Interactions between cycrin(medroxyPROGESTERone) and Clopine (clozapine)
clozapine and medroxyPROGESTERone (Moderate Drug-Drug)
MONITOR: Limited data suggest that coadministration with contraceptive hormones may increase the plasma concentrations of clozapine. The exact mechanism of interaction is unknown but may involve inhibition of clozapine metabolism via CYP450 1A2, 2C19 and/or 3A4. A case report describes a 47-year-old woman with refractory paranoid schizophrenia who experienced drowsiness, weakness, and dizziness in association with elevated clozapine plasma levels (736, 770, and 792 ng/mL) during the first 2 months of clozapine therapy while she was also receiving long-term ethinyl estradiol-norethindrone (0.035 mg-0.5 mg) contraception. When the oral contraceptive was discontinued, the patient reported resolution of the clozapine side effects within days. A clozapine level obtained 1 week after contraceptive discontinuation was 401 ng/mL, and two subsequent blood levels over the next 6 weeks showed stable levels of 378 and 389 ng/mL. Although the patient was a heavy smoker, which may have affected the pharmacokinetics of clozapine, no change in her smoking habit was observed during this period.
MANAGEMENT: Patients treated concomitantly with hormonal contraceptives may require a lower dosage of clozapine to control psychotic symptoms. Pharmacologic response to clozapine should be monitored more closely whenever an oral contraceptive is added to or withdrawn from therapy in patients stabilized on their existing antipsychotic regimen, and the clozapine dosage adjusted as necessary.
