Introduction
Zidovudine (also known as AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) that was the first antiretroviral medication approved by the FDA for the treatment of HIV infection in 1987. It remains a fundamental component of many antiretroviral regimens and is also used for prevention of maternal-fetal HIV transmission.
Mechanism of Action
Zidovudine is a thymidine analogue that undergoes intracellular phosphorylation to its active metabolite, zidovudine triphosphate. This active form competes with endogenous thymidine triphosphate for incorporation into viral DNA by HIV reverse transcriptase. When incorporated, zidovudine triphosphate causes chain termination due to the absence of a 3'-hydroxyl group, thereby inhibiting viral replication.
Indications
- Treatment of HIV-1 infection in combination with other antiretroviral agents
- Prevention of maternal-fetal HIV transmission
- Post-exposure prophylaxis following occupational exposure to HIV-containing materials
Dosage and Administration
Adults: 300 mg twice daily or 200 mg three times daily Children: 160 mg/m² every 8 hours (maximum 200 mg every 8 hours) Renal impairment: Dose adjustment required for CrCl <15 mL/min Hepatic impairment: Reduce dose in significant hepatic impairment Route: Oral tablets, capsules, or syrup; IV infusion (for hospitalized patients)Pharmacokinetics
Absorption: Rapidly absorbed with 60-70% bioavailability Distribution: Widely distributed, crosses blood-brain barrier (CSF:serum ratio 0.6) Metabolism: Hepatic glucuronidation to inactive metabolite (GZDV) Elimination: Renal excretion (60-80% as metabolites), half-life 1-1.5 hours Protein binding: 25-38%Contraindications
- Life-threatening hypersensitivity to zidovudine or any component of the formulation
- Concomitant use with stavudine (due to antagonistic effects)
Warnings and Precautions
- Hematologic toxicity: Anemia, neutropenia, and thrombocytopenia may occur
- Myopathy: Myositis with elevated CPK levels reported with prolonged use
- Lactic acidosis: Potentially fatal complication, especially in women and obese patients
- Hepatic steatosis: Severe hepatomegaly with steatosis reported
- Immune reconstitution syndrome: May occur after initiation of antiretroviral therapy
- Lipoatrophy: Associated with long-term use of NRTIs
Drug Interactions
- Ganciclovir/valganciclovir: Increased risk of hematologic toxicity
- Ribavirin: Antagonistic antiviral activity against HIV
- Other bone marrow suppressive agents: Additive myelosuppression
- Probenecid: May decrease zidovudine clearance
- Stavudine: Pharmacologic antagonism, contraindicated
Adverse Effects
Common (>10%): Headache, nausea, vomiting, insomnia, asthenia Less common (1-10%): Anemia, neutropenia, dizziness, diarrhea, fever Serious (<1%): Lactic acidosis, severe hepatomegaly with steatosis, myopathy, pancytopenia, hypersensitivity reactionsMonitoring Parameters
- Baseline: CBC with differential, renal and hepatic function tests
- During therapy: CBC every 4-6 weeks, LFTs periodically
- Clinical monitoring: Signs of anemia, infection, myopathy, lactic acidosis
- Virologic monitoring: HIV RNA levels and CD4+ cell counts
- Therapeutic drug monitoring: Not routinely required
Patient Education
- Take exactly as prescribed; do not miss doses
- Report signs of anemia (fatigue, pale skin), infection (fever, sore throat), or muscle pain
- Notify all healthcare providers of zidovudine use
- Use effective contraception; discuss pregnancy planning with provider
- Do not breastfeed while taking zidovudine
- Store medication properly and check expiration dates
- Understand that zidovudine is not a cure for HIV
References
1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. 2. Zidovudine prescribing information. FDA-approved label. 3. Yarchoan R, et al. Administration of 3'-azido-3'-deoxythymidine, an inhibitor of HTLV-III/LAV replication, to patients with AIDS or AIDS-related complex. Lancet. 1986;1(8481):575-80. 4. Connor EM, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Engl J Med. 1994;331(18):1173-80. 5. Hawkins T, et al. Pharmacokinetics and bioavailability of oral zidovudine in patients with human immunodeficiency virus infection and hepatic disease. Antimicrob Agents Chemother. 1995;39(12):2731-4. 6. McLeod GX, et al. The long-term outcomes of zidovudine therapy in HIV-infected individuals. Ann Intern Med. 1998;129(6):470-8.