indication

For use in combination with other antiretroviral drugs in the ongoing treatment of HIV-1 infection.

pharmacology

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by nevirapine. Nevirapine is, in general, only prescribed after the immune system has declined and infections have become evident. It is always taken with at least one other HIV medication such as Retrovir or Videx. The virus can develop resistance to nevirapine if the drug is taken alone, although even if used properly, nevirapine is effective for only a limited time.

mechanism of action

Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of nevirapine does not compete with template or nucleoside triphosphates.

toxicity

Symptoms of overdose include edema, erythema nodosum, fatigue, fever, headache, insomnia, nausea, pulmonaryinfiltrates, rash, vertigo, vomiting, and weight decrease.

biotransformation

Hepatic. In vivo studies in humans and in vitro studies with human liver microsomes have shown that nevirapine is extensively biotransformed via cytochrome P450 3A4 metabolism to several hydroxylated metabolites.

absorption

90% (absolute bioavailability 93 ± 9%)

half life

45 hours

route of elimination

Thus cytochrome P450 metabolism, glucuronide conjugation, and urinary excretion of glucuronidated metabolites represent the primary route of nevirapine biotransformation and elimination in humans. Only a small fraction (<5%) of the radioactivity in urine (representing <3% of the total dose) was made up of parent compound; therefore, renal excretion plays a minor role in elimination of the parent compound.

drug interactions

Acenocoumarol: Nevirapine may decrease the anticoagulant effect of acenocoumarol.

Anisindione: Nevirapine may decrease the anticoagulant effect of anisindione.

Atazanavir: Nevirapine, a strong CYP3A4 inducer, may decrease the serum concentration of atazanavir by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atazanavir if nevirapine is initiated, discontinued or dose changed.

Atorvastatin: Nevirapine, a strong CYP3A4 inducer, may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nevirapine is initiated, discontinued or dose changed.

Dicumarol: Nevirapine may decrease the anticoagulant effect of dicumarol.

Ketoconazole: Nevirapine, a strong CYP3A4 inducer, may decrease the serum concentration of ketoconazole by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of ketoconazole if nevirapine is initiated, discontinued or dose changed.

Lovastatin: The strong CYP3A4 inducer, nevirapine, may decrase the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if nevirapine is initiated, discontinued or dose changed.

Methadone: The antiretroviral agent decreases the effect of methadone

Nelfinavir: Nevirapine may decrease the effect of nelfinavir.

Quinupristin: This combination presents an increased risk of toxicity

Saquinavir: Decreases the effect of saquinavir

Simvastatin: The strong CYP3A4 inducer, nevirapine, may decrase the effect of simvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of simvastatin if nevirapine is initiated, discontinued or dose changed.

St. John's Wort: St. John's Wort decreases nevirapine effect

Telithromycin: Nevirapine may decrease the plasma concentration of Telithromycin. Consider alternate therapy.

Temsirolimus: Nevirapine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.

Tipranavir: Nevirapine, a CYP3A4 inducer, may decrease the serum concentration of Tipranavir, a CYP3A4 substrate. Monitor for changesin Tipranavir effect if Nevirapine is initiated, discontinued or dose changed.

Tramadol: Nevirapine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inducer, Nevirapine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Nevirapine is initiated, discontinued or dose changed.

Warfarin: Nevirapine may decrease the anticoagulant effect of warfarin by increasing metabolism of R-warfarin via CYP3A4.