ETRAVIRINE tablet

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

ETRAVIRINE (UNII: 0C50HW4FO1) (ETRAVIRINE - UNII:0C50HW4FO1)

Tilgjengelig fra:

Amneal Pharmaceuticals NY LLC

Administreringsrute:

ORAL

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

Etravirine tablets, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients and pediatric patients 6 years of age and older [see Microbiology (12.4) and Clinical Studies (14)] . Additional pediatric use information is approved for Janssen Products, LP’s INTELENCE® (etravirine) tablets. However, due to Janssen Products, LP’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. None. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to etravirine during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Prospective pregnancy data from clinical trials and the APR are not sufficient to adequately assess the risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Etravirine use during pregnancy has been evaluated in a limited number of individuals as reported by the APR, and available data show 1 birth defect in 66 first trimester exposures to etravirine-containing regimens (see Data) . The estimated background rate for major birth defects is 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. The background risk of major birth defects and miscarriage for the indicated population is unknown. In animal reproduction studies, no adverse developmental effects were observed with orally administered etravirine at exposures equivalent to those at the maximum recommended human dose (MRHD) of 400 mg daily (see Data) . Data Human Data Based on prospective reports to the APR of 116 live births following exposure to etravirine-containing regimens during pregnancy (including 66 exposed in the first trimester and 38 exposed in the second/third trimester), the number of birth defects in live births for etravirine was 1 out of 66 with first trimester exposure and 0 out of 38 with second/third trimester exposure. Prospective reports from the APR of overall major birth defects in pregnancies exposed to etravirine are compared with a U.S. background major birth defect rate. Methodological limitations of the APR include the use of MACDP as the external comparator group. Limitations of using an external comparator include differences in methodology and populations, as well as confounding due to the underlying disease; these limitations preclude an accurate comparison of outcomes. Etravirine (200 mg twice daily) in combination with other antiretroviral agents was evaluated in a clinical trial enrolling 15 pregnant subjects during the second and third trimesters of pregnancy and postpartum. Thirteen subjects completed the trial through postpartum period (6 to 12 weeks after delivery). The pharmacokinetic data demonstrated that exposure to total etravirine was generally higher during pregnancy compared with postpartum [see Clinical Pharmacology (12.3)] . Among subjects who were virologically suppressed (HIV-1 RNA less than 50 copies/mL) at baseline (9/13), virologic suppression was maintained through the third trimester and postpartum period. Among subjects with HIV-1 RNA greater than 50 copies/mL and less than 400 copies/mL at baseline (3/13), viral loads remained less than 400 copies/mL. In one subject with HIV-1 RNA greater than 1,000 copies/mL at baseline (1/13), HIV-1 RNA remained greater than 1,000 copies/mL during the study period. Thirteen infants were born to 13 HIV-infected pregnant individuals in this study. HIV-1 test results were not available for 2 infants. Among the eleven infants with HIV-1 test results available, who were born to 11 HIV-infected pregnant individuals who completed the study, all had test results that were negative for HIV-1 at the time of delivery. No unexpected safety findings were observed compared with the known safety profile of etravirine in non-pregnant adults. Animal Data Reproductive and developmental toxicity studies were performed in rats (at 250, 500 and 1,000 mg/kg/day) and rabbits (at 125, 250 and 375 mg/kg/day) administered etravirine on gestation days 6 through 16, and 6 through 19, respectively. In both species, no treatment-related embryo-fetal effects were observed. In addition, no treatment-related effects were observed in a pre- and postnatal development study performed in rats administered oral doses up to 500 mg/kg/day on gestation days 7 through lactation day 7. The systemic drug exposures achieved at the high dose in these animal studies were equivalent to those at the MRHD. Risk Summary The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. Based on limited data, etravirine has been shown to be present in human breast milk. There are no data on the effects of etravirine on the breastfed infant, or the effects of etravirine on milk production. Because of the potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants) and (3) adverse reactions in breastfed infants similar to those seen in adults, instruct mothers not to breastfeed if they are receiving etravirine. The safety and effectiveness of etravirine have been established for the treatment of HIV-infected pediatric patients from 6 years of age to less than 18 years [see Indications and Usage (1) and Dosage and Administration (2.3)] . Use of etravirine in pediatric patients 6 years to less than 18 years of age is supported by evidence from adequate and well-controlled studies of etravirine in adults with additional data from a Phase 2 trial in treatment-experienced pediatric subjects, TMC125-C213, 6 years to less than 18 years of age (N=101). The study was an open-label, single arm trial of etravirine plus an optimized background regimen. In the clinical trial, the safety, pharmacokinetics, and efficacy were comparable to that observed in adults except for rash (greater than or equal to Grade 2) which was observed more frequently in pediatric subjects [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.2)] . Postmarketing reports of Stevens-Johnson syndrome in pediatric patients receiving etravirine have been reported [see Warnings and Precautions (5.1), and Adverse Reactions (6.2) ]. Treatment with etravirine is not recommended in pediatric patients less than 2 years of age [see Clinical Pharmacology (12.3)] . Additional pediatric use information is approved for Janssen Products, LP’s INTELENCE® (etravirine) tablets. However, due to Janssen Products, LP’s marketing exclusivity rights, this drug product is not labeled with that pediatric information. Clinical studies of etravirine did not include sufficient numbers of subjects aged 65 years of age and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)] . No dose adjustment of etravirine is required in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. The pharmacokinetics of etravirine have not been evaluated in patients with severe hepatic impairment (Child-Pugh Class C) [see Clinical Pharmacology (12.3)] . Since the renal clearance of etravirine is negligible (less than 1.2%), a decrease in total body clearance is not expected in patients with renal impairment. No dose adjustments are required in patients with renal impairment. As etravirine is highly bound to plasma proteins, it is unlikely that it will be significantly removed by hemodialysis or peritoneal dialysis [see Clinical Pharmacology (12.3)] .

Produkt oppsummering:

Etravirine Tablets, 25 mg are supplied as white to off-white, oval shaped, uncoated tablets containing 25 mg of etravirine. Each tablet is debossed with “A56” on one side and score on the other side. They are available as follows: Bottles of 120 with child-resistant closure:                NDC 69238-1720-7 Each bottle contains 2 desiccant pouches. Etravirine Tablets, 100 mg are supplied as white to off-white, oval shaped, uncoated tablets containing 100 mg of etravirine. Each tablet is debossed with “AC75” on one side and plain on the other side. They are available as follows: Bottles of 120 with child-resistant closure:                NDC 69238-1721-7 Each bottle contains 3 desiccant pouches. Etravirine Tablets, 200 mg are supplied as white to off-white, oval shaped, uncoated tablets containing 200 mg of etravirine. Each tablet is debossed with “AC76” on one side and plain on the other side. They are available as follows: Bottles of 60 with child-resistant closure:                  NDC 69238-1722-6 Each bottle contains 3 desiccant pouches. Store etravirine tablets at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP controlled room temperature]. Store in the original bottle. Keep the bottle tightly closed in order to protect from moisture. Do not remove the desiccant pouches.

Autorisasjon status:

Abbreviated New Drug Application

Preparatomtale

ETRAVIRINE- ETRAVIRINE TABLET
AMNEAL PHARMACEUTICALS NY LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ETRAVIRINE TABLETS
SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
ETRAVIRINE TABLETS.
ETRAVIRINE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2008
INDICATIONS AND USAGE
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 6 years of age and
older. (1)
(1)
DOSAGE AND ADMINISTRATION
Adult 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 (6 years to less than 18 years of age and weighing
at least 16 kg): dosage of
etravirine tablets are based on body weight and should not exceed the
recommended adult dose.
Etravirine tablets should be taken following a meal. (2.3)
DOSAGE FORMS AND STRENGTHS
Tablets: 25 mg, 100 mg, and 200 mg (3)
CONTRAINDICATIONS
None. (4)
(4)
WARNINGS AND 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)
ADVERSE REACTIONS
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 ADVE