Drug Interaction Report

GENERALLY AVOID: Isotretinoin may decrease the plasma concentrations of contraceptive progestins. The potential mechanism of interaction has not been established. In a study of 26 healthy women receiving isotretinoin 1 mg/kg/day for severe, recalcitrant nodular acne and a contraceptive containing ethinyl estradiol and norethindrone for 2 cycles, the addition of isotretinoin resulted in small and inconsistent, but statistically significant decreases in the plasma concentrations of both contraceptive components. Specifically, mean ethinyl estradiol systemic exposure (AUC) decreased by 9% and norethindrone peak plasma concentration (Cmax) decreased by 11%. These changes were not associated with any statistically significant increases in pharmacodynamic markers of contraceptive effectiveness (concentrations of serum progesterone, luteinizing hormone, and follicle-stimulating hormone), although a majority of the subjects had increases in these measures. Given the substantial intersubject variability observed in both pharmacokinetic and pharmacodynamic measures, an interaction that decreases the effectiveness of contraceptive hormones cannot be ruled out. There have been reports of pregnancy occurring in female patients who have used combined oral contraceptives, as well as transdermal patch/injectable/implantable/vaginal ring hormonal birth control products. These reports were more frequent in female patients who used only a single method of contraception.

MANAGEMENT: The manufacturers caution that microdosed progesterone-only preparations ("minipills") may not be an adequate method of contraception during isotretinoin therapy and should not be used. Combination oral contraceptive pills are considered an acceptable primary form of contraception and may be used (please refer to the product labeling for list of acceptable primary and secondary forms of contraception). Due to the teratogenic risk of isotretinoin, females of reproductive potential must use two methods of effective contraception, at least one of which must be a primary form, for at least 1 month prior to initiation of isotretinoin therapy, during therapy, and for 1 month after discontinuing therapy.

GENERALLY AVOID: The combined use of ethanol and isotretinoin may result in a disulfiram-like reaction. The mechanism has not been established.

MANAGEMENT: Alcohol consumption should be avoided during isotretinoin therapy.