Antiviral Agents: Lamivudine

Lamivudine

Lamivudine is a synthetic cytidine analogue used in the treatment of HIV  and HBV. Its acti-vation requires phosphorylation by cellular enzymes. Lamivudine triphosphate competitively inhibits HBV DNA polymerase and HIV reverse transcriptase and causes chain termination. It inhibits the activity of mammalian DNA polymerases with a much lower po-tency.

HIV-1 frequently acquires mutations in reverse transcriptase that result in resistance to lamivudine within 12 weeks of treatment. Mutations in the DNA polymerase of HBV are associated with decreased lamivudine efficacy and have been documented in pa-tients treated with this agent for 6 months or more.

Absorption, Metabolism, and Excretion

Lamivudine is rapidly absorbed from the gastrointesti-nal tract and has an oral bioavailability of approxi-mately 85 to 90%. Lamivudine is mainly excreted un-changed by the kidney and has an elimination half-life of 5 to 7 hours.

Clinical Uses

Lamivudine is indicated for the treatment of HIV when used in combination with other antiretroviral agents. A lower dose than that used to treat HIV is approved for the treatment of HBV. Although lamivudine initially improves histological and biochemical measures of he-patic function and reduces HBV DNA to below the lim-its of detection, withdrawal of the drug usually results in disease recurrence. Resistance appears in up to one-third of patients after 1 year of treatment.

Adverse Effects, Contraindications, and Drug Interactions

The most common adverse effects of lamivudine seen at doses used to treat HBV are mild; they include headache, malaise, fatigue, fever, insomnia, diarrhea, and upper respiratory infections. Elevated alanine aminotransferase (ALT), serum lipase, and creatine ki-nase may also occur. The safety and efficacy of lamivu-dine in patients with decompensated liver disease have not been established. Dosage adjustment is required in individuals with renal impairment. Coadministration of trimethoprim–sulfamethoxazole decreases the renal clearance of lamivudine.