Etravirine

Trade Names:
Intelence
- Tablets 100 mg

Pharmacology

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Binds directly to reverse transcriptase and blocks RNA- and DNA-dependent DNA polymerase activities by disrupting the enzyme's catalytic site.

Pharmacokinetics

Absorption

T _max following oral administration is about 2.5 to 4 h. Bioavailability is unknown. Systemic exposure is decreased about 50% when taken under fasting conditions.

Distribution

Protein binding is approximately 99.9%, primarily to albumin.

Metabolism

Etravirine is metabolized by CYP2C9, CYP2C19, and CYP3A4. The major metabolites are 90% less active than etravirine.

Elimination

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 t _½ is 41 h.

Special Populations

Etravirine is primarily metabolized by the liver; however, steady-state pharmacokinetics were similar in subjects with healthy, mildly impaired, and moderately impaired hepatic function. The effect of severe hepatic function impairment has not been studied.

No difference in pharmacokinetics within the range of 18 to 77 years of age.

No pharmacokinetic difference has been noted between men and women.

No pharmacokinetic difference has been demonstrated based on race.

Pharmacokinetics have not been studied.

Indications and Usage

Treatment of HIV-1 infection in combination with other antiretroviral agents.

Contraindications

Standard considerations.

Dosage and Administration

PO 200 mg twice daily following a meal.

Storage/Stability

Store at 59° to 86°F. Protect from moisture.

Drug Interactions

Etravirine may decrease plasma levels of these agents. Use with caution.

Plasma levels may be decreased by etravirine. Do not administer without low-dose ritonavir.

Atazanavir minimum plasma levels may be reduced while etravirine plasma levels may be increased.

May induce etravirine metabolism, decreasing plasma levels and resulting in loss of efficacy. Do not coadminister.

Systemic exposure to clarithromycin may be decreased while exposure to the active metabolite, 14-hydroxy-clarithromycin, may be increased. Consider azithromycin as alternative treatment against Mycobacterium avium complex.

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.

Etravirine plasma levels may be increased. Do not coadminister.

Etravirine plasma levels may be decreased, resulting in loss of efficacy. Do not coadminister. Coadminister dexamethasone with caution or use an alternative agent.

Plasma levels may be increased by etravirine.

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.

Plasma levels of amprenavir and nelfinavir may be elevated. Do not administer these protease inhibitors with etravirine without low-dose ritonavir.

Systemic exposure to amprenavir may be increased. Do not coadminister this combination with etravirine.

Systemic exposure to etravirine may be increased. Coadminister with caution.

If etravirine is not coadministered with a protease inhibitor plus ritonavir, rifabutin 300 mg daily is recommended.

Ritonavir 600 mg twice daily may decrease etravirine plasma levels, resulting in a loss of efficacy. Do not coadminister ritonavir 600 mg twice daily.

Etravirine and voriconazole plasma levels may be increased.

Warfarin plasma levels may be increased. Monitor anticoagulant parameters.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (3%); angina pectoris, atrial fibrillation, MI, syncope (less than 2%).

CNS

Fatigue, headache, peripheral neuropathy (3%); abnormal dreams, amnesia, anxiety, confusional state, convulsion, disorientation, hyperinsomnia, hypoesthesia, insomnia, nervousness, nightmares, paresthesia, sleep disorder, sluggishness, somnolence, tremor (less than 2%).

Dermatologic

Rash (17%); dry skin, hyperhidrosis, lipohypertrophy, night sweats, prurigo, swelling face (less than 2%); erythema multiforme, hypersensitivity rash, Stevens-Johnson syndrome.

EENT

Blurred vision, vertigo (less than 2%).

GI

Nausea (14%); diarrhea (5%); abdominal pain (3%); vomiting (2%); abdominal distention, constipation, dry mouth, flatulence, gastritis, gastroesophageal reflux disease, hematemesis, pancreatitis, retching, stomatitis (less than 2%).

Genitourinary

Gynecomastia, renal failure (less than 2%).

Hematologic-Lymphatic

Anemia, hemolytic anemia (less than 2%).

Hepatic

Cytolytic hepatitis, hepatic stenosis, hepatitis, hepatomegaly (less than 2%).

Lab Tests

Elevated creatinine, glucose, lipase, LDL, pancreatic amylase, total cholesterol, and triglycerides; decreased hemoglobin, neutrophils, and platelet count.

Metabolic-Nutritional

Anorexia, diabetes mellitus, dyslipidemia (less than 2%).

Respiratory

Bronchospasm, external dyspnea (less than 2%).

Miscellaneous

Drug hypersensitivity, immune reconstitution syndrome (less than 2%).

Precautions

Pregnancy

Category B .

Lactation

Undetermined. HIV-infected mothers should not breast-feed to avoid risking potential transmission of HIV to infant.

Children

Safety and efficacy not established.

Fat redistribution

Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and cushingoid appearance, have been reported.

Immune reconstitution syndrome

Has been reported in patients treated with combination antiretroviral therapy.

Skin reactions

Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, hypersensitivity reaction, and erythema multiforme, may occur.

Overdosage

Symptoms

Experience is limited.

Patient Information

• 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, the tablets may be placed in a glass of water, stirred well until water looks milky, then drunk immediately, rinsing the glass with water several times, swallowing 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.

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