indication

For the treatment of HIV-1 infection, in combination with other antiretroviral agents.

pharmacology

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Abacavir is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.

mechanism of action

Abacavir is a carbocyclic synthetic nucleoside analogue. Intracellularly, abacavir is converted by cellular enzymes to the active metabolite carbovir triphosphate, an analogue of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.

toxicity

Some myocardial degeneration has been noticed in rats and mice

biotransformation

Hepatic, by alcohol dehydrogenase and glucuronosyltransferase to a 5′-carboxylic acid metabolite and 5′-glucuronide metabolite, respectively. These metabolites have no antiviral activity. Abacavir is not significantly metabolized by cytochrome P450 enzymes.

absorption

Rapid and extensive after oral administration (83% bioavailability)

half life

1.54 ± 0.63 hours

route of elimination

Elimination of abacavir was quantified in a mass balance study following administration of a 600-mg dose of 14C-abacavir: 99% of the radioactivity was recovered, 1.2% was excreted in the urine as abacavir, 30% as the 5′-carboxylic acid metabolite, 36% as the 5′-glucuronide metabolite, and 15% as unidentified minor metabolites in the urine. Fecal elimination accounted for 16% of the dose. Fecal elimination accounted for 16% of the dose. Renal excretion of unchanged abacavir is a minor route of elimination in humans.

drug interactions

Amprenavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Amprenavir. The antiviral response should be closely monitored.

Atazanavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Atazanavir. The antiviral response should be closely monitored.

Darunavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Darunavir. The antiviral response should be closely monitored.

Ethanol: Abacavir is partly metabolized through the alcohol dehydrogenase enzyme system. Alcohol increases the area under the curve (about 41%) of Abacavir. Interaction does not appear to be clinically significant.

Fosamprenavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Fosamprenavir. The antiviral response should be closely monitored.

Ganciclovir: The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Abacavir, may be enhanced by Ganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is required.

Indinavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Indinavir. The antiviral response should be closely monitored.

Lopinavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Lopinavir. The antiviral response should be closely monitored.

Nelfinavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Nelfinavir. The antiviral response should be closely monitored.

Ribavirin: Ribavirin may increase the hepatotoxicity of reverse transcriptase inhibitors (nucleoside) such as Abacavir. Lactic acidosis may occur. Consider modifying therapy.

Ribavirin Monophosphate: Ribavirin Monophosphate may increase the hepatotoxicity of reverse transcriptase inhibitors (nucleoside) such as Abacavir. Lactic acidosis may occur. Consider modifying therapy.

Ritonavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Ritonavir. The antiviral response should be closely monitored.

Saquinavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Saquinavir. The antiviral response should be closely monitored.

Tipranavir: The serum concentration of Abacavir may be decreased by protease inhibitors such as Tipranavir. The antiviral response should be closely monitored.

Valganciclovir: The adverse/toxic effects of reverse transcriptase inhibitors (nucleoside), such as Abacavir, may be enhanced by Valganciclovir. There is a risk of hematologic toxicity. Diligent monitoring during concomitant therapy is recommended.