RETROVIR

What it is

RETROVIR is the brand name for zidovudine, an antiretroviral drug active against human immunodeficiency virus (HIV). Zidovudine is an inhibitor of the in vitro replication of some retroviruses including HIV and is a thymidine analogue in which the 3'-hydroxy group is replaced by an azido group. RETROVIR is available as capsules containing 100 mg or 250 mg of zidovudine, and as a syrup in which each 5 mL contains 50 mg zidovudine.

Approved indications

— Treatment of HIV infection, alone and in combination with other antiretroviral therapies.

Dosing overview

A broad range of dosage regimens has been employed; a daily dose of 500–600 mg in two to five divided doses has been used commonly worldwide for adults weighing at least 30 kg. Significant anaemia (haemoglobin of less than 7.5 g/dL or reduction of more than 25% of baseline) and/or significant granulocytopenia (granulocyte count of less than 750/mm³ or reduction of more than 50% from baseline) require a dose interruption until evidence of marrow recovery is observed. For less severe anaemia or granulocytopenia, a reduction in daily dose may be adequate.

Key safety warnings

Therapy with RETROVIR is commonly associated with haematologic toxicity including granulocytopenia and severe anaemia requiring transfusions particularly in patients with advanced HIV disease. Frequent blood counts are strongly recommended in patients with advanced HIV disease taking zidovudine, with monitoring at least every 2 weeks. Treatment with zidovudine has been associated with loss of subcutaneous fat, with the incidence and severity related to cumulative exposure, most evident in the face, limbs and buttocks, and may be only partially reversible with improvement taking several months when switching to a zidovudine-free regimen. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of antiretroviral nucleoside analogues either alone or in combination, including zidovudine. Clinical features which may be indicative of the development of lactic acidosis include generalised weakness, anorexia, and sudden unexplained weight loss, gastrointestinal symptoms and respiratory symptoms. Sensitisation reactions, including anaphylaxis in one patient, have been reported in individuals receiving zidovudine therapy.

Contraindications

RETROVIR preparations are contraindicated for patients who have potentially life-threatening allergic reactions to any of the components of the formulation. RETROVIR should not be given to patients with abnormally low neutrophil counts (less than 0.75 × 10⁹/L) or abnormally low haemoglobin levels (less than 7.5 g/dL or 4.65 mmol/L).

PBS listing

RETROVIR capsules 100 mg and 250 mg are each listed on the PBS with streamlined restriction and an ex-manufacturer price of A$129.81, with the syrup formulation (10 mg per mL, 200 mL) also listed with streamlined restriction at an ex-manufacturer price of A$36.46.

Regulatory history

RETROVIR syrup was first listed on the ARTG on 11 December 1992, whilst the 100 mg and 250 mg capsule formulations were first listed on 1 March 2011.