Non-Nucleoside Reverse Transcriptase Inhibitors: Efavirenz
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.
A third anti-HIV drug in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, efavirenz (Sustiva,DuPont), was approved for treatment of HIV infection by the US Food and Drug Administration on September 18. he new agent has excited a great deal of interest for 3 reasons: it is a once-a-day drug; it seems less prone to rapid resistance than prior members of this class of medications; and several clinical trials have shown impressive efficacy for efavirenz-based combinations. However, like all new antiretroviral agents, high hopes need to be put in the context of limited real-world experience with side effects, drug interactions, and cross-resistance. (128)

Abbreviation(s):  Generic name: Brand name: EFV efavirenz Sustiva®		USA (FDA) Adult approval date: Pediatric approval date: September 21, 1998 September 21, 1998
Pharmaceutical co.: Dupont Pharmaceuticals		Belgium: Not yet commercialized

Pharmacokinetics

Due to its long half-life (40 to 55 hours), efavirenz can be administered once daily (600 mg), with or without food. Efavirenz is metabolized by cytochrome P450 CYP3A4, and therefore affects the metabolism of the protease inhibitors. Bioavailability appears good and seems to remain stable in either fed or fasted states. The manufacturer, however, advises against taking the drug with a high-fat meal, which can significantly raise levels and perhaps precipitate toxic reactions. (106,128)

Dosing

Current dosage of efavirenz is 600 mg  once daily.(111)

Side effects

The most significant side effect is a vague sensation of disengagement, dizziness, or light-headedness. These symptoms appear to be more tolerable if efavirenz is administered just prior to bedtime, and may resolve with continued dosing. As with other NNRTIs, rash may occur. The rash is typically mild and does not require dose modification or drug discontinuation. Severe rashes (i.e., Stevens-Johnson syndrome) are rare. (106)
Although initial mutagenicity screens were negative, birth defects in monkeys exposed during gestation have led to a warning to avoid this drug during pregnancy or breastfeeding. (128)

Drug interactions

Efavirenz, like the protease inhibitors and the other NNRTIs, is metabolized by the hepatic cytochrome system. It exhibits autoinduction and inhibits the metabolism of some drugs (astemizole, cisapride, triazolam, and midazolam), which could lead to toxic accumulations.(128)
 

Interactions with other antiretroviral agents

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