Drug information of Etravirine

Mechanism of effect

Etravirine exerts its effects via direct inhibition of the reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1). It directly binds reverse transcriptase and consequently blocks DNA-dependent and RNA-dependent polymerase activity. Etravirine does not inhibit human DNA polymerase alpha, beta or gamma.

Pharmacodynamic

Clinical trials have shown no prolongation of QT intervals on electrocardiograms after 8 days of dosing.

Pharmacokinetics

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)

Protein Bound: 99.9%

Metabolism

Metabolized in liver by CYP3A4, CYP2C9, and CYP2C19

Induces CYP3A4

Inhibits CYP2C9 and CYP2C19

Half-Life: 41 hr +/- 20 hr

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

Drug indications

Non-nucleoside reverse transcriptase inhibitor resistant HIV-1 infection

Dosage

Adult

HIV Infection

200 mg PO q12hr

Pediatric

HIV Infection

<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

Drug contraindications

None

Side effects

Diarrhea , nausea , Creatinine increased , peripheral nephropathy , gastrointestinal disturbances , tiredness , Rash

Rash , Nausea , Increased LDL , GI disorders , Fatigue , Peripheral neuropathy , Increased creatinine , Diarrhea

Interactions

nelfinavir , Efavirenz , Tipranavir , lumacaftor and Ivacaftor , Amiodarone , Erythromycin , Everolimus , Irinotecan , Isoniazid , Trazodone , stiripentol , silodosin , Venetoclax , lumefantrine , Romidepsin , riociguat , bosutinib , tolvaptan , bedaquiline , neratinib , Cariprazine , Cobimetinib , Ceritinib , Eliglustat , Elvitegravir , rilpivirine , trabectedine , Roflumilast , Apalutamide , Sonidegib , Edoxaban , Cabozantinib , Alfuzosin , Perampanel , olaparib , Ibrutinib , Ixazomib , Doravirine , Dolutegravir , cobicistat , Delavirdine , Sofosbuvir and velpatasvir , Fostamatinib , Apremilast , Ponatinib , Lumefantrine / artemether , EMTRICITABINE , Copanlisib , Simeprevir , Ulipristal , Panobinostat , Ribociclib , Idelalisib , Ivacaftor , brigatinib , Regorafenib , Palonosetron , dasabuvir , pomalidomide , vandetanib , Osimertinib , Indinavir , ritonavir , nevirapine , paritaprevir , Fosamprenavir , Ivabradine , Afatinib , Ranolazine , Praziquantel , Darunavir , Nefazodone , Axitinib , dronedarone , Daclatasvir , Sofosbuvir , ergotamine , fentanyl , Rifabutin , Rifapentine , Lovastatin , Voriconazole , Carbamazepine , Ketoconazole , Clarithromycin , Clopidogrel , Cisapride , Sildenafil , Simvastatin , Fluvoxamine , Phenobarbital , Phenytoin , Tenofovir , Deflazacort , Dihydroergotamine , Rifampin , Cimetidine , Sirolimus , Dabrafenib , Tasimelteon , raltegravir , tezacaftor/ivacaftor , ELBASVIR/GRAZOPREVIR , glasdegib , Abemaciclib , Gefitinib , Cannabidiol , rolapitant , voxelotor , Netupitant , Capmatinib

artemether/lumefantrine, carbamazepine, cariprazine, cobimetinib, delavirdine, doravirine, efavirenz, elvitegravir/cobicistat/emtricitabine/tenofovir df, fosamprenavir, indinavir, lorlatinib, lumacaftor/ivacaftor, lumefantrine, naloxegol, nelfinavir, nevirapine, ombitasvir/paritaprevir/ritonavir, ombitasvir/paritaprevir/ritonavir & dasabuvir, panobinostat, phenobarbital, praziquantel, regorafenib, rifampin, rilpivirine, roflumilast, st john's wort, tipranavir, vandetanib, abemaciclib, afatinib, alfuzosin, amiodarone, apalutamide, apremilast, axitinib, bedaquiline, bosutinib, brigatinib, cabozantinib, ceritinib, cimetidine, cisapride, clarithromycin, clopidogrel, cobicistat, copanlisib, dabrafenib, daclatasvir, darunavir, deflazacort, dihydroergotamine, dihydroergotamine intranasal, dolutegravir, dronedarone, duvelisib, edoxaban, efavirenz, elbasvir/grazoprevir, eliglustat, elvitegravir, erdafitinib, ergotamine, erythromycin, everolimus, fentanyl, fentanyl intranasal, fentanyl iontophoretic transdermal system, fentanyl transdermal, fentanyl transmucosal, fluvoxamine, fostamatinib, glasdegib, ibrutinib, idelalisib, indinavir, irinotecan, irinotecan liposomal, isoniazid, ivabradine, ivacaftor, ivosidenib, ixazomib, ketoconazole, larotrectinib, lovastatin, macimorelin, macitentan, midostaurin, nefazodone, neratinib, netupitant/palonosetron, olaparib, osimertinib, perampanel, phenytoin, pomalidomide, ponatinib, ranolazine, ribociclib, rifabutin, rifampin, rifapentine, riociguat, ritonavir, rolapitant, romidepsin, sildenafil, silodosin, simeprevir, simvastatin, siponimod, sirolimus, sofosbuvir/velpatasvir, sonidegib, stiripentol, tezacaftor, tolvaptan, trabectedin, trazodone, ulipristal, venetoclax, vorapaxar, voriconazole

Alerts

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)

Points of recommendation

• Tell all of your health care providers that you take etravirine. This includes your doctors, nurses, pharmacists, and dentists.
• Do not run out of etravirine.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine is not a cure for HIV. Stay under the care of your doctor.
• This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• This medicine interacts with many other drugs. The chance of side effects may be raised or how well etravirine works may be lowered. Check with your doctor and pharmacist to make sure that it is safe for you to take etravirine with all of your other drugs (prescription or OTC, natural products, vitamins).
• A very bad and sometimes deadly reaction has happened with etravirine. Most of the time, this reaction has signs like fever, rash, or swollen glands with problems in body organs like the liver, kidney, blood, heart, muscles and joints, or lungs. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using etravirine while you are pregnant.

• If giving to your child, the dose of etravirine may need to be changed as your child's weight changes. Have your child's weight checked often. Talk with the doctor before changing your child's dose.

• Take after meals.
• Do not take on an empty stomach.
• Swallow whole with some water or other drink.
• Do not chew etravirine.
• You may dissolve tablets in 1 teaspoon (5 mL) of water. Stir until it looks milky and then add about 1 tablespoon (15 mL) of liquid. Water may be used but orange juice or milk may taste better. Do not use carbonated drinks. Drink right away. Rinse cup with more water, orange juice, or milk and drink. This can be done a few times to make sure the full dose has been taken.
• Do not mix etravirine in warm or hot drinks.
• Keep taking etravirine as you have been told by your doctor or other health care provider, even if you feel well.
• It is important that you do not miss or skip a dose of etravirine during treatment.

• Take a missed dose as soon as you think about it.
• If it has been 6 hours or more since the missed dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Pregnancy level

category B

Related drugs

Efavirenz , nevirapine , Delavirdine , Doravirine , rilpivirine