Approved January 18, 2008

ETRAVIRINE
(FDA Category 1S)

INTELENCE(TM) (Tibotec Therapeutics) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1) antiretroviral agent that binds directly to reverse transcriptase and blocks the RNA-dependent and DNA-dependent DNA polymerase activities.

DOSING INFORMATION: The recommended dose of etravirine is 200 milligrams taken orally twice a day following a meal.

PHARMACOKINETICS: The absolute oral bioavailability is unknown. The systemic exposure to etravirine was decreased by approximately 50% when administered under fasting conditions compared to administration after a meal, therefore, etravirine should always be administered following a meal. Etravirine is highly protein bound, primarily to albumin (99.6%) and alpha 1-acid glycoprotein (97.66% to 99.02%). Etravirine is primarily metabolized by the liver via CYP3A4, CYP2C9, and CYP2C19 enzymes. About 94% of etravirine is excreted in the feces (81 to 86% unchanged). The mean elimination half-life of etravirine is approximately 41 hours.

CAUTIONS: Severe skin reactions, including Stevens-Johnson syndrome, hypersensitivity reaction and erythema multiforme have been reported. The most common side effects are peripheral neuropathy, paraesthesia, nausea, abdominal pain, rash, and increased liver enzymes. Coadministration with protease inhibitors (without ritonavir); tipranavir/ritonavir, fosamprenavir/ritonavir, atazanavir/ritonavir and with other non-nucleoside reverse transcriptase inhibitors is not recommended.

FDA APPROVED INDICATIONS: Etravirine is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection among antiretroviral treatment-experienced adults who have evidence of viral replication and HIV-1 strains resistant to a NNRTI and other antiretroviral agents.