Zidovudine

Zidovudine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) — the first antiretroviral approved for HIV (1987). While largely replaced by newer agents for routine HIV treatment, it remains important for prevention of maternal-fetal HIV transmission (intrapartum IV dosing) and as a component of some neonatal prophylaxis regimens. It is also the only ARV available as an IV formulation.[1]

Administration

  • Type: Nucleoside reverse transcriptase inhibitor (NRTI)
  • Dosage Forms: 100 mg capsules; 300 mg tablets; 10 mg/mL oral solution (syrup); 10 mg/mL IV injection
  • Routes of Administration: Oral, intravenous
  • Common Trade Names: Retrovir; also in fixed-dose combinations: Combivir (zidovudine/lamivudine), Trizivir (zidovudine/lamivudine/abacavir)

Adult Dosing

  • HIV treatment: 300 mg PO twice daily (or 200 mg PO three times daily)[1]
  • IV dosing: 1 mg/kg IV infused over 1 hour, every 4 hours (~5–6 mg/kg/day) — use when oral not feasible[1]
  • Intrapartum (prevention of perinatal transmission):[1]
    • 2 mg/kg IV loading dose, then 1 mg/kg/hr continuous infusion until umbilical cord clamped
    • Scheduled cesarean: Begin IV 3 hours before surgery
    • Not required if mother is virologically suppressed (HIV RNA <50 copies/mL) and adherent to oral ART[2]
  • May take with or without food

Pediatric Dosing

  • Neonatal prophylaxis: Weight-based dosing starting within 6–12 hours of birth; typically 4 mg/kg PO BID (≥35 weeks gestational age) for 4–6 weeks[1]
  • Higher-risk neonates: Combined with nevirapine and/or lamivudine per current perinatal guidelines
  • HIV treatment (children ≥4 weeks): Weight-based or BSA-based dosing (e.g., 240 mg/m² PO BID); consult pediatric ID[1]

Special Populations

Pregnancy Rating

  • Formerly Category C; extensively studied in pregnancy[1]
  • Landmark ACTG 076 trial demonstrated reduced perinatal HIV transmission from 25% to 8% with zidovudine prophylaxis
  • Crosses the placenta; neonatal plasma concentrations approximate maternal levels at delivery[1]
  • Antiretroviral Pregnancy Registry: 1-800-258-4263

Lactation risk

  • Excreted in human milk; women with HIV should not breastfeed (risk of HIV transmission)[1]

Renal Dosing

  • Adult: CrCl <15 mL/min or on hemodialysis/peritoneal dialysis: 100 mg PO q6–8h (or 1 mg/kg IV q6–8h)[1]
    • Hemodialysis has negligible effect on zidovudine removal (but enhances removal of its glucuronide metabolite)
  • Pediatric: Insufficient specific data

Hepatic Dosing

  • Adult: Insufficient data to recommend dose adjustment; zidovudine is primarily hepatically metabolized, so concentrations may be increased. Frequent hematologic monitoring is advised[1]
  • Pediatric: Not studied

Contraindications

  • Allergy to class/drug
  • Potentially life-threatening hypersensitivity reactions reported (including anaphylaxis)
  • Do not combine with stavudine (d4T) — antagonistic antiviral interaction[1]

Adverse Reactions

Serious

  • Hematologic toxicity (the defining toxicity): Severe anemia, neutropenia, pancytopenia, aplastic anemia — risk increases with advanced HIV disease, prolonged use, and pre-existing bone marrow suppression[1]
  • Lactic acidosis with hepatic steatosis (NRTI class effect; including fatal cases) — presents with nausea, vomiting, abdominal pain, fatigue, dyspnea, elevated lactate[1]
  • Hepatotoxicity (including hepatic failure)
  • Myopathy/rhabdomyolysis with prolonged use (related to mitochondrial toxicity)[3]
  • Immune reconstitution inflammatory syndrome (IRIS)
  • Stevens-Johnson syndrome

Common

  • Headache, malaise, fatigue, nausea, vomiting, anorexia[1]
  • Macrocytosis (MCV elevation — nearly universal and can serve as an indirect marker of adherence)[3]
  • Insomnia
  • Nail pigmentation (bluish-brown discoloration)
  • Lipoatrophy (subcutaneous fat loss — NRTI class effect, particularly with thymidine analogs)

Pharmacology

  • Half-life: ~0.5–3 hours (plasma); intracellular triphosphate half-life ~3–4 hours[3]
  • Metabolism: Hepatic glucuronidation (UGT) to inactive GZDV metabolite (~74% of dose); minor renal excretion of unchanged drug (~14%)[3]
  • Excretion: ~14% unchanged in urine, ~74% as glucuronide metabolite in urine; remainder in feces[1]

Mechanism of Action

Zidovudine is a thymidine analog that is phosphorylated intracellularly to its active form, zidovudine triphosphate (ZDV-TP). ZDV-TP competes with natural thymidine triphosphate for incorporation into growing HIV DNA by reverse transcriptase. Once incorporated, it acts as a chain terminator because it lacks the 3'-hydroxyl group needed for DNA chain elongation, halting proviral DNA synthesis.[1] It has no clinically significant activity against HIV-2.[3]

Comments

  • ED role — intrapartum dosing: The most common reason an ED or L&D physician will encounter zidovudine is for IV intrapartum prophylaxis in an HIV+ woman presenting in labor. Know the loading dose (2 mg/kg IV) and infusion (1 mg/kg/hr). However, if the patient is on suppressive ART with an undetectable viral load and no adherence concerns, IV zidovudine is no longer required[2]
  • Hematologic monitoring pearl: If a patient on zidovudine presents with fatigue, pallor, dyspnea, or recurrent infections, check a CBC immediately — severe anemia (may require transfusion) and neutropenia are the dose-limiting toxicities. Dose reduction or discontinuation may be needed at Hgb <7.5 g/dL or ANC <750[1]
  • Macrocytosis as adherence marker: An elevated MCV (often >100 fL) is nearly universal on zidovudine and does not require workup. Conversely, a normal MCV in a patient supposedly taking zidovudine may suggest non-adherence[3]
  • Lactic acidosis: NRTI class effect. Suspect in patients with unexplained nausea, vomiting, abdominal pain, dyspnea, fatigue, and elevated lactate/anion gap. Discontinue zidovudine immediately and provide supportive care[1]
  • Drug interactions: Avoid combining with stavudine (antagonistic), doxorubicin (antagonistic), and ribavirin (worsens anemia). Trimethoprim and probenecid increase zidovudine levels; use caution with other myelosuppressive agents (ganciclovir, TMP-SMX, dapsone)[1]
  • Overdose: Exposures up to 50 grams reported; symptoms include fatigue, headache, vomiting, and hematologic disturbances. No specific antidote; supportive care. Hemodialysis does not effectively remove zidovudine but enhances clearance of its metabolite[1]

See Also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 Retrovir (zidovudine) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2020.
  2. ↑ 2.0 2.1 Retrovir (zidovudine). Medscape Drug Reference. Accessed 2025.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Zidovudine. StatPearls. NCBI Bookshelf. Updated 2023.
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