Nucleoside Reverse Transcriptase Inhibitors: Abacavir
Contents Introduction Information card Pharmacokinetics Dosing Side effects Drug interactions

Introduction

The information represented on this drug does not necessarily correspond with the information that can be found in the Belgian scientific leaflet.
In December, the US Food and Drug Administration granted approval of abacavir, a nucleoside analogue HIV-1 reverse transcriptase inhibitor. Abacavir offers the promise of several important clinical differences as well as a unique side-effect challenge. (119)

Abbreviation(s):  Generic name: Brand name: ABC abacavir Ziagen®		USA (FDA) Adult approval date: Pediatric approval date: December 17, 1998 December 17, 1998
Pharmaceutical co.: Glaxo Wellcome Inc.		Belgium: Not yet a price neither reimbusable.

Pharmacokinetics

Like the other nucleoside analogues, it requires intracellular triphosphorylation for activation, but it uses a unique pathway and therefore will not compete with other drugs. According to the manufacturer, the drug's plasma and intracellular half-lives are 1.5 and 3.3 hours, respectively, supporting twice-daily administration. Central nervous system penetration is very good, with CSF to plasma ratios in the range of 30% to 44% (suggesting it may suppress HIV replication in a compartment that appears to be inaccessible to current potent therapies). Two metabolic pathways are known: glucuronidation and carboxylation via alcohol dehydrogenase. (106,119)

Dosing

Current dosage of abacavir is 300 mg twice daily (with or without food).(106)

Side effects

The major safety concern with abacavir is a unique, uncommon, but potentially severe hypersensitivity reaction that will require specific educational efforts aimed at both patients and providers. The syndrome is described as a multisystem process, characterized by several of the following features: fever, nausea and vomiting, malaise, and a maculopapular or urticarial rash. Estimated frequency is about 3%, and onset is typically within the first 6weeks on the drug. Laboratory abnormalities have included lymphopenia, liver function test (LFT) increases, and occasionally elevated creatine kinase (CK) levels or thrombocytopenia. Symptoms typically worsen with continued dosing but resolve promptly in several days when the drug is withheld. The real danger is a fulminant process that may ensue with rechallenge; multi-organ system failure and at least 1 death have been reported. The key seems to be to distinguish trivial or unrelated events from early hypersensitivity and then to make sure there is no rechallenge. (119)

Drug interactions

Abacavir does not alter ethanol metabolism, but alcohol does decrease abacavir clearance, producing a 40% increase in the area-under-the-concentration time curve.  (119)
 

Interactions with other antiretroviral agents

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