Lamivudine [For HIV Infection]

Approved Indications:

• HIV-1 Infection (Adults and Pediatrics):
  Lamivudine is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients aged 3 months and older.

Clinically Accepted Off-label Uses:

• HIV-2 Infection (in combination):
  Used off-label in combination antiretroviral regimens for HIV-2 infection.
• Perinatal HIV Transmission Prevention:
  Used in antiretroviral regimens during pregnancy to reduce the risk of mother-to-child HIV transmission.

Route of Administration: Oral

Adults and Adolescents (≥25 kg):

• 300 mg orally once daily
  or
• 150 mg orally twice daily in divided doses

Pediatric Patients (3 months to <25 kg):

• 3 mg/kg orally twice daily (maximum 150 mg per dose)
  or
• 8 mg/kg orally once daily (maximum 300 mg/day)

Renal Impairment (Adults):
Adjust based on creatinine clearance (CrCl):

• CrCl 30–49 mL/min: 150 mg once daily
• CrCl 15–29 mL/min: 150 mg first dose, then 100 mg once daily
• CrCl 5–14 mL/min: 150 mg first dose, then 50 mg once daily
• CrCl <5 mL/min: 50 mg first dose, then 25 mg once daily

Hepatic Impairment:

• No dose adjustment is required

Geriatric Patients:

• Use with caution and assess renal function before and during treatment

Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI). It is phosphorylated intracellularly to its active form, lamivudine triphosphate, which inhibits HIV reverse transcriptase by competing with the natural substrate, deoxycytidine triphosphate. Once incorporated into the viral DNA, it causes premature DNA chain termination, thereby halting viral replication and decreasing the viral load in the body.

• Absorption: Rapid and extensive oral absorption; bioavailability approximately 85%
• Distribution: Wide distribution, including cerebrospinal fluid; volume of distribution ~1.3 L/kg
• Protein Binding: <36%
• Metabolism: Minimal hepatic metabolism
• Elimination: Primarily excreted unchanged in urine via active tubular secretion (~70%)
• Half-life:
  – Plasma: 5–7 hours
  – Intracellular (active form): 10–15 hours
• Tmax (Time to Peak Concentration): 0.5 to 1.5 hours
• Steady-State Concentration: Achieved within 2 days

Pregnancy:

• Former FDA Category C
• Widely used in pregnancy as part of combination antiretroviral therapy (ART); no significant increase in birth defects reported

Lactation:

• Lamivudine is excreted into breast milk
• Generally considered safe for breastfeeding in resource-limited settings when maternal ART is continued
• Monitor infants for potential adverse effects (e.g., hematologic toxicity)

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

• Known hypersensitivity to lamivudine or any component of the formulation
• Co-administration with other lamivudine-containing products (e.g., Epivir-HBV)
• Concurrent use with emtricitabine-containing products due to similarity and risk of toxicity

• Lactic Acidosis and Severe Hepatomegaly with Steatosis:
  Rare but potentially fatal, especially in females, obese patients, or those on prolonged therapy
• HBV Co-infection:
  Discontinuation may result in severe acute exacerbation of hepatitis B; monitor hepatic function closely
• Pancreatitis:
  Cases reported, particularly in pediatric patients; discontinue if suspected
• Emergence of Drug Resistance:
  Rapid resistance may occur with inadequate therapy or monotherapy
• Hematologic Toxicity:
  Anemia, neutropenia, and thrombocytopenia may occur, especially with concomitant zidovudine
• Immune Reconstitution Syndrome:
  May unmask opportunistic infections after initiation of ART

Common Adverse Effects (≥1%):

• Headache
• Fatigue
• Nausea
• Diarrhea
• Nasal symptoms
• Cough
• Abdominal discomfort

Less Common Adverse Effects:

• Rash
• Insomnia
• Myalgia
• Fever
• Vomiting

Serious Adverse Effects (Rare):

• Lactic acidosis
• Severe hepatomegaly with steatosis
• Pancreatitis
• Severe neutropenia or anemia
• Hypersensitivity reactions

Timing and Severity:

• Most side effects are mild to moderate and appear within the first few weeks
• Serious adverse reactions typically occur with long-term or inappropriate use

Avoid Co-administration With:

• Emtricitabine or other lamivudine-containing drugs: Increases risk of toxicity without added efficacy
• Zalcitabine: Antagonistic effect on HIV replication

Use with Caution With:

• Trimethoprim/Sulfamethoxazole (TMP-SMX): May increase lamivudine plasma levels
• Nephrotoxic agents: Potential accumulation due to renal clearance

CYP450 Interactions:

• Lamivudine does not inhibit or induce cytochrome P450 enzymes and is not metabolized by them

• DHHS and WHO Guidelines (2024–2025):
  Lamivudine remains part of preferred first-line regimens (e.g., tenofovir + lamivudine + dolutegravir)
  Also included in second-line and pregnancy-specific regimens
• Pregnancy and Breastfeeding Guidance:
  Recommended as part of maternal ART to prevent perinatal HIV transmission
• HBV/HIV Co-infection:
  Lamivudine must be used with a second anti-HBV agent such as tenofovir to prevent resistance

• Storage Temperature: Below 25°C (77°F)
• Humidity: Store in a dry place; keep container tightly closed
• Light Sensitivity: Protect from direct light
• Oral Solution:
  – Do not freeze
  – Shake well before use
  – Follow manufacturer’s guidance for expiry after opening (typically 30 days)