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Therapeutic Classification: antiretrovirals

Pharmacologic Classification: non nucleoside reverse transcriptase inhibitors

• HIV-1 infection in treatment-experienced patients (in combination with other antiretroviral agents).

• Binds to the enzyme reverse transcriptase, which results in disrupted viral DNA synthesis.

• Evidence of decreased viral replication and reduced viral load with slowed progression of HIV and its sequelae.

Absorption: Well absorbed following oral administration. Food enhances absorption.

Distribution: Unknown.

Protein Binding: 99.9%.

Metabolism/Excretion: Mostly metabolized by the liver (CYP3A4, CYP2C9, and CYP2C19 isoenzymes); minimal renal excretion; mostly eliminated in feces as unchanged drug and metabolites.

Half-life: 41 hr.

(blood levels)

Contraindicated in:

• Concurrent use with other NNRTIs, rifampin, rifapentine, St. John's wort
• Lactation: Breastfeeding not recommended in women infected with HIV.

Use Cautiously in:

• Concurrent use of antiarrhythmics, anticonvulsants, antifungals, clarithromycin, rifabutin, diazepam, dexamethasone, HMG CoA reductase inhibitors (statins), immunosuppressants
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Children <2 yr (safety and effectiveness not established)
• Geri: Consider age-related ↓ in organ function and body mass, concurrent disease states and medications in older adults.

CV: angina pectoris, atrial fibrillation, hypertension, MYOCARDIAL INFARCTION.

Derm: rash, DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS.

EENT: blurred vision, vertigo.

Endo: gynecomastia, hyperglycemia, hyperlipidemia.

GI: nausea, abdominal pain, anorexia, dry mouth, HEPATIC FAILURE, hepatitis, stomatitis, vomiting.

GU: renal failure.

Hemat: anemia, hemolytic anemia.

Metab: fat redistribution.

MS: hemarthrosis.

Neuro: anxiety, confusion, fatigue, headache, insomnia, peripheral neuropathy, SEIZURES, sleep disorders.
Misc: immune reconstitution syndrome.

Drug-Drug:

• Etravirine is a substrate of the CYP3A4, CYP2C9, and CYP2C19 enzyme systems; other medications that induce or inhibit these systems may be expected to alter the response to etravirine. Etravirine is an inducer of CYP3A4 and an inhibitor of CYP2C9 and CYP2C19. The effects of medications that are substrates of these enzyme systems may be altered by concurrent use.
• Concurrent use with other NNRTIs including efavirenz, nevirapine, and rilpivirine may lead to ↓ effectiveness and should be avoided.
• Concurrent use with protease inhibitors, including nelfinavir and atazanavir may lead to altered plasma levels and should be undertaken with concurrent low dose ritonavir.
• Concurrent use with higher dose ritonavir, combination tipranavir/ritonavir, and fosamprenavir/ritonavir alter levels and effectiveness of etravirine and should be avoided.
• Concurrent use with lopinavir/ritonavir may ↓ levels.
• Concurrent use of the combination saquinavir/ritonavir should be undertaken cautiously.
• When used with darunavir/cobicstat or atazanavir/cobicistat, may ↓ cobicistat levels and lead to resistance; concurrent use not recommended.
• May significantly ↓ dolutegravir levels; should only be used concomitantly when darunavir/ritonavir or lopinavir/ritonavir coadministered
• ↓blood levels and effectiveness of antiarrhythmics including amiodarone, disopyramide, flecainide, lidocaine, mexiletine, quinidine, propafenone, and quinidine; blood level monitoring recommended.
• Blood levels and effects may be ↓ by anticonvulsants including carbamazepine, phenobarbital, and phenytoin.
• Concurrent use with voriconazole may ↑ levels of both drugs; ↓ levels of itraconazole and ketoconazole; dose adjustments may be necessary.
• Concurrent use with fluconazole may ↑ levels.
• May alter levels and response to clarithromycin; other agents should be considered.
• Rifampin and rifapentine↓ blood levels and effectiveness and should be avoided; rifabutin should only be used without a protease inhibitor/ritonavir combination.
• May ↑ blood levels and sedation from diazepam; monitor for effects.
• Levels and effectiveness may be ↓ by dexamethasone; use cautiously and consider alternatives.
• May alter blood levels and effects of fluvastatin, lovastatin, and simvastatin; dose adjustments may be necessary.
• May alter blood levels and effects of cyclosporine, sirolimus, and tacrolimus; careful monitoring required.
• May ↓ the antiplatelet effects of clopidogrel.
• May ↓ buprenorphine levels.
• May ↓ levels of artemether/lumefantrine.
• May ↓ levels of elbasvir/grazoprevir; concurrent use not recommended.

Drug-Natural Products:

• St. John's wort may ↓ blood levels and effectiveness; avoid concurrent use.

• PO (Adults): 200 mg twice daily.
• PO (Children 2–17 yr and 30 kg): 200 mg twice daily.
• PO (Children 2–17 yr and 25–29 kg): 150 mg twice daily.
• PO (Children 2–17 yr and 20–24 kg): 125 mg twice daily.
• PO (Children 2–17 yr and 10–19 kg): 100 mg twice daily.

(Generic available)

• Tablets: 25 mg; 100 mg; 200 mg;

• Assess for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
• Assess patient for rash (mild to moderate rash usually occurs in the 6th wk of therapy and resolves within 1–2 wk of continued therapy). If rash is severe (extensive erythematous or maculopapular rash with moist desquamation or angioedema) or accompanied by systemic symptoms (serum sickness-like reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis), discontinue therapy immediately.

• Monitor viral load and CD4 cell count regularly during therapy.
  • Monitor liver function tests periodically during therapy. May cause ↑ serum AST, ALT concentrations.
  • May cause ↑ pancreatic amylase and lipase.
  • May cause ↑ in total cholesterol, low density lipoprotein, serum triglyceride, and glucose levels.
  • May cause ↑ serum creatinine.
  • May cause ↓ neutrophils, ↓ platelet count, anemia and hemolytic anemia.

• PO: Administer tablets twice daily following a meal; type of food does not matter. DNC: Swallow tablet whole; do not break, crush, or chew.
  • If patient has difficulty swallowing, may disperse tablet in 5 mL (1 tsp) of water, or at least enough liquid to cover the medication; stir well until water looks milky. Add 15 mL water or orange juice or milk (do not place tablets in orange juice or milk without first adding water). Avoid grapefruit juice, warm, or carbonated beverages. Once dispersed, patient should stir well and drink immediately; rinse glass with water and drink several times to ensure entire dose is consumed.

• Emphasize the importance of taking etravirine as directed, at the same time each day. It must always be used in combination with other antiretroviral drugs. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses following a meal if remembered within 6 hr of the time it is usually taken, then return to regular schedule. If more than 6 hr from time dose is usually taken, omit dose and resume dosing schedule; do not double doses. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
• Instruct patient that etravirine should not be shared with others.
• Inform patient that etravirine does not cure AIDS or prevent associated or opportunistic infections. Etravirine may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others. Advise patient that the long-term effects of etravirine are unknown at this time.
• May cause dizziness, impaired concentration, or drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Instruct patient to notify health care professional immediately if rash, signs of hypersensitivity (fever, generally ill feeling, extreme tiredness, muscle or joint aches, blisters, oral lesions, eye inflammation, facial swelling), signs and symptoms of liver problems (yellowing of skin or whites of eyes, dark or tea colored urine, pale-colored stools/bowel movements, nausea, vomiting, loss of appetite, or pain, aching, or sensitivity on right side below ribs), or signs of Immune Reconstitution Syndrome (signs and symptoms of an inflammation or infection) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
• Inform patient that changes in body fat (increased fat in upper back and neck, breast, and around back, chest, and stomach area; loss of fat from legs, arms, and face) may occur.
• Advise patients to notify health care professional if pregnancy is planned or suspected. Advise patient to avoid breast feeding during therapy. Inform women who become pregnant during therapy or take Intelence during pregnancy of pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to Intelence during pregnancy. To enroll in Antiviral Pregnancy Registry, call 1-800-258-4263.
• Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

• Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
• Decrease in viral load and increase in CD4 cell counts.

Intelence