Drug Interactions between drospirenone and Omeclamox-Pak

MONITOR CLOSELY: Coadministration with potent inhibitors of CYP450 3A4 may significantly 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. 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 potent 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. Due to the risk for hyperkalemia, concomitant use with certain CYP450 3A4 inhibitors such as boceprevir or cobicistat-boosted atazanavir is considered contraindicated by the manufacturers.

Switch to consumer interaction data

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

Switch to consumer interaction data

Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.

Switch to consumer interaction data