Lamivudine + Zidovudine

Approved Indications:

• Treatment of HIV-1 Infection (Adults and Pediatric Patients ≥30 kg):
  Lamivudine + Zidovudine is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

Clinically Accepted Off-label Uses:

• Post-Exposure Prophylaxis (PEP):
  Used as part of a three-drug regimen for occupational and non-occupational exposure to HIV.
• Prevention of Mother-to-Child Transmission:
  Used in antenatal and intrapartum care as part of combination therapy to reduce vertical transmission of HIV.

Adults and Adolescents (≥30 kg):

• One tablet (150 mg Lamivudine + 300 mg Zidovudine) orally twice daily

Pediatrics (<30 kg):

• Use individual oral solutions or tablets to calculate weight-based dosing:
• Lamivudine: 4 mg/kg twice daily
• Zidovudine: 180–240 mg/m² every 12 hours (up to 300 mg twice daily)

Renal Impairment:

• Lamivudine requires dose adjustment if CrCl <50 mL/min
• Use individual components to adjust dose appropriately

Hepatic Impairment:

• Use with caution; Zidovudine may accumulate in hepatic impairment. Monitor hepatic function and blood counts.

Elderly:

• Caution advised; assess renal and hepatic function prior to initiation

Lamivudine and Zidovudine are both nucleoside reverse transcriptase inhibitors (NRTIs). After phosphorylation to their active triphosphate forms, they competitively inhibit reverse transcriptase, an HIV enzyme essential for viral RNA conversion to DNA. Incorporation into viral DNA results in chain termination and prevents further viral replication. The combination provides a synergistic effect and reduces the emergence of resistance.

Lamivudine:

• Bioavailability: ~85%
• Plasma Half-life: 5–7 hours
• Intracellular Half-life (active form): ~10–15 hours
• Metabolism: Minimal hepatic metabolism
• Excretion: ~70% unchanged via urine

Zidovudine:

• Bioavailability: ~60–70%
• Plasma Half-life: ~1 hour
• Intracellular Half-life: ~3–4 hours
• Metabolism: Hepatic glucuronidation to inactive metabolite
• Excretion: Renal (~60–70% as metabolite)

Onset of Action: Within hours of initial dosing
Steady-state concentration: Achieved within 2–3 days

Pregnancy:

• Former FDA Category C (both drugs)
• Widely used during pregnancy; effective in preventing perinatal transmission of HIV. No major teratogenic risks identified.

Lactation:

• Both drugs are excreted in breast milk
• Breastfeeding not recommended in high-resource settings; may be permitted under strict ART coverage in low-resource settings
• Monitor infant for hematologic toxicity

• Primary Class: Antiretroviral Agent
• Subclass: Nucleoside Reverse Transcriptase Inhibitor (NRTI) Combination

• Known hypersensitivity to lamivudine, zidovudine, or any excipient in the formulation
• Significant hematologic toxicity (e.g., anemia, neutropenia)
• Concomitant use with other lamivudine- or zidovudine-containing products
• Severe hepatic impairment (relative contraindication due to zidovudine component)

• Lactic Acidosis & Hepatic Steatosis:
  Risk is higher in females, obese patients, and prolonged therapy. Discontinue if suspected.
• Hematologic Toxicity (Zidovudine):
  Risk of anemia and neutropenia; monitor CBC regularly, especially in advanced HIV
• Myopathy (Zidovudine):
  Associated with long-term use; presents with muscle weakness and elevated CK
• Immune Reconstitution Syndrome:
  May occur after initiating ART; monitor for inflammatory symptoms
• Pancreatitis (Lamivudine):
  Rare, mostly in pediatric patients. Discontinue if suspected.
• HBV Reactivation:
  Abrupt discontinuation of lamivudine in HBV/HIV co-infection can cause hepatic flares

Common Adverse Effects (≥1%):

• Headache
• Nausea
• Vomiting
• Diarrhea
• Fatigue
• Abdominal pain
• Myalgia
• Fever
• Insomnia

Serious and Rare Adverse Effects:

• Severe anemia or neutropenia
• Lactic acidosis
• Hepatic steatosis
• Myopathy
• Pancreatitis
• Hypersensitivity reactions
• Seizures (rare)

Timing & Severity:

• Hematologic toxicity may appear within weeks
• Myopathy and hepatic complications typically occur with prolonged use
• Gastrointestinal and CNS symptoms are usually mild and transient

Major Drug-Drug Interactions:

• Stavudine: Antagonistic effect with zidovudine
• Ribavirin: Increases hematologic toxicity
• Nephrotoxic agents: Can impair lamivudine excretion

Other Considerations:

• Zidovudine metabolism may be inhibited by probenecid and other glucuronidation inhibitors
• Lamivudine has no significant CYP450 involvement

• WHO and DHHS Guidelines (2024–2025):
  Lamivudine + Zidovudine remains an alternative option when Tenofovir cannot be used
  Recommended in pregnancy and post-exposure prophylaxis (PEP)
• New Safety Monitoring Updates:
  Enhanced hematologic monitoring is advised in elderly and those with baseline anemia
  Continued emphasis on lactic acidosis risk in NRTI-based combinations

• Temperature: Store below 25°C (77°F)
• Humidity: Store in a dry place
• Light Sensitivity: Keep in original packaging, protect from light
• Handling:
  – Do not freeze liquid formulations
  – No shaking or reconstitution needed for tablets
  – Keep tightly closed when not in use