Etravirine

Indications

Etravirine is used for: Treatment of HIV-1 infection in combination with ≥2 additional antiretroviral agents in treatment-experienced patients exhibiting viral replication with documented non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance

Adult Dose

Oral HIV infection Adult: In combination w/ other antiretroviral agents: Treatment-experienced patients: 200 mg bid.

Child Dose

Oral HIV infection Child: <2 years: Safety and efficacy not established 2 to <18 years and ?10 kg • 10 to <20 kg: 100 mg PO q12hr • 20 to <25 kg: 125 mg PO q12hr • 25 to <30 kg: 150 mg PO q12hr • >30 kg: 200 mg PO q12hr

Renal Dose

Renal Impairment No dosage adjustment required

Administration

Should be taken with food. Swallow whole, do not chew/crush. For patients w/ swallowing difficulties, disperse tab thoroughly in a glass of water & drink immediately. Rinse the glass w/ water several times & drink each rinse completely.

Contra Indications

Hypersensitivity to etravirine. Severe hepatic (Child-Pugh Class C) impairment. Lactation.

Precautions

Risk of severe skin reactions (eg, Stevens-Johnson Syndrome, erythema multiforme, toxic epidermal necrolysis) Hypersensitivity reactions including drug rash with eosinophilia and systemic symptoms (DRESS) reported; characterized by rash, constitutional findings, and sometimes organ dysfunction; discontinue if severe rash develops and initiate appropriate therapy Risk of immune reconstitution syndrome 50% decrease in absorption when administered under fasting conditions: only take with meal

Pregnancy-Lactation

Pregnancy An ART pregnancy registry has been established (1-800-258-4263); prospective pregnancy data from the Antiviral Pregnancy Registry (APR) not sufficient to adequately assess risk of birth defects or miscarriage Etravirine use during pregnancy evaluated in a limited number of individuals as reported by the APR, and available data show 1 birth defect in 66 first trimester exposures to etravirine-containing regimens Lactation The Centers for Disease Control and Prevention recommend HIV-1-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV Based on limited data, etravirine has been shown to be present in human breast milk No data on the effects of etravirine on the breastfed infant, or the effects of etravirine on milk production Because of potential for HIV-1 transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants), and adverse reactions in breastfed infants similar to those seen in adults, instruct mothers not to breastfeed during treatment

Interactions

May decrease plasma concentrations and therapeutic effects of indinavir, antiarrhythmics (e.g. amiodarone, quinidine, flecainide, systemic lidocaine, disopyramide, mexiletine, propafenone), itraconazole, ketoconazole, lovastatin, rosuvastatin, simvastatin, immunosuppressants (e.g. ciclosporin, sirolimus, tacrolimus). May increase plasma concentrations of warfarin, diazepam, digoxin. Decreased plasma concentrations w/ carbamazepine, phenobarbital, phenytoin, rifampicin, rifapentine, dexamethasone. May inhibit metabolism of clopidogrel.

Adverse Effects

Side effects of Etravirine : >10% Rash (16.9%) Nausea (13.9%) Increased LDL (13%) 1-10% GI disorders (2.3-5.2%) Fatigue (3.3%) Peripheral neuropathy (4%) Increased creatinine (2%) Diarrhea (2%) <1% Stevens-Johnson syndrome Erythema multiforme Angina Angioedema Toxic epidermal necrolysis (including reports of fatalities) Hypersensitivity reactions (including cases of hepatic failure)

Mechanism of Action

Etravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), binds to HIV-1 reverse transcriptase and subsequently blocks viral RNA- and DNA-dependent DNA polymerase activities including replication.