Drug Interactions between ethinyl estradiol / norelgestromin and nelfinavir

ADDITIONAL CONTRACEPTION RECOMMENDED: Nelfinavir may decrease the plasma concentrations of contraceptive hormones during chronic coadministration. The proposed mechanism is nelfinavir induction of the hepatic metabolism of sex hormones. In 12 study subjects, nelfinavir (750 mg every 8 hours for 7 days) decreased the mean peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of ethinyl estradiol (administered as ethinyl estradiol-norethindrone 0.035 mg-0.4 mg once a day for 15 days) by 28%, 47% and 62%, respectively, compared to administration of the oral contraceptive alone. The mean AUC and Cmin of norethindrone decreased by 18% and 46%, respectively.

MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with nelfinavir. Alternative or additional methods of birth control should be used during and for at least 4 weeks after nelfinavir 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 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.
-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.

ADDITIONAL CONTRACEPTION RECOMMENDED: Nelfinavir may decrease the plasma concentrations of contraceptive hormones during chronic coadministration. The proposed mechanism is nelfinavir induction of the hepatic metabolism of sex hormones. In 12 study subjects, nelfinavir (750 mg every 8 hours for 7 days) decreased the mean peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of ethinyl estradiol (administered as ethinyl estradiol-norethindrone 0.035 mg-0.4 mg once a day for 15 days) by 28%, 47% and 62%, respectively, compared to administration of the oral contraceptive alone. The mean AUC and Cmin of norethindrone decreased by 18% and 46%, respectively.

MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with nelfinavir. Alternative or additional methods of birth control should be used during and for at least 4 weeks after nelfinavir 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 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.
-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.