Drug interactions between CombiPatch and griseofulvin

ADDITIONAL CONTRACEPTION RECOMMENDED: Limited clinical data suggest that griseofulvin may reduce the efficacy of contraceptive hormones. There have been case reports of menstrual abnormalities (e.g., breakthrough bleeding, amenorrhea, irregular menses) or unintended pregnancy following the addition of griseofulvin in patients receiving long-term oral contraceptives. The proposed mechanism is accelerated clearance of the hormones due to induction of hepatic CYP450 enzymes by griseofulvin.

MANAGEMENT: Women using low-dose hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with griseofulvin. Because griseofulvin has been shown to be teratogenic in animal studies and is capable of inducing aneuploidy (abnormal segregation of chromosomes following cell division) in mammalian cells in vitro and in vivo, it is particularly important that patients not become pregnant during treatment. Therefore, additional methods of birth control should be used during and for one month after griseofulvin therapy. Input from a gynecologist or similar expert on adequate contraception should be sought as needed. Intrauterine systems are unlikely to be significantly affected because of their local action.

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of estrogens and progestins. Estrogens have been shown in in vitro and in vivo studies to be partially metabolized by CYP450 3A4, and other steroids including progestins are also believed to undergo metabolism by this isoenzyme. The interaction has been reported primarily with oral contraceptives. There have been case reports of menstrual breakthrough bleeding or unwanted pregnancy in women receiving low-dose oral contraceptives following the addition of known CYP450 3A4 inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort. Inadequate response to estrogen replacement therapy has also been reported in a patient treated with phenytoin. Aminoglutethimide, a CYP450 3A4 inducer, has been shown to decrease medroxyprogesterone and megestrol serum levels by 74% in six patients stabilized on their progestin regimen.

MANAGEMENT: Pharmacologic response to estrogens and progestins should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the hormone dosage adjusted as necessary. Patients should be advised to notify their physician if they experience inadequate control of symptoms associated with estrogen deficiency (e.g., nocturnal sweating, vasomotor disturbances, atrophic vaginitis) or changes in the uterine bleeding profile.