Zidovudine is converted intracellularly to zidovudine triphosphate, which inhibits replication of retroviruses, including HIV, by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).

Zidovudine, a nucleoside reverse transcriptase inhibitor, is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Prevention Of Maternal-Fetal HIV-1 Transmission Zidovudine is indicated for the prevention of maternal-fetal HIV-1 transmission. The indication is based on a dosing regimen that included 3 components:

• Antepartum therapy of HIV-1–infected mothers
• Intrapartum therapy of HIV-1–infected mothers
• Post-partum therapy of HIV-1–exposed neonate

Points to consider prior to initiatingZidovudine in pregnant women for the prevention of maternal-fetal HIV-1 transmission include:

• In most cases,Zidovudine for prevention of maternal-fetal HIV-1 transmission should be given in combination with other antiretroviral drugs.
• Prevention of HIV-1 transmission in women who have receivedZidovudine for a prolonged period before pregnancy has not been evaluated.
• Because the fetus is most susceptible to the potential teratogenic effects of drugs during the first 10 weeks of gestation and the risks of therapy withZidovudine during that period are not fully known, women in the first trimester of pregnancy who do not require immediate initiation of antiretroviral therapy for their own health may consider delaying use; this indication is based on use after 14 weeks’ gestation.

Prophylaxis of HIV infection in neonates:

• Child: 2 mg/kg 6 hrly, starting within 12 hr after birth and continuing for 6 wk.

HIV infection:

• Adult: 250 mg or 300 mg bid, in combination with other antiretroviral agents.
• Child: As soln: 4 to <9 kg: 12 mg/kg bid; 9 to <30 kg: 9 mg/kg bid; ≥30 kg: 250 mg or 300 mg bid. As cap/tab: 8-13 kg: 100 mg bid; 14-21 kg: 100 mg in the morning, 200 mg in the evening; 22-30 kg: 200 mg bid; ≥30 kg: 250 mg or 300 mg bid. Alternatively (based on BSA), 480 mg/m2 daily in 2-3 divided doses. Doses are given in combination with other antiretroviral agents.

Prophylaxis of maternal-fetal HIV transmission:

• Adult: 100 mg 5 times daily, starting on the 14th wk of gestation until the start of labour.

Administration

May be taken with or without food.

Hypersensitivity; abnormally low neutrophil counts (<0.75 x 109/L) or Hb levels (<7.5 g/dL or 4.65 mmol/L); newborn infants with hyperbilirubinaemia requiring treatment other than phototherapy, or with increased transaminase levels >5 times the ULN. Lactation. Concomitant use with interferon alfa (with or witho ribavirin) in HIV and hepatitis B or C virus co-infected patients.

Dizziness, headache, malaise, myalgia, GI symptoms (e.g. abdominal pain, diarrhoea, nausea, vomiting), anorexia, immune reconstitution syndrome, lipodystrophy, metabolic abnormalities, mitochondrial dysfunction, osteonecrosis; raised liver enzymes, creatine phosphokinase; hyperbilirubinaemia, myalgia, myositis. Rarely, aplastic anaemia, pure red cell aplasia, pancytopenia, thrombocytopenia, rhabdomyolysis, cardiomyopathy, convulsions, pancreatitis.

Overdose Effects

Symptoms: Vomiting, CNS effects (e.g. fatigue, dizziness, drowsiness, lethargy, confusion), haematologic effects (e.g. anaemia, decreased Hb). Bone marrow hypoplasia, mild ataxia, tonic-clonic seizure and increased serum concentration of AST and ALT may also occur.

Management: Supportive and symptomatic treatment. Induce emesis and admin activated charcoal to prevent further absorption of unrecovered drug.

Severe renal and hepatic impairment. Childn. Pregnancy.

Use in Special Populations

Renal Impairment:

• ESRD maintained on haemodialysis or peritoneal dialysis: 100 mg 6-8 hrly.
• CrCl <10-15 mL/min: 100 mg 6-8 hrly.

Hepatic Impairment: Dose reduction may be needed.

Pregnancy & Lactation

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.