Basic Profile / Key Facts
Drug Category
- Anti-HIV Agents
- Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
Dosage Forms
Indications
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.
Absorption
Rapid and extensive after oral administration (83% bioavailability)
Toxicity
Some myocardial degeneration has been noticed in rats and mice
Biotrnasformation / Drug Metabolism
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.
Contraindications
Abacavir tablets and oral solution are contraindicated in patients with previously demonstrated hypersensitivity to abacavir or any other component of the products. Following a hypersensitivity reaction to abacavir, NEVER restart Abacavir or any other abacavir-containing product. Fatal rechallenge reactions have been associated with readministration of abacavir to patients with a prior history of a hypersensitivity reaction to abacavir. Abacavir tablets and oral solution are contraindicated in patients with moderate or severe hepatic impairment.
Drug Interactions
Pharmacokinetic properties of abacavir were not altered by the addition of either lamivudine or
zidovudine or the combination of lamivudine and zidovudine. No clinically significant changes to lamivudine or
zidovudine pharmacokinetics were observed following concomitant administration of abacavir.
Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir
causing an increase in overall exposure .
The addition of methadone has no clinically significant effect on the pharmacokinetic properties of abacavir. In a
study of 11 HIV-infected patients receiving methadone-maintenance therapy (40 mg and 90 mg daily) with 600 mg of
ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased 22% (90% CI 6% to 42%).
This alteration will not result in a methadone dose modification in the majority of patients; however, an increased
methadone dose may be required in a small number of patients.
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