Clinical medicine profile
Etravirine
Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor [EPC]
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- Hypersensitivity to the active substance or excipients.
- Additional absolute contraindications are indication- and product-specific — consult SmPC.
Precautions
- Severe, potentially life threatening and fatal skin reactions have been reported.
- This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction, toxic epidermal necrolysis and erythema multiforme.
- Immediately discontinue treatment if severe hypersensitivity, severe rash or rash with systemic symptoms or liver transaminase elevations develops and monitor clinical status, including liver transaminases closely.
- ( 5.1 ) Monitor for immune reconstitution syndrome and fat redistribution.
- ( 5.3, 5.4 ) 5.1 Severe Skin and Hypersensitivity Reactions Severe, potentially life-threatening and fatal skin reactions have been reported.
- In clinical trials, these include cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme.
- Hypersensitivity reactions including Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have also been reported and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including hepatic failure.
- In Phase 3 clinical trials, Grade 3 and 4 rashes were reported in 1.3% of subjects receiving etravirine compared to 0.2% of placebo subjects.
- A total of 2.2% of HIV-1-infected subjects receiving etravirine discontinued from Phase 3 trials due to rash [see Adverse Reactions (6.1 )] .
- Rash occurred most commonly during the first 6 weeks of therapy.
- The incidence of rash was higher in females [see Adverse Reactions (6.1) ] .
- Stevens-Johnson syndrome was reported in 1.1% (2/177) of pediatric patients less than 18 years of age receiving etravirine in combination with other HIV-1 antiretroviral agents in an observational study.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
patients: 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. ( 2.1 , 2.2 , 2.4 ) Pregnant patients: 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. ( 2.2 ) Pediatric patients (2 years to less than 18 years of age and weighing at least 10 kg): dosage of etravirine is based on body weight and should not exceed the recommended adult dose. Etravirine tablets should be taken following a meal. ( 2.3 ) 2.1 Recommended Dosage in Adult Patients The recommended oral dosage of etravirine for adult patients is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. The type of food does not affect the exposure to etravirine [see Clinical Pharmacology (12.3) ] . 2.2 Recommended Dosage During Pregnancy The recommended oral dosage of etravirine for pregnant individuals is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal [see Use in Specific Populations (8.1) ] 2.3 Recommended Dosage in Pediatric Patients (2 Years to Less Than 18 Years of Age) The recommended dosage of etravirine for pediatric patients 2 years to less than 18 years of age and weighing at least 10 kg is based on body weight (see Table 1) not exceeding the recommended adult dosage. Etravirine should be taken orally, following a meal. The type of food does not affect the exposure to etravirine [see Clinical Pharmacology (12.3) ] . Table 1: Recommended Dosage of Etravirine Tablets for Pediatric Patients 2 Years to Less Than 18 Years of Age Body Weight kilograms (kg) Dose greater than or equal to 10 kg to less than 20 kg 100 mg twice daily greater than or equal to 20 kg to less than 25 kg 125 mg twice daily greater than or equal to 25 kg to less than 30 kg 150 mg twice daily greater than or equal to 30 kg 200 mg twice daily 2.4 Method of Administration Instruct patients to swallow the etravirine tablet(s) whole with liquid such as water. Patients who are unable to swallow the etravirine tablet(s) whole may disperse the tablet(s) in water. Instruct the patient to do the following: place the tablet(s) in 5 mL (1 teaspoon) of water, or at least enough liquid to cover the medication, stir well until the water looks milky, add approximately 15 mL (1 tablespoon) of liquid. Water may be used but other liquids, such as orange juice or milk, may improve taste. Patients should not place the tablets in orange juice or milk without first adding water. The use of warm (temperature greater than 104°F [greater than 40°C]) or carbonated beverages should be avoided. drink the mixture immediately, rinse the glass several times with orange juice, milk or water and completely swallow the rinse each time to make sure the patient takes the entire dose. 2.1 Recommended Dosage in Adult Patients The recommended oral dosage of etravirine for adult patients is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal. The type of food does not affect the exposure to etravirine [see Clinical Pharmacology (12.3) ] . 2.2 Recommended Dosage During Pregnancy The recommended oral dosage of etravirine for pregnant individuals is 200 mg (one 200 mg tablet or two 100 mg tablets) taken twice daily following a meal [see Use in Specific Populations (8.1) ] 2.3 Recommended Dosage in Pediatric Patients (2 Years to Less Than 18 Years of Age) The recommended dosage of etravirine for pediatric patients 2 years to less than 18 years of age and weighing at least 10 kg is based on body weight (see Table 1) not exceeding the recommended adult dosage. Etravirine should be taken orally, following a meal. The type of food does not affect the exposure to etravirine [see Clinical Pharmacology (12.3) ] . Table 1: Recommended Dosage of Etravirine Tablets for Pediatric Patients 2 Years to Less Than 18 Years of Age Body Weight kilograms (kg) Dose greater than or equal to 10 kg to less than 20 kg 100 mg twice daily greater than or equal to 20 kg to less than 25 kg 125 mg twice daily greater than or equal to 25 kg to less than 30 kg 150 mg twice daily greater than or equal to 30 kg 200 mg twice daily 2.4 Method of Administration Instruct patients to swallow the etravirine tablet(s) whole with liquid such as water. Patients who are unable to swallow the etravirine tablet(s) whole may disperse the tablet(s) in water. Instruct the patient to do the following: place the tablet(s) in 5 mL (1 teaspoon) of water, or at least enough liquid to cover the medication, stir well until the water looks milky, add approximately 15 mL (1 tablespoon) of liquid. Water may be used but other liquids, such as orange juice or milk, may improve taste. Patients should not place the tablets in orange juice or milk without first adding water. The use of warm (temperature greater than 104°F [greater than 40°C]) or carbonated beverages should be avoided. drink the mixture immediately, rinse the glass several times with orange juice, milk or water and completely swallow the rinse each time to make sure the patient takes the entire dose.
See label paediatric section if present; otherwise use paediatric formulary — do not extrapolate adult doses.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
1 INDICATIONS AND USAGE Etravirine, in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients and pediatric patients 2 years of age and older [see Microbiology (12.4) and Clinical Studies (14) ] Etravirine is a human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI) indicated for treatment of HIV-1 infection in treatment-experienced patients 2 years of age and older. (1)
Adverse effects
- sections: Severe skin and hypersensitivity reactions [see Warnings and Precautions (5.1) ] .
- Immune reconstitution syndrome [see Warnings and Precautions (5.3) ] .
- The most common adverse drug reactions of moderate to severe intensity (at least 2%) which occurred at a higher rate than placebo in adults are rash and peripheral neuropathy.
- ( 6.1 ) The most common adverse drug reactions in at least 2% of pediatric patients are rash and diarrhea.
- ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Carnegie Pharmaceuticals, LLC at 1-732-783-7010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Clinical Trials Experience in Adults The safety assessment is based on all data from 1203 subjects in the Phase 3 placebo-controlled trials, TMC125-C206 and TMC125-C216, conducted in antiretroviral treatment-experienced HIV-1-infected adult subjects, 599 of whom received etravirine tablets (200 mg twice daily).
- In these pooled trials, the median exposure for subjects in the etravirine tablets arm and placebo arm was 52.3 and 51.0 weeks, respectively.
- Discontinuations due to adverse drug reactions (ADRs) were 5.2% in the etravirine tablets arm and 2.6% in the placebo arm.
- The most frequently reported ADR at least Grade 2 in severity was rash (10.0%).
- Stevens-Johnson syndrome, drug hypersensitivity reaction and erythema multiforme were reported in less than 0.1% of subjects during clinical development with etravirine tablets [see Warnings and Precautions (5.1) ] .
- A total of 2.2% of HIV-1-infected subjects in Phase 3 trials receiving etravirine tablets discontinued due to rash.
- In general, in clinical trials, rash was mild to moderate, occurred primarily in the second week of therapy, and was infrequent after Week 4.
- Rash generally resolved within 1 to 2 weeks on continued therapy.
- The incidence of rash was higher in women compared to men in the etravirine tablets arm in the Phase 3 trials (rash ≥ Grade 2 was reported in 9/60 [15.0%] women versus 51/539 [9.5%] men
Drug interactions
Open multi-drug checker ↗- Drug interactions: It is a substrate of the cytochrome P450 enzyme system as well as being an inducer of CYP3A4 hence leading to the decrease in plasma concentrations of a number of drugs.
- Thus, it should not be co-administered with carbamazepine, phenobarbital, phenytoin, rifampin, rifabutin, St.
- Johns wort, fosamprenavir/ritonavir and a full-dose of ritonavir.
- Treatment-experienced patients lack virologic response to at least two ARV regimens, with at least one member be-longing to NRTI, NNRTI and protease inhibitor.
- Etravirine has a high genetic barrier to the emergence of viral resistance, and it maintains its antiviral activity in the presence of common NNRTI mutations[a]
- In a phase III clinical trial of Etravirine on treatment-experienced patients, 62% of patients in the Etravirine group and 44% in the placebo group achieved confirmed viral load below 50 copies per mL at week 24
Mechanism & disposition
Etravirine is an antiretroviral drug [see Microbiology (12.
Read complete mechanism
Etravirine is an antiretroviral drug [see Microbiology (12.4) ] . 12.2 Pharmacodynamics Cardiac Electrophysiology In a thorough QT/QTc study in 41 healthy subjects, etravirine tablets 200 mg twice daily or 400 mg once daily did not affect the QT/QTc interval.
Product-specific
Product-specific
See product SmPC
and Bioavailability Following oral administration, Etravirine was absorbed with a T max of about 2.5 to 4 hours. The absolute oral bioavailability of etravirine tablets are unknown. In healthy subjects, the absorption of etravirine is not affected by co-administration of oral ran...
Etravirine is about 99.9% bound to plasma proteins, primarily to albumin (99.6%) and alpha 1-acid glycoprotein (97.66% to 99.02%) in vitro . The distribution of etravirine into compartments other than plasma (e.g., cerebrospinal fluid, genital tract secretions) has not been evalu...
In vitro experiments with human liver microsomes (HLMs) indicate that etravirine primarily undergoes metabolism by CYP3A, CYP2C9, and CYP2C19 enzymes. The major metabolites, formed by methyl hydroxylation of the dimethylbenzonitrile moiety, were at least 90% less active than etra...
After single dose oral administration of 800 mg 14 C-etravirine, 93.7% and 1.2% of the administered dose of 14 C-etravirine was recovered in the feces and urine, respectively. Unchanged etravirine accounted for 81.2% to 86.4% of the administered dose in feces. Unchanged etravirin...
of etravirine was about 41 (±20) hours. Specific Populations Geriatric Patients Population pharmacokinetic analysis in HIV-infected subjects showed that etravirine pharmacokinetics are not considerably different within the age range (18 to 77 years) evaluated [see Use in Specific...
Pregnancy, lactation & diet
Use only if potential benefit justifies potential risk; prefer agents with better reproductive data when alternatives exist.
Assess infant risk vs benefit of maternal therapy; prefer agents with lactation data.
Brands & loaded prices
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Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.