Drug Interactions between ethinyl estradiol / norelgestromin and mitotane

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with potent inducers of CYP450 3A4 may reduce the efficacy of contraceptive hormones as estrogens and progestins have been shown to be partially metabolized by CYP450 3A4. In a pharmacokinetic study of 28 healthy women, the systemic exposures (AUCs) of ethinyl estradiol and norethindrone decreased by 64% and 60%, respectively when coadministered with the potent CYP450 3A4 inducer rifampin.

MANAGEMENT: For patients receiving hormonal contraceptives, additional or alternative non-hormonal contraceptive methods may be advisable during concomitant therapy with potent CYP450 3A4 inducers and patients should be advised of the risk of breakthrough bleeding and unintended pregnancy. Additional or alternative non-hormonal contraceptive methods may be recommended beyond discontinuation of the CYP450 3A4 inducer(s). Individual product labeling should be consulted for specific time frames. Although breakthrough bleeding is not necessarily indicative of low ethinyl estradiol serum levels or increased risk of ovulation, some clinicians suggest that women who experience breakthrough bleeding during enzyme-inducing therapy may be prescribed an increased dose of ethinyl estradiol above 50 mcg daily by combining more than one formulation of contraceptive pill if necessary. For emergency contraception in patients who have used an hepatic enzyme inducer in the past 4 weeks, a non-hormonal emergency contraceptive (e.g., copper intrauterine device) is considered preferable. If this is not possible, some authorities recommend that the usual dose of levonorgestrel (1.5 mg) should be doubled to 3 mg and taken as a single dose as soon as possible (within 72 hours of unprotected sexual intercourse). However, there are no data on efficacy, compliance, or side effects of this regimen. Intrauterine systems are unlikely to be significantly affected because of their local action. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed.

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with potent inducers of CYP450 3A4 may reduce the efficacy of contraceptive hormones as estrogens and progestins have been shown to be partially metabolized by CYP450 3A4. In a pharmacokinetic study of 28 healthy women, the systemic exposures (AUCs) of ethinyl estradiol and norethindrone decreased by 64% and 60%, respectively when coadministered with the potent CYP450 3A4 inducer rifampin.

MANAGEMENT: For patients receiving hormonal contraceptives, additional or alternative non-hormonal contraceptive methods may be advisable during concomitant therapy with potent CYP450 3A4 inducers and patients should be advised of the risk of breakthrough bleeding and unintended pregnancy. Additional or alternative non-hormonal contraceptive methods may be recommended beyond discontinuation of the CYP450 3A4 inducer(s). Individual product labeling should be consulted for specific time frames. Although breakthrough bleeding is not necessarily indicative of low ethinyl estradiol serum levels or increased risk of ovulation, some clinicians suggest that women who experience breakthrough bleeding during enzyme-inducing therapy may be prescribed an increased dose of ethinyl estradiol above 50 mcg daily by combining more than one formulation of contraceptive pill if necessary. For emergency contraception in patients who have used an hepatic enzyme inducer in the past 4 weeks, a non-hormonal emergency contraceptive (e.g., copper intrauterine device) is considered preferable. If this is not possible, some authorities recommend that the usual dose of levonorgestrel (1.5 mg) should be doubled to 3 mg and taken as a single dose as soon as possible (within 72 hours of unprotected sexual intercourse). However, there are no data on efficacy, compliance, or side effects of this regimen. Intrauterine systems are unlikely to be significantly affected because of their local action. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed.