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Etravirine

Class: HIV Nonnucleoside Reverse Transcriptase Inhibitors
VA Class: AM800
Chemical Name: 4-{[6-amino-5-bromo-2-((4-cyanophenyl)amino)-4-pyrimidinyl]oxy}-3,5-dimethylbenzonitrile
Molecular Formula: C20H15BrN6O
CAS Number: 269055-15-4
Brands: Intelence

Medically reviewed by Drugs.com on Oct 20, 2020. Written by ASHP.

Introduction

Antiretroviral; HIV nonnucleoside reverse transcriptase inhibitor (NNRTI).

Uses for Etravirine

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients ≥6 years of age who are antiretroviral-experienced (previously treated) and have evidence of ongoing HIV-1 replication and HIV-1 resistant to an HIV NNRTI and other antiretrovirals; used in conjunction with other antiretrovirals.

Because of concerns regarding cross-resistance, use individual’s prior antiretroviral treatment and viral resistance testing to guide therapy; use in conjunction with other active antiretrovirals is associated with greater likelihood of treatment response. A regimen that includes only etravirine and HIV nucleoside reverse transcriptase inhibitors (NRTIs) not recommended in those who experienced virologic failure while receiving a previous NNRTI-containing regimen.

Concomitant use of etravirine and another NNRTI (e.g., delavirdine, efavirenz, nevirapine, rilpivirine) not recommended.

Safety and efficacy not established in antiretroviral-naive (have not previously received antiretroviral therapy) adults or pediatric patients; do not use in initial treatment regimens in such patients.

Postexposure Prophylaxis following Occupational Exposure to HIV

Postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care personnel and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.

USPHS recommends 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir disoproxil fumarate (tenofovir DF) as the preferred regimen for PEP following occupational exposures to HIV. Etravirine and 2 NRTIs is one of several alternative regimens. Preferred dual NRTI option for use in PEP regimens is emtricitabine and tenofovir DF (may be given as emtricitabine/tenofovir DF; Truvada); alternatives are tenofovir DF and lamivudine, lamivudine and zidovudine (may be given as lamivudine/zidovudine; Combivir), or zidovudine and emtricitabine.

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible. Do not delay initiation of PEP while waiting for expert consultation.

Etravirine Dosage and Administration

Administration

Oral Administration

Administer orally twice daily after a meal. Food enhances bioavailability. (See Food under Pharmacokinetics.)

Swallow tablets whole with a liquid (e.g., water); do not chew.

For patients unable to swallow tablets whole, administer as a dispersion. Place dose of tablets in 5 mL of water (enough water to cover the tablets) and stir until a uniform, milky dispersion occurs. If desired, add more water or, alternatively, orange juice or milk; do not use grapefruit juice or carbonated or warm (>40°C) beverage. Consume dispersion promptly; to ensure consumption of entire dose, rinse the glass several times with water, orange juice, or milk and swallow each rinse.

Dosage

Must be used in conjunction with other antiretrovirals.

Pediatric Patients

Treatment of HIV Infection
Antiretroviral-experienced Pediatric Patients
Oral

To avoid medication errors, use extra care in calculating dose, transcribing medication order, dispensing prescription, and providing dosing instructions.

Children 6 years to <18 years of age weighing ≥16 kg: Dosage is based on weight and should not exceed recommended adult dosage. (See Table 1.)

Table 1. Dosage of Etravirine for Pediatric Patients 6 Years to <18 Years of Age Weighing ≥16 kg

Body Weight

Dosage

16 to <20 kg

100 mg twice daily

20 to <25 kg

125 mg twice daily

25 to <30 kg

150 mg twice daily

≥30 kg

200 mg twice daily

Adults

Treatment of HIV Infection
Antiretroviral-experienced Adults
Oral

200 mg twice daily. Give dose as a single 200-mg tablet or two 100-mg tablets.

Postexposure Prophylaxis following Occupational Exposure to HIV†
Oral

200 mg twice daily. Use in conjunction with 2 NRTIs (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Special Populations

Hepatic Impairment

Dosage adjustments not necessary in patients with mild or moderate hepatic impairment (Child-Pugh class A or B). Pharmacokinetics not studied in patients with severe hepatic impairment (Child-Pugh class C); dosage recommendations not available for such patients. (See Special Populations under Pharmacokinetics.)

Dosage adjustments not necessary in HIV-infected adults coinfected with HBV and/or HCV. (See Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage adjustments not necessary. (See Special Populations under Pharmacokinetics.)

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Etravirine

Contraindications

  • Manufacturer states none known.

Warnings/Precautions

Sensitivity Reactions

Severe, potentially life-threatening and fatal skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme, reported. Hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms (DRESS) characterized by rash and systemic symptoms (sometimes involving organ dysfunction such as hepatic failure), also reported.

If severe hypersensitivity reactions (e.g., severe rash or rash with fever, malaise, fatigue, muscle or joint pain, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema) occur, immediately discontinue etravirine and initiate appropriate therapy. Monitor clinical status and liver transaminase concentrations.

Rash of mild to moderate intensity also reported; generally occurs within first few weeks of therapy and resolves with continued therapy (median duration 12–16 days).

Manufacturer states that history of rash while receiving other NNRTIs does not appear to increase the risk for etravirine-related rash.

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, facial wasting, breast enlargement, and general cushingoid appearance. Mechanisms and long-term consequences of fat redistribution unknown; causal relationship not established.

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium, M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) reported to occur in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Specific Populations

Pregnancy

Category B.

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Experts state safety and pharmacokinetic data insufficient to recommend routine use of etravirine for initial treatment regimens in antiretroviral-naive pregnant women.

Lactation

Not known whether distributed into human milk.

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

Pediatric Use

Safety and efficacy not established in pediatric patients <6 years of age.

Safety, efficacy, and pharmacokinetics evaluated in antiretroviral-experienced pediatric patients 6 years to <18 years of age weighing ≥16 kg; adverse effects were similar to those reported in adults (e.g., rash, diarrhea), although rash reported more frequently in pediatric patients. Rash generally was mild to moderate and macular/papular rash, occurred the second week of therapy, and generally was self-limiting and resolved within 1 week with continued etravirine therapy.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults.

Hepatic Impairment

Not studied in patients with severe hepatic impairment (Child-Pugh class C).

Renal Impairment

Minimal renal clearance; decrease in clearance not expected in patients with renal impairment.

Common Adverse Effects

Rash, peripheral neuropathy.

Interactions for Etravirine

Metabolized by CYP isoenzymes 3A, 2C9, and 2C19. Induces CYP3A; inhibits 2C9 and 2C19. Inhibits P-glycoprotein (P-gp).

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Potential pharmacokinetic interactions with drugs that induce or inhibit CYP3A, 2C9, or 2C19 with possible altered metabolism of etravirine.

Potential pharmacokinetic interaction with drugs that are substrates for CYP3A, 2C9, or 2C19 with possible altered metabolism of such drugs.

Drugs Affected by P-glycoprotein Transport

Potential pharmacokinetic interaction with drugs that are substrates for P-gp.

Specific Drugs

Drug

Interaction

Comments

Abacavir

No in vitro evidence of antagonistic antiretroviral effects

Avanafil

Data not available

Concomitant use not recommended

Antiarrhythmics (amiodarone, disopyramide, flecainide, systemic lidocaine, mexiletine, propafenone, quinidine)

Possible decreased antiarrhythmic agent concentrations

Use concomitantly with caution; monitor antiarrhythmic agent concentrations

Anticoagulants, oral

Possible increased warfarin concentrations

Monitor INR; adjust warfarin dosage if needed

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Possible decreased etravirine concentrations and decreased antiretroviral efficacy; decreased anticonvulsant concentrations

Concomitant use not recommended; consider alternative anticonvulsants

Antifungals, azoles

Fluconazole: Substantially increased etravirine concentrations and AUC; no clinically important change in fluconazole concentrations or AUC

Itraconazole: Possible increased etravirine concentrations and decreased itraconazole concentrations

Ketoconazole: Possible increased etravirine concentrations and decreased ketoconazole concentrations

Posaconazole: Possible increased etravirine concentrations; no change in posaconazole concentrations

Voriconazole: Substantially increased etravirine concentrations and AUC; increased voriconazole concentration and AUC

Fluconazole: Dosage adjustments not needed for either drug; use caution because of limited safety data regarding increased etravirine concentrations

Itraconazole: Adjustment of itraconazole dosage may be needed depending on other concomitantly administered drugs; consider monitoring itraconazole concentrations and response to the antifungal

Ketoconazole: Adjustment of ketoconazole dosage may be needed depending on other concomitantly administered drugs

Posaconazole: Experts state dosage adjustments not needed; manufacturer of etravirine states adjustment of posaconazole dosage may be needed depending on other concomitantly administered drugs

Voriconazole: Use caution because of limited safety data regarding increased etravirine concentrations; dosage adjustments not needed; consider monitoring voriconazole concentrations

Antimalarials

Fixed combination of artemether and lumefantrine (artemether/lumefantrine): Decreased concentrations and AUC of artemether, active metabolite of artemether (dihydroartemisinin), and lumefantrine; no clinically important effect on etravirine concentrations or AUC

Artemether/lumefantrine: Dosage adjustments not needed; use concomitantly with caution since effect on antimalarial efficacy not known; closely monitor antimalarial efficacy

Antimycobacterials (rifabutin, rifampin, rifapentine)

Rifabutin: Decreased concentrations of etravirine and rifabutin

Rifampin: Substantially decreased etravirine concentrations possible

Rifapentine: Substantially decreased etravirine concentrations possible

Rifabutin: Recommended rifabutin dosage is 300 mg daily in patients receiving etravirine without a ritonavir-boosted PI; rifabutin not recommended in patients receiving etravirine with a ritonavir-boosted PI

Rifampin: Concomitant use not recommended

Rifapentine: Concomitant use not recommended

Atazanavir

Atazanavir or ritonavir-boosted atazanavir: Increased etravirine concentrations; decreased atazanavir concentrations and possible decreased antiretroviral efficacy

No in vitro evidence of antagonistic antiretroviral effects

Atazanavir (with or without low-dose ritonavir): Do not use concomitantly

Benzodiazepines (alprazolam, diazepam)

Alprazolam: Data not available

Diazepam: Possible increased diazepam concentrations

Alprazolam: Monitor for alprazolam therapeutic effects

Diazepam: Decreased diazepam dosage may be needed

Boceprevir

Decreased etravirine AUC; increased boceprevir concentrations and AUC

Dosage adjustments not needed

Buprenorphine, buprenorphine/naloxone

Decreased buprenorphine concentrations and AUC; no effect on norbuprenorphine or etravirine concentrations

Routine buprenorphine or buprenorphine/naloxone dosage adjustments not needed; monitor for withdrawal symptoms since buprenorphine or buprenorphine/naloxone maintenance dosage adjustment may be needed in some patients

Clarithromycin

Increased etravirine concentrations; decreased clarithromycin concentrations and increased concentrations of the major metabolite (14-hydroxyclarithromycin)

Consider an alternative to clarithromycin (e.g., azithromycin) for treatment or prophylaxis of MAC

Clopidogrel

Possible decreased concentrations of the active metabolite of clopidogrel

Avoid concomitant use if possible; consider alternatives to clopidogrel

Corticosteroids (dexamethasone)

Dexamethasone: Possible decreased etravirine concentrations and decreased antiretroviral efficacy

Use concomitantly with caution; consider alternatives to dexamethasone, especially when long-term corticosteroid use anticipated

Darunavir

Ritonavir-boosted darunavir: Decreased etravirine AUC; no change in darunavir concentrations; safety and efficacy of concomitant use established in phase 3 clinical studies

No in vitro evidence of antagonistic antiretroviral effects

Ritonavir-boosted darunavir: Dosage adjustments not needed

Delavirdine

Possible increased etravirine concentrations

Do not use concomitantly

Didanosine

No effect on didanosine or etravirine concentrations

No in vitro evidence of antagonistic antiretroviral effects

Dosage adjustments not needed

Digoxin

Possible increased digoxin concentrations; no change in etravirine concentrations

If digoxin and etravirine are initiated at the same time, initiate digoxin at the lowest dosage

If etravirine is initiated in a patient already receiving digoxin, dosage adjustments not needed for either drug

Monitor serum digoxin concentrations and adjust digoxin dosage to achieve desired clinical effect

Dolutegravir

Substantially decreased dolutegravir concentrations and AUC; no apparent effect on etravirine pharmacokinetics

Effect on dolutegravir pharmacokinetics is mitigated if etravirine and dolutegravir used concomitantly with lopinavir/ritonavir or ritonavir-boosted darunavir; effect expected to be mitigated if etravirine and dolutegravir used concomitantly with ritonavir-boosted atazanavir

Do not use etravirine and dolutegravir concomitantly unless ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or lopinavir/ritonavir also included in the regimen

HIV integrase strand transference inhibitor-naive (INSTI-naive) or INSTI-experienced without INSTI resistance: Use dolutegravir 50 mg once daily with etravirine and with ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or lopinavir/ritonavir

INSTI-experienced with documented or suspected INSTI resistance: Use dolutegravir 50 mg twice daily with etravirine and with ritonavir-boosted atazanavir, ritonavir-boosted darunavir, or lopinavir/ritonavir

Efavirenz

Decreased etravirine concentrations and loss of antiretroviral efficacy

Do not use concomitantly

Elvitegravir and cobicistat

Fixed combination of elvitegravir, cobicistat, emtricitabine, and tenofovir DF (EVG/COBI/TDF/FTC): Possible altered concentrations of elvitegravir, cobicistat, and/or etravirine

EVG/COBI/TDF/FTC: Do not use concomitantly

Emtricitabine

No in vitro evidence of antagonistic antiretroviral effects

Enfuvirtide

No in vitro evidence of antagonistic antiretroviral effects

Dosage adjustments not needed

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

Possible decreased ergot alkaloid concentrations; possible inadequate treatment effect

If methylergonovine used to treat postpartum hemorrhage in a woman receiving etravirine, additional uterotonic agents may be needed

Estrogens/progestins

Hormonal contraceptives: Slight increase in ethinyl estradiol concentrations; no change in norethindrone concentrations

Dosage adjustments not needed with oral contraceptives containing ethinyl estradiol and norethindrone

Fosamprenavir

Fosamprenavir or ritonavir-boosted fosamprenavir: Substantially increased concentrations of amprenavir (active metabolite of fosamprenavir)

No in vitro evidence of antagonistic antiretroviral effects

Fosamprenavir (with or without low-dose ritonavir): Do not use concomitantly

Histamine H2-receptor antagonists

Ranitidine: Decreased etravirine concentrations

Ranitidine: Dosage adjustments not needed

HMG-CoA reductase inhibitors (statins)

Atorvastatin: Decreased atorvastatin concentrations; no change in etravirine concentrations

Fluvastatin: Possible increased fluvastatin concentrations; no change in etravirine concentrations

Lovastatin: Possible decreased lovastatin concentrations

Pitavastatin: Possible increased pitavastatin concentrations

Pravastatin: Pharmacokinetic interaction not expected

Rosuvastatin: Pharmacokinetic interaction not expected

Simvastatin: Possible decreased simvastatin concentrations

Atorvastatin: Usual etravirine and atorvastatin dosages can be used; however, may need to adjust atorvastatin dosage based on clinical response (do not exceed maximum recommended atorvastatin dosage)

Fluvastatin: May need to adjust fluvastatin dosage

Lovastatin: May need to adjust lovastatin dosage based on clinical response (do not exceed maximum recommended lovastatin dosage); if a ritonavir-boosted PI is included in the regimen, avoid use of lovastatin

Pitavastatin: May need to adjust pitavastatin dosage

Pravastatin: Dosage adjustments not needed

Rosuvastatin: Dosage adjustments not needed

Simvastatin: May need to adjust simvastatin dosage based on clinical response (do not exceed maximum recommended simvastatin dosage); if a ritonavir-boosted PI is included in the regimen, avoid use of simvastatin

Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)

Potential for decreased immunosuppressive agent concentrations

Use concomitantly with caution; therapeutic drug monitoring of immunosuppressive agent recommended; consultation with a specialist may be needed

Indinavir

Indinavir (without low-dose ritonavir): Possible decreased indinavir concentrations

No in vitro evidence of antagonistic antiretroviral effects

Do not use concomitantly without low-dose ritonavir

Lamivudine

No in vitro evidence of antagonistic antiretroviral effects

Lopinavir/ritonavir

Decreased etravirine concentrations and AUC; decreased lopinavir concentrations and AUC

No in vitro evidence of antagonistic antiretroviral effects

Because decrease in etravirine systemic exposure in patients receiving concomitant lopinavir/ritonavir is similar to that in patients receiving etravirine and concomitant ritonavir-boosted darunavir (a combination found to be safe and effective), manufacturer and experts state that dosage adjustments not needed for either drug

Maraviroc

Decreased maraviroc concentrations and AUC; no clinically important effect on etravirine concentrations or AUC

No in vitro evidence of antagonistic antiretroviral effects

Recommended maraviroc dosage is 600 mg twice daily with usual etravirine dosage, provided regimen does not include a potent CYP3A inhibitor

Methadone

No clinically important change in methadone or etravirine concentrations

Dosage adjustments not needed

Nelfinavir

Nelfinavir (without low-dose ritonavir): Possible increased nelfinavir concentrations

No in vitro evidence of antagonistic antiretroviral effects

Do not use concomitantly with etravirine without low-dose ritonavir

Nevirapine

Decreased etravirine concentrations and loss of antiretroviral efficacy

Do not use concomitantly with etravirine

Paroxetine

No change in etravirine or paroxetine concentrations

Dosage adjustments not needed

Proton pump inhibitors

Omeprazole: Increased etravirine concentrations

Omeprazole: Dosage adjustments not needed

Raltegravir

Decreased raltegravir concentrations and AUC; no clinically important effect on etravirine pharmacokinetics; clinical importance unknown

No in vitro evidence of antagonistic antiretroviral effects

Dosage adjustments not needed

Rilpivirine

Possible decreased rilpivirine concentrations; no change in etravirine concentrations

No in vitro evidence of antagonistic antiretroviral effects

Do not use concomitantly

Ritonavir

Full-dose ritonavir (600 mg twice daily): Substantial decrease in etravirine concentrations and possible loss of antiretroviral efficacy

No in vitro evidence of antagonistic antiretroviral effects

Full-dose ritonavir (600 mg twice daily): Do not use concomitantly with etravirine

Low-dose ritonavir (usually 100 mg once or twice daily): Etravirine may be used concomitantly with certain ritonavir-boosted PI regimens (i.e., ritonavir-boosted darunavir, lopinavir/ritonavir, ritonavir-boosted saquinavir); concomitant use with ritonavir-boosted atazanavir, ritonavir-boosted fosamprenavir, or ritonavir-boosted tipranavir not recommended

Saquinavir

Ritonavir-boosted saquinavir: Decreased etravirine AUC; no change in saquinavir concentrations

Decrease in systemic exposure to etravirine is similar to that in patients receiving etravirine in conjunction with ritonavir-boosted darunavir (a combination found to be safe and effective)

No in vitro evidence of antagonistic antiretroviral effects

Ritonavir-boosted saquinavir: Dosage adjustments not needed

Sildenafil

Decreased sildenafil concentrations

Usual etravirine and sildenafil dosages can be used; sildenafil dosage may need to be increased based on clinical effect

Simeprevir

Possible decreased simeprevir concentrations

Concomitant use not recommended

Stavudine

No in vitro evidence of antagonistic antiretroviral effects

St. John’s wort (Hypericum perforatum)

Possible substantially decreased etravirine concentrations and loss of antiretroviral efficacy

Concomitant use not recommended

Tadalafil

Possible decreased tadalafil concentrations

Tadalafil dosage may need to be increased based on clinical effect

Telaprevir

Decreased telaprevir concentrations and AUC; no clinically important effect on etravirine concentrations or AUC

Insufficient data to make telaprevir dosage recommendations

Tenofovir

Decreased etravirine concentrations; no change in tenofovir concentrations

No in vitro evidence of antagonistic antiretroviral effects

Dosage adjustments not needed

Tipranavir

Ritonavir-boosted tipranavir: Decreased etravirine concentrations and possible decreased antiretroviral efficacy; increased tipranavir concentrations

No in vitro evidence of antagonistic antiretroviral effects

Ritonavir-boosted tipranavir: Do not use concomitantly

Vardenafil

Possible decreased vardenafil concentrations

Vardenafil dosage may need to be increased based on clinical effect

Zidovudine

No in vitro evidence of antagonistic antiretroviral effects

Etravirine Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability is unknown.

Following oral administration in adults, peak plasma concentrations attained within approximately 2.5–4 hours.

Food

Systemic exposure is decreased by about 50% if etravirine is administered under fasting conditions compared with administration after a meal.

Effect of food on etravirine bioavailability was studied using various meals (standard, light, enhanced-fiber, high-fat); magnitude of the food effect is similar with all meal types.

Distribution

Extent

Distribution into compartments other than plasma (e.g., CSF, genital tract secretions) not evaluated.

Crosses the placenta and has been detected in cord blood.

Not known whether distributed into human milk.

Plasma Protein Binding

99.9%, principally albumin and alpha 1-acid glycoprotein.

Elimination

Metabolism

Metabolized principally in the liver by CYP isoenzymes 3A, 2C9, and 2C19.

In cell culture, the major metabolites are at least 90% less active than etravirine against wild-type HIV-1.

Elimination Route

Following oral administration of a single dose in adults, the majority (93.7%) is eliminated in feces as unchanged etravirine (81.2–86.4%). Up to 1.2% of the dose is eliminated in urine as metabolites.

Unlikely to be removed by hemodialysis or peritoneal dialysis.

Half-life

Mean terminal elimination half-life in adults is about 41 hours.

Special Populations

Renal impairment: Pharmacokinetics not studied; alterations not expected because renal clearance is minimal.

Hepatic impairment: Pharmacokinetics not altered in patients with mild or moderate hepatic impairment (Child-Pugh class A or B); not studied in patients with severe hepatic impairment (Child-Pugh class C).

HIV-infected individuals coinfected with HBV and/or HCV: Reduced clearance reported.

Geriatric individuals: Studies in those up to 77 years of age indicate no substantial differences in pharmacokinetics relative to younger adults.

Pediatric patients 6 years to <18 years of age weighing ≥16 kg: Weight-based dosage (approximately 5.2 mg/kg twice daily) results in systemic etravirine exposures similar to those reported in adults receiving 200 mg twice daily.

Pregnant patients: Pharmacokinetics not studied.

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C). Tight container; protect from moisture. Dispense and store in original container; do not remove desiccant from bottle.

Actions and Spectrum

  • Inhibits replication of HIV-1 by interfering with viral RNA- and DNA-directed polymerase activities of reverse transcriptase.

  • Highly active against wild-type HIV-1; active against some clinical HIV-1 isolates resistant to some other NNRTIs (delavirdine, efavirenz, nevirapine).

  • Different resistance profile than other NNRTIs; certain single mutations that result in class resistance to other NNRTIs may not necessarily result in etravirine resistance.

  • Cross-resistance may occur between etravirine and other commercially available NNRTIs (delavirdine, etravirine, nevirapine, rilpivirine), and is expected in patients who have virologic failure while receiving a regimen that contains etravirine.

Advice to Patients

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician. Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.

  • Importance of using in conjunction with other antiretrovirals—not for monotherapy.

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.

  • Advise patients that sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to AIDS and death.

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others. Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids), never sharing personal items that can have blood or body fluids on them (e.g., toothbrushes, razor blades), and never reusing or sharing needles.

  • Importance of reading patient information provided by the manufacturer.

  • Importance of taking etravirine twice daily after a meal. Food enhances absorption of the drug; magnitude of the food effect is similar with all meal types (standard, light, enhanced-fiber, high-fat).

  • Advise patients to swallow the tablets whole with liquid (e.g., water) without chewing. Patients unable to swallow tablets whole may disperse the tablets in 5 mL of water (enough to cover the tablets); after dispersion in water, orange juice or milk may be added to the mixture. Ingest the liquid containing the dispersed etravirine tablets immediately, then rinse the glass several times with water, orange juice, or milk and drink the rinse each time to ensure entire dose is ingested.

  • If a missed dose is remembered within 6 hours of the usually scheduled time, it should be taken after a meal as soon as possible and the next dose taken at the regularly scheduled time. If missed dose is remembered >6 hours after the scheduled time, the dose should be omitted and the next dose taken at the regularly scheduled time.

  • Advise patients that severe and potentially life-threatening rash has occurred (usually within the first few weeks of etravirine therapy). Importance of immediately contacting clinician if rash occurs. Importance of immediately discontinuing etravirine and seeking medical care if rash associated with systemic symptoms (e.g., fever, generally ill feeling, extreme tiredness, muscle or joint aches, blisters, oral lesions, eye inflammation, swelling of the face, eyes, lips, or mouth, breathing difficulties, yellowing of the eyes or skin, dark or tea colored urine, pale colored stools, nausea, vomiting, loss of appetite, or right upper quadrant tenderness/pain) occurs.

  • Advise patients that redistribution/accumulation of body fat may occur with antiretroviral therapy, with as yet unknown long-term health effects.

  • Advise patients to contact their clinician if signs or symptoms of an infection occur.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements (e.g., St. John’s wort), and any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected women not to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Etravirine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg

Intelence

Janssen

100 mg

Intelence

Janssen

200 mg

Intelence

Janssen

AHFS DI Essentials™. © Copyright 2021, Selected Revisions October 30, 2014. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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