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| |  FDA Approves Anti-HIV Drug, Trizivir (Lamivudine, Zidovudine And Abacavir) RESEARCH TRIANGLE PARK, NC -- November 15, 2000 -- Trizivir, a new product that combines three anti-HIV medicines into one single tablet, has been approved by the Food and Drug Administration. This marks an important advance for dosing of combination drug regimens. Patients for whom Trizivir is prescribed will now be able to take this three-drug HIV medicine as one tablet twice a day. Trizivir® Tablets combine the two widely used HIV medications Epivir® (lamivudine), also known as 3TC, and Retrovir® (zidovudine; AZT), along with Ziagen® (abacavir sulfate), and is the first product to combine three antiretroviral drugs into a single tablet. (Epivir and Retrovir are already available in a dual combination product, Combivir® (lamivudine/zidovudine).) Trizivir can be taken as one tablet in the morning and one tablet in the evening without regard to food or water intake. Trizivir is indicated alone or in combination with other antiretroviral agents for the treatment of HIV infection and it is intended only for patients whose regimen would otherwise include abacavir, lamivudine, and zidovudine. This indication is based on analyses of surrogate markers in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long-term suppression of HIV RNA or disease progression with Trizivir. There are limited data on the use of this triple-combination regimen in patients with higher viral loads (>100,000 copies/mL) at baseline. Because it is a fixed-dose tablet, Trizivir should not be prescribed for adults or adolescents who weigh less than 40 kilograms (approximately 88 pounds) or other patients requiring dose adjustment (such as patients with impaired renal function or patients experiencing dose-limiting side effects). The most serious adverse event associated with abacavir (a medicine in Trizivir and Ziagen) is a hypersensitivity reaction that can be life threatening and has been fatal in some cases. It is characterized by fever, skin rash, fatigue and gastrointestinal symptoms, such as nausea, vomiting, diarrhea or abdominal pain. Respiratory symptoms such as dyspnea, pharyngitis or cough may also occur. In clinical studies, hypersensitivity reaction has been observed in approximately 5 percent of patients. The diagnosis of hypersensitivity reaction should be carefully considered for patients presenting with symptoms of acute respiratory diseases, even if alternative respiratory diagnoses (pneumonia, bronchitis, flu-like illness) are possible. Therefore, patients and health care professionals should also watch for respiratory symptoms such as shortness of breath, sore throat or cough. To avoid a delay in diagnosis and minimize the risk of a life-threatening hypersensitivity reaction, Trizivir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible (e.g., acute onset respiratory disease, gastroenteritis, or reactions to other medication). Rechallenge is contraindicated after a diagnosis of hypersensitivity. Symptoms of this reaction usually occur within the first six weeks of treatment although these reactions may occur at any time during therapy. The symptoms of this reaction get progressively worse with continued treatment with abacavir (Trizivir or Ziagen), but generally resolve following permanent discontinuation of Trizivir or Ziagen. Patients experiencing these symptoms should stop taking Trizivir or Ziagen and contact a physician immediately. Patients experiencing this reaction must not take Trizivir or Ziagen again as restarting the drug after a hypersensitivity reaction has resulted in cases of life-threatening and fatal reactions. When therapy with Trizivir or Ziagen has been discontinued and reinitiation of therapy is under consideration, the reason for discontinuation should be evaluated to ensure that the patient did not have a hypersensitivity reaction. A Medication Guide and Warning Card for Trizivir or Ziagen must be provided by the pharmacist to the patient with each new and refill prescription in order to provide further information to the patient on this drug. A person who has taken Ziagen and experienced a hypersensitivity reaction must not take Trizivir or Ziagen. Patients who are receiving the triple nucleoside regimen of Combivir + Ziagen will now have the option of taking their entire regimen in one tablet of Trizivir twice a day. "Trizivir offers some patients the possibility of a regime as simple as one pill twice a day. For others, it offers them the possibility of simplifying the rest of their existing regimen," said Peter J. Ruane, MD of Tower Infectious Diseases Medical Associates Inc. in Los Angeles, CA. Many people being treated for HIV take as many as 20 tablets or capsules per day. Some of these drugs may have food or water restrictions or requirements, or require complicated multiple dosings throughout the day. "There are two main benefits of Trizivir. The first is it provides simplification of dosing. So they're getting three anti-retroviral medicines in a single tablet taken twice a day. The second benefit is that you can take that single tablet without any restrictions around food or water. So you don't have to take it with a meal, you can take it with a meal if you want to, and you don't have to drink volumes of water while you're on this medicine," said Amy Keller, International Project Team Leader for Trizivir at Glaxo Wellcome. Glaxo Wellcome was the first company to develop a product combining two antiretroviral medications into one tablet. Combivir, available in the US since 1997, is a double-nucleoside foundation of many combination drug regimens in the treatment of HIV today. Data from a study of Trizivir have established its bioequivalence to the separate doses of the medicines, Ziagen, Epivir and Retrovir. It was also shown that coadministration with food had no effect on the pharmacokinetics of Trizivir. Trizivir has a low likelihood of interactions with antiretroviral drugs that are metabolized by the cytochrome P450 enzyme system. This is a favorable factor when trying to prescribe the multi-drug regimens required to treat HIV. In clinical trials when Ziagen was taken, primarily with Epivir and Retrovir -- the components of Trizivir -- the most commonly reported adverse events were nausea (47 percent), nausea and vomiting (16 percent), diarrhea (12 percent), loss of appetite/anorexia (11 percent), and insomnia and other sleep disorders (7 percent). Zidovudine, one of the three active ingredients in Trizivir, has been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced HIV disease. Prolonged use of zidovudine has been associated with symptomatic myopathy. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, zidovudine, lamivudine, and other antiretrovirals. The individual components of Trizivir will continue to be available as Combivir, Epivir, Retrovir and Ziagen in their existing formulations. Ziagen was discovered and developed by Glaxo Wellcome. The rights to related compounds and technology, including intermediates used in the manufacture of Ziagen, resulting from the research by Dr. Robert Vince, et. al, were licensed to Glaxo Wellcome by the University of Minnesota. Epivir was discovered by scientists at BioChem Pharma of Laval, Quebec, Canada, and was licensed to Glaxo Wellcome in 1990. Glaxo Wellcome is a pharmaceutical industry leader in HIV research and therapies. Glaxo Wellcome manufactures and markets the widely used anti-HIV medicines Combivir, Epivir, Retrovir, Ziagen and the protease inhibitor Agenerase(R) (amprenavir). Related Links: Glaxo Wellcome and BioChem Pharma.
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