Drug Interactions between ethinyl estradiol / ethynodiol and troglitazone

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with troglitazone may decrease the plasma concentrations and efficacy of contraceptive hormones. The proposed mechanism is troglitazone induction of CYP450 3A4, the isoenzyme partially responsible for the metabolic clearance of sex hormones and other steroids. In 15 healthy female subjects, troglitazone (60 mg once daily for 3 weeks) decreased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ethinyl estradiol and norethindrone (35 mcg-1 mg) by approximately 30% each compared to administration of the contraceptive alone. Four subjects experienced breakthrough bleeding during the cycle with troglitazone.

MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with troglitazone. Alternative or additional methods of birth control should be used during and for at least two weeks after short-term and 4 weeks after long-term (greater than 4 weeks) troglitazone therapy. If a combination oral contraceptive pill is used, a regimen containing at least 50 mcg of ethinyl estradiol per day or equivalent should be selected. 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 levonorgestrel emergency contraception in patients receiving enzyme-inducing therapy, a regimen consisting of a 1.5 mg dose as soon as possible (within 72 hours of unprotected intercourse) followed by a 0.75 mg or 1.5 mg dose twelve hours later has been recommended by some clinicians. An alternative is a single 2.25 mg dose as soon as possible following unprotected intercourse. However, there are no data on efficacy, compliance, or side effects with any of these regimens. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action. Injectable progestin-only contraceptives are also thought to be unaffected by enzyme-inducing drugs.

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ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with troglitazone may decrease the plasma concentrations and efficacy of contraceptive hormones. The proposed mechanism is troglitazone induction of CYP450 3A4, the isoenzyme partially responsible for the metabolic clearance of sex hormones and other steroids. In 15 healthy female subjects, troglitazone (60 mg once daily for 3 weeks) decreased the mean steady-state peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ethinyl estradiol and norethindrone (35 mcg-1 mg) by approximately 30% each compared to administration of the contraceptive alone. Four subjects experienced breakthrough bleeding during the cycle with troglitazone.

MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with troglitazone. Alternative or additional methods of birth control should be used during and for at least two weeks after short-term and 4 weeks after long-term (greater than 4 weeks) troglitazone therapy. If a combination oral contraceptive pill is used, a regimen containing at least 50 mcg of ethinyl estradiol per day or equivalent should be selected. 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 levonorgestrel emergency contraception in patients receiving enzyme-inducing therapy, a regimen consisting of a 1.5 mg dose as soon as possible (within 72 hours of unprotected intercourse) followed by a 0.75 mg or 1.5 mg dose twelve hours later has been recommended by some clinicians. An alternative is a single 2.25 mg dose as soon as possible following unprotected intercourse. However, there are no data on efficacy, compliance, or side effects with any of these regimens. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action. Injectable progestin-only contraceptives are also thought to be unaffected by enzyme-inducing drugs.

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