EFAVIRENZ capsule

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

EFAVIRENZ (UNII: JE6H2O27P8) (EFAVIRENZ - UNII:JE6H2O27P8)

Available from:

Rising Pharma Holdings, Inc.

INN (International Name):

EFAVIRENZ

Composition:

EFAVIRENZ 50 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Efavirenz capsules in combination with other antiretroviral agents are indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and in pediatric patients at least 3 months old and weighing at least 3.5 kg. - Efavirenz capsules are contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of this product. - Coadministration of efavirenz with elbasvir and grazoprevir is contraindicated [see Warnings and Precautions (5.1)  and Drug Interactions (7.1) ]. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to efavirenz during pregnancy. Physicians are encouraged to register patients by calling the Antiretroviral Pregnancy Registry at 1-800-258-4263. Risk Summary There are retrospective case reports of neural tube defects in infants whose mothers were exposed to efavirenz-containing regimens in the first trimester of pregnancy. Prospective pregnancy data from the Antiretroviral Pregnancy Registry are not sufficient to adequately assess this risk. Available data from the Antiretroviral Pregnancy Registry show no difference in the risk of overall major birth defects compared to the background rate for major birth defects of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP). Although a causal relationship has not been established between exposure to efavirenz in the first trimester and neural tube defects, similar malformations have been observed in studies conducted in monkeys at doses similar to the human dose. In addition, fetal and embryonic toxicities occurred in rats, at a dose ten times less than the human exposure at recommended clinical dose. Because of the potential risk of neural tube defects, efavirenz should not be used in the first trimester of pregnancy. Advise pregnant women of the potential risk to a fetus. Data Human Data There are retrospective postmarketing reports of findings consistent with neural tube defects, including meningomyelocele, all in infants of mothers exposed to efavirenz-containing regimens in the first trimester. Based on prospective reports from the Antiretroviral Pregnancy Registry (APR) of approximately 1000 live births following exposure to efavirenz-containing regimens (including over 800 live births exposed in the first trimester), there was no difference between efavirenz and overall birth defects compared with the background birth defect rate of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program. As of the interim APR report issued December 2014, the prevalence of birth defects following first-trimester exposure was 2.3% (95% CI: 1.4% to 3.6%). One of these prospectively reported defects with first-trimester exposure was a neural tube defect. A single case of anophthalmia with first-trimester exposure to efavirenz has also been prospectively reported. This case also included severe oblique facial clefts and amniotic banding, which have a known association with anophthalmia. Animal Data Effects of efavirenz on embryo-fetal development have been studied in three nonclinical species (cynomolgus monkeys, rats, and rabbits). In monkeys, efavirenz 60 mg/kg/day was administered to pregnant females throughout pregnancy (gestation days 20 through 150). The maternal systemic drug exposures (AUC) were 1.3 times the exposure in humans at the recommended clinical dose (600 mg/day), with fetal umbilical venous drug concentrations approximately 0.7 times the maternal values. Three of 20 fetuses/infants had one or more malformations; there were no malformed fetuses or infants from placebo-treated mothers. The malformations that occurred in these three monkey fetuses included anencephaly and unilateral anophthalmia in one fetus, microphthalmia in a second, and cleft palate in the third. There was no NOAEL (no observable adverse effect level) established for this study because only one dosage was evaluated. In rats, efavirenz was administered either during organogenesis (gestation days 7 to 18) or from gestation day 7 through lactation day 21 at 50, 100, or 200 mg/kg/day. Administration of 200 mg/kg/day in rats was associated with increase in the incidence of early resorptions; and doses 100 mg/kg/day and greater were associated with early neonatal mortality. The AUC at the NOAEL (50 mg/kg/day) in this rat study was 0.1 times that in humans at the recommended clinical dose. Drug concentrations in the milk on lactation day 10 were approximately 8 times higher than those in maternal plasma. In pregnant rabbits, efavirenz was neither embryo lethal nor teratogenic when administered at doses of 25, 50, and 75 mg/kg/day over the period of organogenesis (gestation days 6 through 18). The AUC at the NOAEL (75 mg/kg/day) in rabbits was 0.4 times that in humans at the recommended clinical dose. Risk Summary The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. Because of the potential for HIV transmission in breastfed infants, advise women not to breastfeed. Because of potential teratogenic effects, pregnancy should be avoided in women receiving efavirenz [see Use in Specific Populations (8.1)]. Pregnancy Testing Females of reproductive potential should undergo pregnancy testing before initiation of efavirenz. Contraception Females of reproductive potential should use effective contraception during treatment with efavirenz and for 12 weeks after discontinuing efavirenz due to the long half-life of efavirenz. Barrier contraception should always be used in combination with other methods of contraception. Hormonal methods that contain progesterone may have decreased effectiveness [see Drug Interactions (7.1)] . The safety, pharmacokinetic profile, and virologic and immunologic responses of efavirenz were evaluated in antiretroviral-naive and -experienced HIV-1 infected pediatric patients 3 months to 21 years of age in three open-label clinical trials [see Adverse Reactions (6.2), Clinical Pharmacology (12.3), and Clinical Studies (14.2)]. The type and frequency of adverse reactions in these trials were generally similar to those of adult patients with the exception of a higher frequency of rash, including a higher frequency of Grade 3 or 4 rash, in pediatric patients compared to adults [see Warnings and Precautions (5.8)  and Adverse Reactions (6.2)]. Use of efavirenz in patients younger than 3 months of age OR less than 3.5 kg body weight is not recommended because the safety, pharmacokinetics, and antiviral activity of efavirenz have not been evaluated in this age group and there is a risk of developing HIV resistance if efavirenz is underdosed. See  Dosage and Administration (2.2) for dosing recommendations for pediatric patients. Clinical studies of efavirenz did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from 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 therapy. Efavirenz is not recommended for patients with moderate or severe hepatic impairment because there are insufficient data to determine whether dose adjustment is necessary. Patients with mild hepatic impairment may be treated with efavirenz without any adjustment in dose. Because of the extensive cytochrome P450-mediated metabolism of efavirenz and limited clinical experience in patients with hepatic impairment, caution should be exercised in administering efavirenz to these patients [see  Warnings and Precautions (5.9)  and Clinical Pharmacology (12.3) ] .

Product summary:

Efavirenz capsules USP are available as follows: Efavirenz capsules USP 50 mg are Yellow/White size ‘4’ hard gelatin capsules imprinted with ‘D’ on yellow cap and ‘72’ on white body with black edible ink filled with white to off-white colored powder. Bottles of 30               NDC 64980-406-03 Efavirenz capsules USP 200 mg are Yellow/Yellow size ‘0EL’ hard gelatin capsules imprinted with ‘D’ on yellow cap and ‘36’ on yellow body with black edible ink filled with white to off-white colored powder. Bottles of 90               NDC 64980-407-09 Efavirenz capsules should be stored at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

EFAVIRENZ - EFAVIRENZ CAPSULE
RISING PHARMA HOLDINGS, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO
USE EFAVIRENZ CAPSULES SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
EFAVIRENZ CAPSULES.
EFAVIRENZ CAPSULES FOR ORAL USE
INITIAL U.S. APPROVAL: 1998
INDICATIONS AND USAGE
Efavirenz is a non-nucleoside reverse transcriptase inhibitor
indicated in combination with other
antiretroviral agents for the treatment of human immunodeficiency
virus type 1 infection in adults and in
pediatric patients at least 3 months old and weighing at least 3.5 kg.
(1)
DOSAGE AND ADMINISTRATION
Efavirenz capsules should be taken orally once daily on an empty
stomach, preferably at bedtime. (2)
Recommended adult dose: 600 mg. (2.2)
With voriconazole, increase voriconazole maintenance dose to 400 mg
every 12 hours and decrease
efavirenz dose to 300 mg once daily using the capsule formulation.
(2.2)
With rifampin, increase efavirenz capsules dose to 800 mg once daily
for patients weighing 50 kg or
more. (2.2)
Pediatric dosing is based on weight. (2.3)
DOSAGE FORMS AND STRENGTHS
Capsules: 50 mg and 200 mg. (3)
CONTRAINDICATIONS
Patients with previously demonstrated hypersensitivity (e.g.,
Stevens-Johnson syndrome, erythema
multiforme, or toxic skin eruptions) to any of the components of this
product. (4)
Coadministration of efavirenz with elbasvir/grazoprevir.
WARNINGS AND PRECAUTIONS
_QTc prolongation:_ Consider alternatives to efavirenz in patients
taking other medications with a known
risk of Torsade de Pointes or in patients at higher risk of Torsade de
Pointes. (5.2)
_Do not use as a single agent _or add on as a sole agent to a failing
regimen. Consider potential for
cross-resistance when choosing other agents. (5.3)
Not recommended with ATRIPLA, which contains efavirenz, emtricitabine,
and tenofovir disoproxil
fumarate, unless needed for dose adjustment when coadministered with
rifampin. (5.4)
_Serious psychiatric symptoms: _Immediate medical evaluation