Tazarotene

No formal drug-drug interaction studies were conducted with TAZORAC Cream. In a trial of 27 healthy female subjects between the ages of 20–55 years receiving a combination oral contraceptive tablet containing 1 mg norethindrone and 35 mcg ethinyl estradiol, concomitant use of tazarotene administered as 1.1 mg orally (mean ± SD C max and AUC 0-24 of tazarotenic acid were 28.9 ± 9.4 ng/mL and 120.6 ± 28.5 ng • hr/mL) did not affect the pharmacokinetics of norethindrone and ethinyl estradiol over a complete cycle. The impact of tazarotene on the pharmacokinetics of progestin only oral contraceptives (i.e., minipills) has not been evaluated.

8.1 Pregnancy Risk Summary Based on data from animal reproduction studies, retinoid pharmacology, and the potential for systemic absorption, TAZORAC Cream may cause fetal harm when administered to a pregnant female and is contraindicated during pregnancy. Safety in pregnant females has not been established. The potential risk to the fetus outweighs the potential benefit to the mother from TAZORAC Cream during pregnancy; therefore, TAZORAC Cream should be discontinued as soon as pregnancy is recognized [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ), Clinical Pharmacology ( 12.3 )].

Limited case reports of pregnancy in females enrolled in clinical trials for TAZORAC Cream have not established a clear association with tazarotene and major birth defects or miscarriage risk. Because the exact timing and extent of exposure in relation to the gestational age are not certain, the significance of these findings is unknown. In animal reproduction studies with pregnant rats, tazarotene dosed topically during organogenesis at 2 times the maximum systemic exposure in subjects treated with the maximum recommended human dose (MRHD) of tazarotene cream, 0.1% resulted in reduced fetal body weights and reduced skeletal ossification.

In animal reproduction studies with pregnant rabbits dosed topically with tazarotene gel at 26 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1%, there was a single incident of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. In animal reproduction studies with pregnant rats and rabbits, tazarotene dosed orally during organogenesis at 2 and 52 times, respectively, the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1% resulted in malformations, fetal toxicity, developmental delays, and/or behavioral delays.

In pregnant rats, tazarotene dosed orally prior to mating through early gestation resulted in decreased litter size, decreased numbers of live fetuses, decreased fetal body weights, and increased malformations at doses approximately 7 times higher than the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1% [see Data ]. The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S.

general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and…