Drug Detail

Zidovudine

Last Updated June 10, 2016

Trade Names

  • Zidovudine: Retrovir, Adco-Zidovudine, Aspen Zidovudine, Cipla-Zidovudine, Sonke Zidovudine, Zidomat (Mylan), Dozra, Pharma-Q Zidovudine;
  • Lamivudine/zidovudine: Combivir, Aspen Lamzid, Adco-Lamivudine + Zidovudine, Cipla-Duovir, Divuwin, Lodiz, Sonke Lamivudine+Zidovudine, Zovilam;
  • Lamivudine/abacavir/zidovudine: Trizivar, Sonke Abaclamizid;
  • Lamivudine/zidovudine with efavirenz: Cipla-Duovir/Cipla Efavirenz copack;
  • Zidovudine/lamivudine/nevirapine: Mivirdo (Mylan), Triplavar

Drug Classification

Nucleoside reverse transcriptase inhibitor antiretroviral

Formulations

  • Zidovudine: 100 mg, 250 mg capsules; 100 mg, 300 mg tablets; oral solution 50 mg/5 mL; syrup 50 mg/5 mL; intravenous infusion 200 mg/20 mL;
  • Lamivudine/zidovudine: 150/300 mg tablets;
  • Lamivudine/abacavir/zidovudine: 150/300/300 mg tablet;
  • Lamivudine/zidovudine with Efavirenz: 150/300 mg tablets copackaged with efavirenz 600 mg tablets;
  • Zidovudine/lamivudine/nevirapine: 300/150/200 mg tablet

Indications and Pharmacology

Indication: treatment of HIV infection in combination with other antiretrovirals, reduction of perinatal transmission of HIV, postexposure prophylaxis in combination with other antiretrovirals.

Mechanism of action*: a thymidine analogue that is phosphorylated intracellularly to zidovudine 5’-triphosphate which interferes with HIV viral RNA–dependent DNA polymerase inhibiting viral replication.

Pharmacokinetics: metabolized in the liver via glucuronidation to inactive metabolite GZDV; 65% to 75% of GZDV is excreted in the urine. Half-life: serum = 1.1 hours; intracellular = 7 hours. Good cerebrospinal fluid penetration.

Dosage

Adult Dose for Treatment of HIV:

  • 250-300 mg twice daily; dose may be reduced to 200 mg twice daily if needed for haematologic toxicity.
  • Intravenous infusion over 1 hour, 1-2 mg/kg 4 hourly, in 5% glucose to give zidovudine concentration 2 or 4 mg/mL (only until oral therapy can be given).

Adult Dose for Prevention of Mother-to-Child Transmission:

  • 300 mg twice daily from Week 14 of pregnancy.
  • 300 mg every 3 hours from onset of labour to delivery.

Take without regard to meals.*

Use in Renal or Hepatic Insufficiency: Decrease dose by 50% or double dosage interval if significant liver disease.

Dosage for patients with chronic kidney disease or end-stage renal disease:

  • Creatinine clearance ≥ 15 mL/min: no adjustment.
  • Creatinine clearance < 15 mL/min: 100 mg orally every 6-8 hours.
  • Receiving haemodialysis: 100 mg orally every 6-8 hours.
  • Receiving peritoneal dialysis: 100 mg orally every 6-8 hours.
  • Zidovudine/lamivudine should be administered as separate component medications in patients with creatinine clearance < 50 mL/min.

Use in Pregnancy and Breastfeeding: Category C. Excreted in breast milk.*

Use in Children:

Prevention of mother-to-child HIV transmission (in neonates): Note: start as soon as possible after birth, preferably within 6-12 hours of delivery. Continue dose from birth through 6 weeks of age.

Oral:

  • Full-term infants: 4 mg/kg every 12 hours.
  • Premature infants
    • ≥ 30-35 weeks: 2 mg/kg every 12 hours for 2 weeks, then 3 mg/kg every 12 hours
    • < 30 weeks: 2 mg/kg every 12 hours for 4 weeks, then 3 mg/kg every 12 hours

Intravenous (infants unable to receive oral dosing):

  • Full-term infants: 3 mg/kg every 12 hours
  • Premature infants
    • ≥ 30-35 weeks: 1.5 mg/kg every 12 hours for 2 weeks, then 2.3 mg/kg every 12 hours
    • < 30 weeks: 1.5 mg/kg every 12 hours for 4 weeks, then 2.3 mg/kg every 12 hours

Paediatric dose (3 months to 12 years): 180 mg/m2 twice daily orally (maximum: 800 mg/day) (suspension may be given with food).

Warnings

US Prescribing Information Boxed Warning*: haematologic toxicity including neutropenia and severe anaemia have been associated with zidovudine.

  • Full blood counts recommended at 1 month and 3 monthly thereafter.
  • Neutropenia and anaemia may be dose limiting. Dose should be reduced if neutrophil count is < 1.5 x 109/L and therapy stopped if count is < 1 x 109/L.
  • Anaemia usually occurs after 4-6 weeks of therapy. Dose should be reduced if haemoglobin is < 10 g/dL and discontinued if < 8 g/dL.

Oesophageal ulceration may occur unless adequate fluid is ingested with oral doses.

US Prescribing Information Boxed Warning*: symptomatic myopathy associated with prolonged use of zidovudine.

US Prescribing Information Boxed Warning*: lactic acidosis/hepatomegaly with steatosis has been reported with nucleoside analogues with fatal cases reported. Use in caution with patients with risk factors for liver disease and suspend treatment if a patient develops signs and symptoms.

Drug–Drug Interactions

Contraindicated: none.

Precautions: ganciclovir (potential for increased haematologic toxicity), ribavirin (inhibits phosphorylation of zidovudine and increased haematologic toxicity),* myelosuppressive agents (increased risk of bone marrow suppression), probenecid (delayed excretion), valproate (zidovudine levels significantly increased).

Considerations for Special Populations

See above for pregnancy and lactation.

Adverse Effects

Bone marrow suppression, nausea, vomiting, headache, insomnia, nail pigmentation, fat redistribution, myopathy.

*Information from US prescribing information.
Recommendation from Southern African HIV Clinician Society Guidelines.
Recommendation from South African Renal Society, 2008.