Dosage Forms and Strengths• Retrovi

Dosage Forms and Strengths

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Retrovir capsules 100 mg (white, opaque cap and body) containing 100 mg zidovudine and printed with “Wellcome” and unicorn logo on cap and “Y9C” and “100” on body.
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Retrovir syrup (colorless to pale yellow, strawberry‑flavored) containing 10 mg zidovudine in each mL.
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Retrovir injection is a clear, nearly colorless, sterile aqueous solution with a pH of approximately 5.5. Each vial contains 200 mg of zidovudine in 20 mL solution (10 mg per mL).

Contraindications

Retrovir is contraindicated in patients who have had a potentially life-threatening hypersensitivity reaction (e.g., anaphylaxis, Stevens-Johnson syndrome) to any of the components of the formulations.
Warnings and Precautions
Hematologic Toxicity/Bone Marrow Suppression

Retrovir should be used with caution in patients who have bone marrow compromise evidenced by granulocyte count less than 1,000 cells per mm3 or hemoglobin less than 9.5 g per dL. Hematologic toxicities appear to be related to pretreatment bone marrow reserve and to dose and duration of therapy. In patients with advanced symptomatic HIV-1 disease, anemia and neutropenia were the most significant adverse events observed. In patients who experience hematologic toxicity, a reduction in hemoglobin may occur as early as 2 to 4 weeks, and neutropenia usually occurs after 6 to 8 weeks. There have been reports of pancytopenia associated with the use of Retrovir, which was reversible in most instances after discontinuance of the drug. However, significant anemia, in many cases requiring dose adjustment, discontinuation of Retrovir, and/or blood transfusions, has occurred during treatment with Retrovir alone or in combination with other antiRetrovirals.

Frequent blood counts are strongly recommended to detect severe anemia or neutropenia in patients with poor bone marrow reserve, particularly in patients with advanced HIV-1 disease who are treated with Retrovir. For HIV-1-infected individuals and patients with asymptomatic or early HIV-1 disease, periodic blood counts are recommended. If anemia or neutropenia develops, dosage interruption may be needed [see Dosage and Administration (2.4)].
Latex

The vial stoppers for Retrovir injection contain natural rubber latex which may cause allergic reactions in latex-sensitive individuals.
Myopathy

Myopathy and myositis with pathological changes, similar to that produced by HIV-1 disease, have been associated with prolonged use of Retrovir.
Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including zidovudine and other antiRetrovirals. A majority of these cases have been in women. Obesity and prolonged exposure to antiRetroviral nucleoside analogues may be risk factors. Particular caution should be exercised when administering Retrovir to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with Retrovir should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Use with Interferon- and Ribavirin-based Regimens in HIV-1/HCV Co-infected Patients

In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as zidovudine. Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with zidovudine in HIV-1/HCV co-infected subjects [see Clinical Pharmacology (12.3)], exacerbation of anemia due to ribavirin has been reported when zidovudine is part of the HIV regimen. Coadministration of ribavirin and zidovudine is not advised. Consideration should be given to replacing zidovudine in established combination HIV-1/HCV therapy, especially in patients with a known history of zidovudine-induced anemia.

Hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiRetroviral therapy for HIV-1 and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and zidovudine should be closely monitored for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia.

Discontinuation of zidovudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon alfa, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6) (see the complete prescribing information for interferon and ribavirin).
Use with Other Zidovudine-containing Products

Retrovir should not be administered with combinati