Abacavir

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) used in combination antiretroviral therapy to treat human immunodeficiency virus type 1 (HIV-1) infection. It is available in fixed-dose combinations, such as abacavir/lamivudine, and in regimens that include a third antiretroviral agent. Abacavir is marketed under the brand Ziagen and is also available as a generic drug.

Mechanism of action: Abacavir is a carbocyclic guanosine analogue. It is phosphorylated intracellularly to abacavir triphosphate, which competes with deoxyguanosine triphosphate for incorporation into viral DNA by HIV reverse transcriptase. Once incorporated, it terminates DNA chain elongation, inhibiting viral replication.

Indications and usage: Abacavir is used as part of combination antiretroviral therapy for HIV-1 infection in adults and pediatric patients, in fixed-dose combinations or in multi-drug regimens guided by clinical guidelines.

Warnings and precautions: A hypersensitivity reaction (HSR) to abacavir is strongly associated with the presence of the HLA-B57:01 allele. Before starting abacavir, patients should be screened for HLA-B57:01; if positive, abacavir should be avoided. If HSR occurs, abacavir must be discontinued permanently. Other risks include lactic acidosis with hepatic steatosis and potential hepatotoxicity. Some observational data have suggested a possible increased risk of myocardial infarction with abacavir in certain populations; clinicians should weigh cardiovascular risk factors when selecting therapy.

Adverse effects: Common effects include nausea, vomiting, diarrhea, headache, fatigue, and rash. Serious adverse effects are primarily related to hypersensitivity reactions.

Pharmacokinetics and administration: Abacavir is well absorbed orally and is primarily metabolized by alcohol dehydrogenase and glucuronyl transferase, not by cytochrome P450 enzymes. It is excreted in the urine. Dosing varies by regimen and weight; fixed-dose combinations provide specific dosing schedules.