EPIVIR-HBV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EPIVIR-HBV (EPIVIR-HBV).
Lamivudine is a nucleoside analog that inhibits hepatitis B virus (HBV) DNA polymerase by competing with natural substrates and causing chain termination after incorporation into viral DNA.
| Metabolism | Lamivudine is primarily metabolized by endogenous phosphorylation to its active triphosphate metabolite. Minor hepatic metabolism via oxidation to trans-sulfoxide metabolite. Renal excretion of unchanged drug is the main route of elimination. |
| Excretion | Renal excretion of unchanged drug (~70%) via glomerular filtration and active tubular secretion; biliary/fecal elimination accounts for <10%. |
| Half-life | Terminal elimination half-life: 5-7 hours in adults; in renal impairment, half-life may extend to 20+ hours, requiring dose adjustment. |
| Protein binding | <36% bound to plasma proteins (primarily albumin) in vitro. |
| Volume of Distribution | 1.3 L/kg; indicates extensive distribution into total body water and tissues, including into cells. |
| Bioavailability | Oral: 86% (range 80-100%); food delays absorption but does not reduce extent. |
| Onset of Action | Oral: Time to peak plasma concentration 0.5-1.5 hours; antiviral effect begins within days, but clinical suppression of HBV DNA is evident after 2-4 weeks. |
| Duration of Action | Duration of antiviral effect: 24 hours, allowing once-daily dosing; continuous therapy required to maintain HBV suppression. |
| Molecular Weight | 229.26 Da |
100 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | For creatinine clearance 30-49 mL/min: 100 mg first dose, then 50 mg once daily; 15-29 mL/min: 100 mg first dose, then 25 mg once daily; 5-14 mL/min: 35 mg first dose, then 15 mg once daily; <5 mL/min: 35 mg first dose, then 10 mg once daily. |
| Liver impairment | No dosage adjustment required for Child-Pugh Class A, B, or C; pharmacokinetics not significantly altered in hepatic impairment. |
| Pediatric use | Approved for ages ≥2 years; dose based on weight: 10-14 kg: 15 mg once daily; 14-20 kg: 20 mg once daily; 20-30 kg: 30 mg once daily; ≥30 kg: 100 mg once daily. |
| Geriatric use | Dose selection based on renal function due to age-related decline in creatinine clearance; use renal adjustment guidelines. |
| 1st trimester | Limited human data, but animal studies show no evidence of teratogenicity. Use only if clearly needed. |
| 2nd trimester | No known risks in human pregnancy; consider use if benefit outweighs risk. |
| 3rd trimester | No known risks in human pregnancy; consider use if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for EPIVIR-HBV (EPIVIR-HBV).
| Placental transfer | Lamivudine crosses the placenta readily; detectable in cord blood at concentrations similar to maternal plasma. |
| Breastfeeding | Lamivudine is excreted into breast milk at low concentrations. The risk to the nursing infant is considered minimal, but caution is advised. Monitor infant for adverse effects. |
| Lactation Rating |
■ FDA Black Box Warning
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. Epivir-HBV is not approved for the treatment of HIV infection and should not be used in HIV-infected patients due to risk of HIV resistance.
| Serious Effects |
Hypersensitivity to lamivudine or any component of the formulation
| Precautions | Lactic acidosis and severe hepatomegaly with steatosis, Exacerbation of hepatitis B after discontinuation of therapy, Risk of HIV resistance in unrecognized HIV infection, Pancreatitis (especially in children), Renal impairment requires dose adjustment |
| Food/Dietary | No significant food interactions. May be taken with or without food. |
Loading safety data…
| L2 (Safer) |
| Teratogenic Risk | Category C. First trimester: No evidence of increased risk of major malformations based on limited human data; animal studies showed embryo-fetal toxicity at doses 35 times human exposure. Second and third trimesters: Reverse transcriptase inhibitors have been associated with lactic acidosis and hepatic steatosis in pregnant women; no specific teratogenic effects reported. |
| Fetal Monitoring | Monitor liver function tests, serum lactate, viral load, and CD4+ count. Perform ultrasound for fetal growth and anatomy if used during pregnancy. Observe for signs of lactic acidosis or hepatic steatosis in the mother. |
| Fertility Effects | No evidence of impaired fertility in animal studies at doses up to 130 mg/kg/day. Human data insufficient to establish effects on fertility. |
| Clinical Pearls | EPIVIR-HBV (lamivudine) is indicated for chronic hepatitis B. Monitor for hepatitis flares upon discontinuation; consider antiviral resistance (YMDD mutations) after prolonged use. Dose adjustment required for renal impairment (CrCl <50 mL/min). Not effective for HIV unless used with other antiretrovirals. |
| Patient Advice | Take exactly as prescribed; do not stop without consulting your doctor. · Report any signs of liver inflammation (jaundice, dark urine, abdominal pain). · Use a barrier contraceptive if you have HIV/HBV coinfection to prevent HIV transmission. · Do not double a missed dose; skip if close to next dose. · Inform all healthcare providers of your HBV status and lamivudine use. |