavir/Ritonavir.

The last paragraph of the ADVERSE REACTIONS section now reads: “Patients co-infected with hepatitis B and/or hepatitis C virus: In subjects co-infected with hepatitis B or C virus receiving PREZISTA/rtv, the incidence of adverse events and clinical chemistry abnormalities was not higher than in subjects receiving PREZISTA/rtv who were not co-infected, except for increased hepatic enzymes (see WARNINGS, Hepatotoxicity). The pharmacokinetic exposure in co-infected subjects was comparable to that in subjects without co-infection.”

In addition, the following has been added:

“Additional adverse reactions identified in clinical studies, occurring in less than 1% of the patients, are listed below by body system:

Hepatobiliary System: acute hepatitis, cytolytic hepatitis, hepatotoxicity, hyperbilirubinemia

Skin and Appendages: erythema multiforme, Stevens-Johnson Syndrome
[this duplicate information was deleted from the Skin and Appendages section under the treatment-emergent adverse events occurring in less than 2% of de novo subjects]”

Changes were also made to DOSAGE AND ADMINISTRATION, to include the following: “Hepatic Impairment: No dose adjustment is required in patients with mild or moderate hepatic impairment. There are no data regarding the use of PREZISTA/rtv when co-administered to subjects with severe hepatic impairment; therefore, PREZISTA/rtv is not recommended for use in patients with severe hepatic impairment (see CLINICAL PHARMACOLOGY, Pharmacokinetics in Adults, Special Populations, Hepatic Impairment and PRECAUTIONS, Patients with co-existing conditions, Hepatic Impairment).”

The new label will be posted soon at DailyMed to replace the 08/2007 version.

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration