Lamidin

Approved Indication:

• Chronic Hepatitis B Virus (HBV) Infection
  Lamivudine is indicated for the treatment of chronic HBV infection in adults and pediatric patients (aged ≥2 years) who have evidence of HBV replication and active liver inflammation, as shown by elevated ALT levels or histologic evidence of necroinflammation or fibrosis.

Clinically Accepted Off-Label Use:

• HBV Prophylaxis During Immunosuppressive Therapy
  Used to prevent HBV reactivation in HBsAg-positive or anti-HBc–positive patients undergoing chemotherapy, immunosuppressive therapy, or organ transplantation.

Route of Administration: Oral (tablet or solution)

Adults – Chronic Hepatitis B:

• 100 mg orally once daily
• Duration: Minimum 12 months; longer if HBeAg-negative or until HBeAg seroconversion with sustained suppression

Pediatrics (2 to 17 years):

• 3 mg/kg orally once daily, up to a maximum of 100 mg/day

Elderly:

• Use with caution; assess renal function before initiating

Renal Impairment (Adults):
Dose adjustment based on creatinine clearance (CrCl):

• CrCl 30–49 mL/min: 50 mg once daily
• CrCl 15–29 mL/min: 25 mg once daily
• CrCl 5–14 mL/min: 15 mg once daily
• CrCl <5 mL/min or on dialysis: 10 mg once daily

Hepatic Impairment:

• No dose adjustment necessary

Lamivudine is a synthetic nucleoside analog of cytidine. It is phosphorylated intracellularly to its active triphosphate form, which competitively inhibits HBV DNA polymerase (reverse transcriptase). By incorporating into the viral DNA, lamivudine terminates the DNA chain, thereby preventing viral replication. This leads to a reduction in HBV DNA levels, improvement in liver function, and histological improvement of the liver over time.

• Absorption: Rapid and nearly complete oral absorption; bioavailability ~85%
• Distribution: Widely distributed in body tissues and fluids; volume of distribution ~1.3 L/kg
• Protein Binding: <36%
• Metabolism: Minimal hepatic metabolism; primarily metabolized via intracellular phosphorylation
• Elimination: Excreted unchanged in urine via renal filtration and active tubular secretion (~70%)
• Half-life:
  – Plasma: 5 to 7 hours
  – Intracellular (active form): 10 to 15 hours
• Time to Peak Concentration (Tmax): 0.5 to 1.5 hours
• Onset of Action: Virologic response observed within 12 to 24 weeks

Pregnancy:

• Former FDA Category C
• Use is generally considered safe in pregnancy when clinically indicated
• Often used in the third trimester in pregnant women with high viral loads to reduce vertical transmission

Lactation:

• Lamivudine is excreted in breast milk
• Considered safe during breastfeeding; no significant adverse effects reported in breastfed infants

Caution:

• Monitor hepatic function closely postpartum
• Use the lowest effective dose in pregnancy and lactation

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

• Hypersensitivity to lamivudine or any of its excipients
• Co-administration with other lamivudine- or emtricitabine-containing products
• Documented lamivudine resistance (in the context of HBV treatment)

• Hepatitis B Exacerbation Upon Discontinuation:
  Severe acute exacerbations of hepatitis B may occur after stopping lamivudine. Monitor liver function closely during and after discontinuation.
• Resistance Development:
  Long-term use increases the risk of resistant HBV strains, particularly with the YMDD mutation.
• Lactic Acidosis and Hepatic Steatosis:
  Rare, potentially fatal events have been reported, especially in obese females or those on prolonged therapy.
• Pancreatitis:
  Rare in pediatric patients; discontinue immediately if clinical signs arise.
• HIV Co-infection:
  Using lamivudine monotherapy in patients co-infected with HIV and HBV may lead to HIV resistance. Use HIV-appropriate dosing if HIV is present or suspected.

Common Adverse Effects:

• Headache
• Fatigue
• Nausea
• Diarrhea
• Abdominal discomfort
• Cough
• Musculoskeletal pain

Less Common:

• ALT flares after drug discontinuation
• Insomnia
• Rash
• Nasopharyngitis

Serious or Rare Side Effects:

• Lactic acidosis
• Hepatomegaly with steatosis
• Pancreatitis (especially in children)
• Virologic breakthrough due to resistance

Timing & Severity:

• Most adverse effects are mild to moderate and occur within the first few weeks
• Severe reactions are rare but may occur with prolonged use

• Avoid with Emtricitabine or Other Lamivudine Products:
  Risk of additive toxicity and no added benefit
• Trimethoprim/Sulfamethoxazole (TMP/SMX):
  May increase lamivudine exposure; no dose adjustment typically needed
• Nephrotoxic Agents:
  Use cautiously with drugs affecting renal function to prevent accumulation
• CYP450 Enzymes:
  Lamivudine is not a substrate, inhibitor, or inducer of CYP450 enzymes

• AASLD Guidelines:
  Lamivudine is no longer recommended as first-line monotherapy for HBV due to high resistance rates. It may still be considered where tenofovir or entecavir is unavailable or contraindicated.
• WHO Guidelines:
  Considered acceptable for use in HBV-infected pregnant women, especially in low-resource settings
• Prophylaxis in Chemotherapy:
  Lamivudine remains a standard option to prevent HBV reactivation during immunosuppressive therapy

• Temperature: Store below 25°C
• Humidity: Keep in a dry place
• Light Protection: Store in the original container to protect from light
• Handling Instructions:
  – Oral solution: Do not freeze; shake well before use
  – Use within the manufacturer’s recommended period after opening