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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EPIVIR-HBV (EPIVIR-HBV).
| Breastfeeding | Lamivudine is excreted into human breast milk at low concentrations (milk-to-plasma ratio 0.6–3.3). The relative infant dose is approximately 2–4% of maternal weight-adjusted dose. Caution is advised as safety in nursing infants has not been established. |
| 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. |
■ 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"] |
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| 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. |