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FDA Approves Fixed Dose Combination Tablet That Contains Three Nucleoside Reverse Transcriptase Inhibitors

RESEARCH TRIANGLE PARK, N.C., May 16 /PRNewswire/ -- GlaxoSmithKline (GSK) today announced that the U.S. Food and Drug Administration (FDA) has granted traditional approval status to TRIZIVIR(R) (abacavir sulfate, lamivudine, and zidovudine) for the treatment of HIV infection. TRIZIVIR is a fixed-dose- combination tablet containing the three nucleoside reverse transcriptase inhibitors EPIVIR(R) (lamivudine, 3TC), RETROVIR(R) (zidovudine, ZDV) and ZIAGEN(R) (abacavir sulfate, ABC). The FDA grants traditional approval for a medication based on data from clinical trials of 48 weeks or more. Accelerated approval, which requires fewer weeks of data for drugs that will meet unmet medical needs, was granted to TRIZIVIR in 2000, based on analysis of 24-week data. TRIZIVIR in combination with other antiretroviral agents or alone, is indicated for the treatment of HIV infection. TRIZIVIR is one of multiple products containing abacavir sulfate, also know as ZIAGEN. Before starting a patient on TRIZIVIR, physicians should review medical history for prior exposure to any abacavir-containing product in order to avoid reintroduction in a patient with a history of hypersensitivity to abacavir. Limited data exist on the use of TRIZIVIR alone in patients with higher baseline viral loads (>100,000 copies/mL).

"TRIZIVIR is the first and only FDA-approved, fixed-dose-combination drug for HIV that combines three drugs into one tablet and it exemplifies GlaxoSmithKline's commitment to help simplify HIV regimens for patients," said Doug Manion, M.D., vice president for HIV Clinical Research for the Infectious Diseases Medicines Development Center (MDC) for GSK. "TRIZIVIR and its components are well studied and well known to physicians and patients, with approximately 40,000 patients in the U.S. now taking TRIZIVIR."

TRIZIVIR is dosed as a single tablet, twice a day, with no food or water restrictions and can be used in combination with other antiretroviral agents or alone. The use of TRIZIVIR in therapy-naive adults may preserve the use of other classes of antiretroviral agents for the future.

TRIZIVIR is also available in a dispensing carton called the TRIZIVIR Convenience Pack. Each Convenience Pack contains 60 TRIZIVIR Tablets on a blister strip, providing patients with a tear-off roll for twice-daily tablet dosing. The Convenience Pack also provides patients with a dosage calendar to help them keep track of when they take their medication and alert them when a refill is needed.

GSK markets two other fixed-dose-combination tablets, each containing two antiretroviral medications: COMBIVIR(R) (lamivudine and zidovudine), which is a combination of EPIVIR plus RETROVIR and EPZICOM(TM) (abacavir sulfate and lamivudine), which is a combination of EPIVIR plus ZIAGEN.

Product Information
HIV medicines do not cure HIV infection/AIDS or prevent passing HIV to others.

TRIZIVIR was the first and remains the only FDA-approved HIV drug therapy that combines three nucleoside reverse transcriptase inhibitors (NRTIs) into one tablet. TRIZIVIR is indicated in combination with other antiretroviral agents or alone for the treatment of HIV-1 infection. TRIZIVIR is one of multiple products containing abacavir sulfate, also known as ZIAGEN. Before starting a patient on TRIZIVIR, physicians should review medical history for prior exposure to any abacavir-containing product in order to avoid reintroduction in a patient with a history of hypersensitivity to abacavir.

Limited data exist on the use of TRIZIVIR alone in patients with higher baseline viral load levels (>100,000 copies/mL). The daily dosing recommendation for TRIZIVIR is one tablet taken twice daily, with or without food or water.

Abacavir has been associated with serious and sometimes fatal hypersensitivity reactions. Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in two or more of the following groups: 1) fever, 2) rash, 3) gastrointestinal symptoms, including nausea, vomiting, diarrhea or abdominal pain, 4) constitutional symptoms, including generalized malaise, fatigue or achiness and/or 5) respiratory symptoms such as dyspnea, cough or pharyngitis. Symptoms of this reaction usually occur within the first six weeks of treatment although these reactions can occur at any time during therapy.

To avoid a delay in diagnosis and minimize the risk of a life-threatening hypersensitivity reaction, discontinue TRIZIVIR as soon as a hypersensitivity reaction is suspected. Discontinue TRIZIVIR if hypersensitivity cannot be ruled out, even when other diagnoses are possible (e.g., acute onset respiratory disease, gastroenteritis, or reactions to other medication). Following a hypersensitivity reaction to abacavir, never restart TRIZIVIR or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death. Reintroduction of TRIZIVIR or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions. Such reactions can occur within hours. A Medication Guide and Warning Card for abacavir-containing products must be provided by the pharmacists to the patient with each new and refill prescription in order to provide further information to the patient on this drug.

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with hepatitis B virus (HBV) and HIV and have discontinued lamivudine, which is one component in TRIZIVIR. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue TRIZIVIR and are coinfected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted (see Warnings).

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.

Zidovudine 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.

Redistribution/accumulation of body fat has been observed in patients receiving antiretroviral therapy. The causal relationship, mechanism and long- term consequences of these events are currently unknown.

The most common adverse events (>/=5%) of at least moderate intensity associated with the use of TRIZIVIR include nausea, headache, malaise and fatigue, nausea and vomiting, hypersensitivity reaction, diarrhea, fever and/or chills, depressive disorders, musculoskeletal pain, skin rashes, ear/nose/throat infections, viral respiratory infections, and anxiety.

Isolates containing abacavir resistance-associated mutations, namely, K65R, L74V, Y115F and M184V, exhibited cross resistance to didanosine, emtricitabine, lamivudine, tenofovir and zalcitabine in vitro and in patients.

At A Glance
-- The three-drug combination tablet TRIZIVIR has received traditional approval status from the U.S. FDA to treat HIV infection, in combination with other antiretrovirals or alone.

-- TRIZIVIR combines three drugs into one tablet that is taken twice a day and may simplify treatment for some people with HIV.

-- Currently there are approximately 40,000 patients in the U.S. on TRIZIVIR.

Source: GlaxoSmithKline

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