DRUG INTERACTIONS
Changes in Contraceptive Effectiveness Associated With Co-Administration of Other Drugs
Contraceptive effectiveness may be reduced when hormonal contraceptives are co-administered with some antibiotics, antifungals, anticonvulsants, and other drugs that increase metabolism of contraceptive steroids. This could result in unintended pregnancy or breakthrough bleeding. Examples include barbiturates, griseofulvin, rifampin, phenylbutazone, phenytoin, carbamazepine, felbamate, oxcarbazepine, topiramate and possibly with ampicillin.
The proposed mechanism of interaction of antibiotics is different from that of liver enzyme-inducing drugs. Literature suggests possible interactions with the concomitant use of hormonal contraceptives and ampicillinor tetracycline. In a pharmacokinetic drug interaction study, oral administration of tetracycline HCl, 500 mg q.i.d. for 3 days prior to and 7 days during wear of ORTHO EVRA® did not significantly affect the pharmacokinetics of norelgestromin or EE.
Several of the anti-HIV protease inhibitors have been studied with co-administration of oral combination hormonal contraceptives; significant changes (increase and decrease) in the mean AUC of the estrogen and progestin have been noted in some cases. The efficacy and safety of oral contraceptive products may be affected; it is unknown whether this applies to ORTHO EVRA®. Healthcare professionals should refer to the label of the individual anti-HIV protease inhibitors for further drug-drug interaction information.
Herbal products containing St. John's Wort (hypericum perforatum) may induce hepatic enzymes (cytochrome P450) and p-glycoprotein transporter and may reduce the effectiveness of contraceptive steroids. This may also result in breakthrough bleeding.
Increase in Plasma Hormone Levels Associated With Co-Administered Drugs
Co-administration of atorvastatin and certain oral contraceptives containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol levels, possibly by inhibition of conjugation. CYP 3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels.
Changes in Plasma Levels of Co-Administered Drugs
Combination hormonal contraceptives containing some synthetic estrogens (e.g., ethinyl estradiol) may inhibit the metabolism of other compounds. Increased plasma concentrations of cyclosporine, prednisolone, and theophylline have been reported with concomitant administration of oral contraceptives. In addition, oral contraceptives may induce the conjugation of other compounds. Decreased plasma concentrations of acetaminophen and increased clearance of temazepam, salicylic acid, morphine and clofibric acid have been noted when these drugs were administered with oral contraceptives.
Although norelgestromin and its metabolites inhibit a variety of P450 enzymes in human liver microsomes, the clinical consequence of such an interaction on the levels of other concomitant medications is likely to be insignificant. Under the recommended dosing regimen, the in vivo concentrations of norelgestromin and its metabolites, even at the peak serum levels, are relatively low compared to the inhibitory constant (Ki) (based on results of in vitro studies).
Combined hormonal contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine when co-administered due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary.
Health care professionals are advised to also refer to prescribing information of co-administered drugs for recommendations regarding management of concomitant therapy.
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