VIRACEPT(R) Studies Suggest No Apparent Increase in Birth Defects And Drug Levels Boosted When Taken With Food
Thursday February 13, 1:30 pm ET
BOSTON, Feb. 13 /PRNewswire-FirstCall/ -- A study presented by Agouron Pharmaceuticals, Inc., a Pfizer Company (NYSE: PFE - News) today at the 10th Conference on Retroviruses and Opportunistic Infections in Boston indicated that there was no apparent increase in the established risk of overall birth defects with the use of VIRACEPT® (nelfinavir mesylate). A separate study presented showed that taking VIRACEPT with a moderate calorie, low fat meal and a high calorie, high fat meal boosts drug levels three to five times compared to taking it without food.
Implications for Use in Pregnant Women
The first study presented by Susan Conner et al found that among 301 first trimester exposures to VIRACEPT, there were nine birth defects -- a prevalence of 3.0 percent, which does not differ from that of the general population according to the Centers for Disease Control (3.1 per 100 live births). For this study, investigators extracted from the Antiretroviral Pregnancy Registry (APR) all pregnancies which had been exposed to VIRACEPT -- used alone or in combination with other antiretroviral agents. A sufficient number of patients with a first trimester exposure to VIRACEPT were enrolled in order to detect a two-fold increase in the risk of overall birth defects. No apparent increase in risk was detected.
"Given that approximately 30 percent of new HIV infections occur in women(1), it is critical to assess prenatal exposures to antiretroviral therapy," commented APR Project Manager, Deborah Covington, DrPH, Senior Epidemiologist, PharmaResearch Corporation. "Currently, the CDC treatment guidelines recommend antiretroviral therapy for all HIV-infected pregnant women to reduce the risk of transmitting the HIV virus to the baby, so the findings from this study are noteworthy and provide some assurance for pregnant women taking nelfinavir."
The APR, which is designed to monitor prenatal exposures to antiretroviral therapy and detect any potential increase in the risk of birth defects, uses a prospective exposure-registration cohort design. Healthcare providers log pregnant women with prenatal exposures to any antiretroviral therapy, report data on exposure throughout pregnancy, and provide birth outcome data in this registry. VIRACEPT was the most commonly reported protease inhibitor in pregnancy according to APR data. Through July 2002, the APR has monitored 915 live births exposed to VIRACEPT. The Antiretroviral Pregnancy Registry is ongoing; exposures to all antiretroviral therapies during pregnancy may be reported by calling 800-258-4263. However, there are no adequate and well- controlled studies in pregnant women. VIRACEPT should be used during pregnancy only if clearly needed.
Effect of Food Intake on Pharmacokinetic Parameters
Another study, presented by Dr. Carolyn Petersen et al found that food intake has a marked effect on VIRACEPT pharmacokinetics (PK) with the highest drug levels achieved at the highest food intake. This study found that meals containing 500 to 1000 kilocalories and 20 to 50 percent fat achieved area- under-the-curve (AUC) values from three to five times those achieved in the fasting state. An example of a meal containing 500 kilocalories and 20 percent fat is: 8 fluid ounces of orange juice, 4 ounces of Dannon Light yogurt, 1 cup of Cheerios, 8 fluid ounces of 2% milk, and 1 slice of wheat toast with 1 teaspoon of butter. This is the meal given in this study. Furthermore, metabolite (M8) concentrations rose with increasing food intake, but the percentage relative to VIRACEPT remained the same, at approximately 15 to 20 percent.
"The data observed in this initial study offer significant insights and provide a foundation for further study on the effect of food and fat intake on steady state pharmacokinetics in people with HIV," observed Dr. Carolyn Petersen, Medical Director, Agouron Pharmaceuticals, Inc., A Pfizer Company. "It is important to understand how to optimize drug levels as that may correlate to effectiveness and our ability to control the virus."
This phase 1, randomized, open-label, four-way crossover study evaluated the impact of total kilocalories and fat content on single-dose PK parameters of the 250 mg tablet formulation of VIRACEPT in 24 normal healthy volunteers. Study participants were dosed with 1250 mg of VIRACEPT four times at one-week intervals and 12 hour PK was collected following each of these doses. Each participant was assigned four food intakes (fasting, 125 kilocalories with 20 percent fat, 500 kilocalories with 20 percent fat, and 1000 kilocalories with 50 percent fat) prior to dosing.
VIRACEPT, in combination with other anti-retroviral agents, is indicated for the treatment of HIV infection. The recommended dosage for VIRACEPT is 1,250 mg (five 250 mg tablets) twice a day or 750 mg (three 250 mg tablets) three times daily. VIRACEPT has been shown to be generally well tolerated. The most commonly reported side effect attributable to VIRACEPT is diarrhea.
VIRACEPT is metabolized primarily by the liver. Therefore, caution should be exercised when administering VIRACEPT tablets to patients with impaired hepatic function. Redistribution or accumulation of body fat may occur in patients receiving anti-retroviral therapy. The cause and long-term health effects of these conditions are not known at this time. Increased bleeding in patients with hemophilia, as well as diabetes mellitus and hyperglycemia, has been reported with protease inhibitors.
VIRACEPT should not be used with certain medications. Taking certain other prescription and nonprescription drugs and supplements with VIRACEPT could create the potential for serious side effects that could be life threatening. In addition, some drugs may markedly reduce VIRACEPT plasma concentrations, resulting in suboptimal antiviral activity and subsequent emergence of drug resistance. Patients should always talk to their physician or healthcare provider before starting new medicines. HIV drugs do not cure HIV infection or prevent individuals from spreading the virus.
Agouron Pharmaceuticals, Inc. became a wholly owned subsidiary of Pfizer Inc in 2000. Pfizer Inc discovers, develops, manufactures and markets leading prescription medicines, for humans and animals, and many of the world's best known over-the-counter consumer brands.
For more information, dial toll free 1-888-VIRACEPT (847-2237).
VIRACEPT® and Agouron® are registered trademarks of Agouron Pharmaceuticals, Inc.
(1) HIV/AIDS Update, Centers for Disease Control and Prevention,
cdc.gov.
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Source: Agouron Pharmaceuticals, Inc. |
