n humans at the recommended clinical dose (600 mg/day), with fetal umbilical venous drug concentrations approximately 0.7 times the maternal values. Three fetuses 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, microophthalmia 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 eva luated. 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.
The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1. Studies in rats have demonstrated that both efavirenz and tenofovir are secreted in milk. It is not known whether efavirenz, emtricitabine, or tenofovir is excreted in human milk. Because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving ATRIPLA.
ATRIPLA should only be administered to pediatric patients 12 years of age and older with a body weight greater than or equal to 40 kg (greater than or equal to 88 lbs). Because ATRIPLA is a fixed-dose combination tablet, the dose adjustments recommended for pediatric patients younger than 12 years of age for each individual component cannot be made with ATRIPLA [See Warnings and Precautions (5.9, 5.11), Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].
Clinical trials of efavirenz, emtricitabine, or tenofovir DF did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for the elderly patients should be cautious, keeping in mind the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
ATRIPLA is not recommended for patients with moderate or severe hepatic impairment because there are insufficient data to determine an appropriate dose. Patients with mild hepatic impairment may be treated with ATRIPLA at the approved 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 ATRIPLA to these patients [See Warnings and Precautions (5.10) and Clinical Pharmacology (12.3)].
Because ATRIPLA is a fixed-dose combination, it should not be prescribed for patients req |
