lamivudine

lamivudine. Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) used as an antiretroviral medication for the treatment of HIV/AIDS and hepatitis B virus (HBV) infection. It is a key component of many combination therapy regimens, such as those including zidovudine or abacavir, and is also used for post-exposure prophylaxis. The drug works by inhibiting the reverse transcriptase enzyme, thereby preventing viral replication.

Medical uses

Lamivudine is indicated for the treatment of chronic hepatitis B virus infection in adults and children, and in combination with other antiretroviral agents for the treatment of HIV-1 infection. For HIV, it is almost always used as part of a multi-drug regimen, such as in the fixed-dose combinations Combivir (with zidovudine) and Trizivir (with zidovudine and abacavir). It is also a component of the World Health Organization's essential medicines list for first-line therapy. In the context of occupational exposure to HIV, lamivudine is part of recommended post-exposure prophylaxis regimens alongside agents like tenofovir and raltegravir.

Adverse effects

Lamivudine is generally well-tolerated, with common side effects including headache, nausea, diarrhea, and fatigue. Serious adverse effects are rare but can include lactic acidosis and severe hepatomegaly with steatosis, which are class effects of nucleoside analogues. A significant concern in treating hepatitis B virus is the potential for severe acute exacerbation of hepatitis upon discontinuation of the drug. Prolonged use in monotherapy for HBV is strongly discouraged due to the high rate of selection for resistant viral strains with mutations in the polymerase gene.

Pharmacology

Lamivudine is a synthetic nucleoside analogue of cytidine. After intracellular phosphorylation to its active triphosphate form, lamivudine triphosphate competes with natural deoxycytidine triphosphate for incorporation into the nascent viral DNA chain by reverse transcriptase. Its incorporation results in chain termination, halting DNA synthesis. The drug has high oral bioavailability and is excreted largely unchanged in the urine via organic cation transporters. Its pharmacokinetics are not significantly affected by food, but dosage adjustment is required in patients with impaired renal function.

History

Lamivudine was discovered by Bernard Belleau and his team at the McGill University and developed by the pharmaceutical company BioChem Pharma in the late 1980s. It was approved for medical use in the United States in 1995 for HIV infection following clinical trials that demonstrated its efficacy in combination with zidovudine. Approval for the treatment of hepatitis B virus followed later, in 1998. The development of lamivudine represented a significant advance in antiretroviral therapy and was a foundational component in the shift toward highly active antiretroviral therapy (HAART).

Society and culture

Lamivudine is on the World Health Organization's List of Essential Medicines. It is available as a generic medication, significantly reducing costs and improving access in low- and middle-income countries through initiatives like the President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis and Malaria. The drug has been the subject of patent disputes in several countries, impacting its availability. Its role in pre-exposure prophylaxis (PrEP) regimens has been largely superseded by newer agents like tenofovir disoproxil fumarate and emtricitabine.

Category:Antiviral drugs Category:HIV/AIDS Category:Hepatitis B