Drug Interactions between Kemeya and treosulfan

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of drospirenone, which is partially metabolized by the isoenzyme. In a drug interaction study conducted in 20 premenopausal females, administration of a combined oral contraceptive containing drospirenone 3 mg and ethinyl estradiol 0.02 mg with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily) for 10 days increased drospirenone peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.97- and 2.68-fold, respectively, compared to administration of the contraceptive alone. When a single dose of the contraceptive was coadministered with atazanavir/cobicistat (300 mg/150 mg once daily) in 14 healthy study subjects, drospirenone Cmax was not altered but AUC increased by 2.30-fold. Administration of the contraceptive with another potent CYP450 3A4 inhibitor, boceprevir (800 mg three times daily for 7 days), increased Cmax and AUC of drospirenone by 57% and 99%, respectively. The interaction has not been studied with other, less potent CYP450 3A4 inhibitors. High exposure to drospirenone, a synthetic progestin and spironolactone analog, may potentiate the risk of hyperkalemia. When given at doses typically used for contraception, drospirenone has anti-mineralocorticoid activity comparable to a 25 mg dose of spironolactone.

MANAGEMENT: Caution and close clinical monitoring are recommended when drospirenone is prescribed with CYP450 3A4 inhibitors, particularly in patients requiring long-term concomitant use and those with other risk factors for hyperkalemia (e.g., renal insufficiency; coadministration with medications that can increase potassium such as aldosterone antagonists, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs (NSAIDs), potassium-sparing diuretics, potassium supplements, and heparin). Consider checking serum potassium levels during the first treatment cycle and periodically thereafter as indicated.