LAMIVUDINE
Clinical safety rating: safe
Human studies have proved safety
Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits HIV reverse transcriptase and hepatitis B virus polymerase via incorporation into viral DNA, causing chain termination.
| Metabolism | Lamivudine is not significantly metabolized; it is primarily eliminated unchanged in urine via active renal secretion. Intracellularly, it is phosphorylated to its active triphosphate form. |
| Excretion | Renal: approximately 70% of the dose excreted unchanged in urine via glomerular filtration and active tubular secretion; biliary/fecal: minimal, less than 5% |
| Half-life | Terminal elimination half-life: 5-7 hours in adults; prolonged to 20-35 hours in patients with creatinine clearance <30 mL/min, necessitating dose adjustment |
| Protein binding | <36% bound to plasma proteins (primarily albumin) — low binding minimizes interactions |
| Volume of Distribution | 1.3 L/kg; distributes widely into total body water, including cerebrospinal fluid (CSF-to-plasma ratio ~0.6) |
| Bioavailability | Oral: 86% (range 80-92%); no significant food effect |
| Onset of Action | Oral: antiviral effect begins within 1-2 hours due to intracellular phosphorylation; maximal effect by 4-6 hours |
| Duration of Action | Duration: approximately 12 hours based on intracellular triphosphate half-life of 10-15 hours; dosing interval is 12-24 hours depending on indication |
| Molecular Weight | 229.26 |
150 mg orally twice daily or 300 mg orally once daily; for HIV-1 infection, 300 mg once daily or 150 mg twice daily; for hepatitis B, 100 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | CrCl >=50 mL/min: no adjustment; CrCl 30-49 mL/min: 150 mg once daily (HIV) or 100 mg once daily (HBV); CrCl 15-29 mL/min: 150 mg first dose then 100 mg once daily (HIV) or 100 mg first dose then 50 mg once daily (HBV); CrCl 5-14 mL/min: 150 mg first dose then 50 mg once daily (HIV) or 100 mg first dose then 25 mg once daily (HBV); CrCl <5 mL/min: 150 mg first dose then 25 mg once daily (HIV) or 100 mg first dose then 10 mg once daily (HBV). Dosing recommendations per FDA labeling. |
| Liver impairment | No dosage adjustment required in patients with mild to moderate hepatic impairment (Child-Pugh A or B). Safety and efficacy in severe hepatic impairment (Child-Pugh C) not established; use with caution. |
| Pediatric use | For HIV-1: age 3 months to 16 years, dose 4 mg/kg (max 150 mg) orally twice daily; for body weight >=14 kg, 4 mg/kg twice daily; for weight 30 kg or more, adult dose may be used. For hepatitis B: pediatric patients not indicated per FDA; off-label use in children with chronic HBV (age >2 years) at 3 mg/kg once daily (max 100 mg). |
| Geriatric use |
| 1st trimester | Use only if clearly needed; limited human data but animal studies show no teratogenicity at subtoxic doses. |
| 2nd trimester | Safe in pregnancy as part of antiretroviral therapy; no increased risk of birth defects per Antiretroviral Pregnancy Registry. |
| 3rd trimester | Safe; continued treatment recommended to prevent mother-to-child transmission. |
Clinical note
Trimethoprim/sulfamethoxazole increases lamivudine exposure Severe acute exacerbations of hepatitis B have been reported upon discontinuation.
| Placental transfer | Significant; lamivudine crosses the placenta with cord blood concentrations similar to maternal plasma (ratio ~1.0). |
| Breastfeeding | Lamivudine is excreted into breast milk in low concentrations (approximately 0.5% of maternal weight-adjusted dose). In HIV-infected mothers, breastfeeding is generally avoided in developed countries; in resource-limited settings, WHO recommends exclusive breastfeeding under antiretroviral therapy. |
■ FDA Black Box Warning
Posttreatment exacerbations of hepatitis B have been reported in patients who have discontinued lamivudine. Hepatic function should be monitored closely for at least several months in patients who discontinue anti-hepatitis B therapy.
| Common Effects | Hepatitis B |
| Serious Effects |
Hypersensitivity to lamivudine or any component
| Precautions | Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, Pancreatitis, particularly in pediatric patients with advanced HIV disease, Immune reconstitution syndrome, Hepatitis B exacerbation upon discontinuation, Risk of HIV resistance when used alone or with other NRTIs in HBV patients with unrecognized or untreated HIV |
| Food/Dietary | No significant food interactions. May be taken with or without food. Avoid excessive alcohol consumption as it may increase risk of hepatotoxicity. |
Loading safety data…
| No specific geriatric dose adjustments; use with caution due to age-related decline in renal function. Monitor renal function and adjust dose based on CrCl as per adult renal dosing. |
| Lactation Rating | L2 (Safe) |
| Teratogenic Risk | Lamivudine is FDA Pregnancy Category C. Human data show no increased risk of major birth defects in first trimester exposure based on Antiretroviral Pregnancy Registry. No evidence of fetal toxicity in second/third trimester. Animal studies showed embryotoxicity at high doses. |
| Fetal Monitoring | Monitor maternal CD4, viral load, liver function, renal function. Fetal ultrasound for growth assessment. Monitor infant for HIV status after birth. Monitor for maternal anemia and pancreatitis. |
| Fertility Effects | No adverse effects on fertility in animal studies. No human data suggest impairment of fertility. Antiretroviral therapy may improve fertility by controlling HIV. |
| Clinical Pearls | Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) used in HIV-1 and hepatitis B treatment. Monitor renal function as dose adjustment is required for CrCl <50 mL/min. Do not use as monotherapy for HIV due to rapid resistance. Hepatitis B flares may occur upon discontinuation; monitor LFTs. Lactic acidosis and severe hepatomegaly with steatosis reported, especially in women and obesity. |
| Patient Advice | Take exactly as prescribed; do not skip doses or stop without consulting provider. · Lamivudine does not cure HIV or hepatitis B, but reduces viral load and slows disease progression. · Use in combination with other antiretrovirals for HIV; never as monotherapy. · Report persistent nausea, abdominal pain, or unexplained fatigue (signs of lactic acidosis). · If discontinuing hepatitis B therapy, monitor liver function closely for flare. · Not a cure; can still transmit HIV/HBV through blood or sexual contact. Use barrier protection. |