etravirine (Rx)

>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)

Postmarketing Reports

Immune system disorders: Severe hypersensitivity reactions including DRESS and cases of hepatic failure

Musculoskeletal and connective tissue disorders: Rhabdomyolysis

Skin and subcutaneous tissue disorders: Fatal cases of toxic epidermal necrolysis

Contraindications

None

Cautions

Hypersensitivity

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

Drug interactions overview

• Etravirine is a CYP3A, CYP2C9, and CYP2C19 substrate; coadministration with CYP3A, CYP2C9, and CYP2C19 inhibitors or inducers may alter efficacy or adverse reaction profile of etravirine
• Etravirine is a CYP3A inducer and CYP2C9, CYP2C19 and P-glycoprotein (Pgp) inhibitor; coadministration of CYP3A, CYP2C9, CYP2C19, or P-gp substrate may alter the efficacy or toxicity of the coadministered drug(s)

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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1

Binds directly to reverse transcriptase and blocks RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic sites

Absorption

AUC: 4380 ng·hr/mL

Peak plasma time: 2.5-4 hr

Effects of food

• AUC to etravirine was decreased by about 50% when administered under fasting conditions, as compared to when administered following a meal
• Meals contained a total caloric content ranging from 345-1160 kilocalories (17-70 grams fat)

Distribution

Protein Bound: 99.9%

Metabolism

Metabolized in liver by CYP3A4, CYP2C9, and CYP2C19

Induces CYP3A4

Inhibits CYP2C9 and CYP2C19

Elimination

Half-Life: 41 hr +/- 20 hr

Excretion: Feces (93.7% [81.2% unchanged]); urine (1.2% [86.4% unchanged])

Oral Administration

Take ONLY after a meal

Swallow tablets whole

Unable to swallow tablet whole

• Place tablet(s) in 5 mL (1 teaspoon) of water, or at least enough liquid to cover the medication; stir until water looks milky
• Add ~15 mL (1 tablespoon) of liquid (eg, water, orange juice, or milk) Do not place tablets in orange juice or milk without first adding water
• Avoid use of warm (temperature > 104°F [>40°C]) or carbonated beverages
• Drink mixture immediately
• Rinse glass several times with liquid and completely swallow the rinse each time to ensure patient takes the entire dose

Storage

Tablets: Store at 25°C (77°F); with excursions permitted to 15-30°C (59-86°F)