Class: Antiretroviral agent, NNRTI
- Tablets, oral 25 mg
- Tablets, oral 100 mg
- Tablets, oral 200 mg
Binds directly to reverse transcriptase and blocks RNA- and DNA-dependent DNA polymerase activities by disrupting the enzyme's catalytic site.
T max is approximately 2.5 to 4 h. Bioavailability is unknown. Systemic exposure is decreased by approximately 50% when taken under fasting conditions.
Protein binding is approximately 99.9%, primarily to albumin.
Etravirine is metabolized by CYP2C9, CYP2C19, and CYP3A4. The major metabolites are 90% less active than etravirine.
Elimination is 93.7% in the feces and 1.2% in the urine. 81.2% to 86.4% of the dose recovered in the feces is unchanged etravirine. Mean terminal half-life is 41 h.
Special PopulationsHepatic Function Impairment
Etravirine is primarily metabolized by the liver; however, steady-state pharmacokinetics were similar in subjects with normal, mildly impaired, and moderately impaired hepatic function. The effect of severe hepatic function impairment has not been studied.
Indications and Usage
In combination with other antiretroviral agents for the treatment of HIV-1 infection in antiretroviral treatment–experienced patients 6 y and older.
None well documented.
Dosage and AdministrationAdults
PO 200 mg twice daily.Children 6 y and older At least 16 kg to less than 20 kg
PO 100 mg twice daily.At least 20 kg to less than 25 kg
PO 125 mg twice daily.At least 25 kg to less than 30 kg
PO 150 mg twice daily.At least 30 kg
PO 200 mg twice daily.
- Tablets should be swallowed whole or may be dispersed in a glass of water. Once dispersed, stir well and drink immediately.
- Tablets should be taken following a meal.
Store at 59° to 86°F. Protect from moisture.
Drug InteractionsAmprenavir, nelfinavir
Plasma levels of amprenavir and nelfinavir may be elevated. Do not administer these protease inhibitors with etravirine without low-dose ritonavir.Antiarrhythmic agents (eg, amiodarone, bepridil, disopyramide, flecainide, lidocaine [systemic], mexiletine, propafenone, quinidine)
Concentrations of these antiarrhythmics may be decreased when coadministered with etravirine. Use with caution and monitor drug concentrations if available.Atazanavir/Ritonavir
Atazanavir minimum plasma levels may be reduced, while etravirine plasma levels may be increased. Avoid coadministration.Axitinib, efavirenz, nevirapine, St. John's wort, tipranavir/ritonavir
Etravirine plasma levels may be decreased, resulting in loss of efficacy. Do not coadminister.Buprenorphine (or buprenorphine/naloxone), methadone
Clinical monitoring for withdrawal symptoms is recommended because maintenance therapy with these agents may need to be adjusted in some patients.Carbamazepine, phenobarbital, phenytoin
May induce etravirine metabolism, decreasing plasma levels and resulting in loss of efficacy. Avoid coadministration.Clarithromycin
Systemic exposure to clarithromycin may be decreased, while exposure to the active metabolite, 14-hydroxy-clarithromycin, may be increased. Etravirine plasma concentrations and pharmacologic effects may be increased. Consider azithromycin as alternative treatment against Mycobacterium avium complex.Clopidogrel
Conversion of clopidogrel to its active metabolite may be decreased. Consider alternatives to clopidogrel treatment.Darunavir/Ritonavir, lopinavir/ritonavir, saquinavir/ritonavir
Etravirine systemic exposure may be reduced. Dosage adjustments do not appear necessary. If etravirine is administered with darunavir/ritonavir or saquinavir/ritonavir, do not coadminister rifabutin because etravirine exposure will be reduced.Delavirdine
Etravirine plasma levels may be increased. Do not coadminister.Dexamethasone
Coadminister dexamethasone with caution or use an alternative agent.Diazepam
Plasma levels may be increased by etravirine. A dosage decrease may be necessary.Digoxin
When initiating treatment with etravirine and digoxin, start with the lowest dose of digoxin. When initiating etravirine treatment in a patient on a stable digoxin regimen, no dose adjustment of etravirine or digoxin is needed. Monitor digoxin concentrations and adjust the dose as needed.Fluconazole, itraconazole, ketoconazole, posaconazole
May inhibit etravirine metabolism, resulting in elevated plasma levels. In addition, etravirine may increase itraconazole and ketoconazole metabolism, resulting in decreased plasma levels of these agents. Dose adjustments for itraconazole, ketoconazole, or posaconazole may be needed.Food
Etravirine systemic exposure is reduced approximately 50% when administered under fasting conditions compared with after a meal. Always administer etravirine after a meal.Fosamprenavir/Ritonavir
Systemic exposure to amprenavir may be increased. Do not coadminister this combination with etravirine.HMG-CoA reductase inhibitors (eg, atorvastatin, fluvastatin, lovastatin, pitavastatin, simvastatin)
Coadministration may reduce lovastatin and simvastatin plasma levels and increase fluvastatin and pitavastatin levels. Dose adjustments may be necessary. The combination of atorvastatin and etravirine may be given without dose adjustments; however, the dose of atorvastatin may need to be altered based on clinical response.Immunosuppressants (eg, cyclosporine, sirolimus, tacrolimus)
Coadminister etravirine and systemic immunosuppressants with caution because plasma concentrations of cyclosporine, sirolimus, and tacrolimus may be affected.Indinavir
Plasma levels may be decreased by etravirine. Do not administer without low-dose ritonavir.Maraviroc
Maraviroc plasma concentrations may be reduced when etravirine is administered with maraviroc in the absence of a potent CYP3A inhibitor (eg, ritonavir-boosted protease inhibitor). In this instance, the recommended maraviroc dosage is 600 mg twice daily. Maraviroc plasma concentrations may be increased when etravirine is administered with maraviroc in the presence of a potent CYP3A inhibitor. In this instance, the recommended maraviroc dosage is 150 mg twice daily.Phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil, vardenafil)
Etravirine and sildenafil may be coadministered without dose adjustment; however, the dose of sildenafil may need to be altered based on clinical effect.Rifabutin
If etravirine is not coadministered with a protease inhibitor plus ritonavir, rifabutin 300 mg daily is recommended. If etravirine is administered with darunavir/ritonavir or saquinavir/ritonavir, do not coadminister rifabutin because of the potential for reduction in etravirine exposure.Rifampin, rifapentine
May induce etravirine metabolism, decreasing plasma levels and resulting in loss of efficacy. Avoid coadministration.Ritonavir
Ritonavir 600 mg twice daily may decrease etravirine plasma levels, resulting in a loss of efficacy. Do not coadminister ritonavir 600 mg twice daily.Voriconazole
Etravirine and voriconazole plasma levels may be increased. Use with caution.Warfarin
Warfarin plasma levels may be increased. Monitor anticoagulant parameters.
Angina pectoris, atrial fibrillation, MI, syncope (less than 2%).
Peripheral neuropathy (4%); abnormal dreams, amnesia, anxiety, confusional state, convulsion, disorientation, disturbance in attention, hypersomnia, hypoesthesia, nervousness, nightmares, paresthesia, sleep disorder, sluggishness, somnolence, tremor (less than 2%).
Rash (15%); dry skin, hyperhidrosis, lipohypertrophy, night sweats, prurigo, swelling face (less than 2%); TEN (postmarketing).
Blurred vision, vertigo (less than 2%).
Abdominal distention, anorexia, constipation, dry mouth, flatulence, gastritis, gastroesophageal reflux disease, hematemesis, pancreatitis, retching, stomatitis (less than 2%).
Acute renal failure, gynecomastia (less than 2%).
Hemolytic anemia (less than 2%).
Cytolytic hepatitis, hepatic failure, hepatic stenosis, hepatitis, hepatomegaly (less than 2%).
Elevated total cholesterol (20%); elevated glucose (15%); elevated LDL (13%); elevated triglycerides (9%); elevated pancreatic amylase (7%); elevated ALT, AST, and creatinine (6%); decreased neutrophils (5%); elevated lipase (4%); decreased platelet count (3%); decreased Hgb, decreased WBC (2%).
Diabetes mellitus, dyslipidemia (less than 2%).
Bronchospasm, external dyspnea (less than 2%).
Drug hypersensitivity, immune reconstitution syndrome (less than 2%); severe hypersensitivity reactions (including cases of hepatic failure); rhabdomyolysis (postmarketing).
Monitor clinical status, including liver transaminases, in patients who develop signs and symptoms of severe skin reactions (eg, Stevens-Johnson syndrome, TEN) or hypersensitivity reactions.
Category B .
Undetermined. HIV-infected mothers should not breast-feed to avoid potential transmission of HIV to infant.
Safety and efficacy in children younger than 6 y have not been established.
Has been reported and was characterized by constitutional reactions, rash, and sometimes organ dysfunction, including hepatic failure.
Redistribution/accumulation of body fat, including breast enlargement, central obesity, cushingoid appearance, dorsocervical fat enlargement (buffalo hump), and peripheral wasting, have been reported.
Immune reconstitution syndrome
Has been reported in patients treated with combination antiretroviral therapy.
Severe, potentially life-threatening, and fatal skin reactions, including Stevens-Johnson syndrome, TEN, and erythema multiforme, may occur.
Experience is limited.
- Warn patient that this drug is not to be used by itself, but in combination with other antiretroviral agents, and not to change the dose or stop taking any other antiviral agents unless advised by health care provider.
- Advise patient not to take etravirine on an empty stomach and that the type of food is not important.
- Advise patients to take tablets whole with a liquid, such as water, and not to chew the tablets. If the tablets cannot be swallowed whole, they may be placed in a glass of water and stirred well until water looks milky. Advise patient to drink immediately, rinse the glass with water several times, and swallow the rinse each time to make sure the entire dose is taken.
- Advise patient that etravirine may cause changes in body fat distribution and that the cause and long-term health effects of these changes are not known at this time. Advise patient to report changes in body fat distribution to heath care provider.
- Advise patient that etravirine does not completely eliminate HIV virus and, therefore, does not reduce the risk of transmitting HIV to others. Appropriate precautions (eg, practicing safer sex using a latex or polyurethane condom) must be followed.
- Advise patients that if a dose is missed within 6 h of the time they usually take the dose, to take the missed dose following a meal as soon as possible. Then, take the next dose at the regularly scheduled time. If a dose is missed by more than 6 h of the usual administration time, the patient should wait and take the next dose at the regularly scheduled time. The dose should not be doubled to make up for the missed dose.
- Advise patients that severe and potentially life-threatening rash has been reported with etravirine. Advise patients to contact their health care provider immediately if they develop a rash. Instruct patients to immediately stop taking etravirine and seek medical attention if the rash is associated with any of the following symptoms: blisters, extreme tiredness, eye inflammation, facial swelling, fever, general ill feeling, muscle or joint aches, oral lesions, or signs of liver problems.
Copyright © 2009 Wolters Kluwer Health.