Drug Interactions between conivaptan and mometasone

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of mometasone, which is primarily metabolized by the isoenzyme. In healthy subjects coadministered mometasone (400 mcg inhaled twice daily for 9 days) with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally twice daily on days 4 to 9), 4 out of 12 subjects had peak plasma concentrations of mometasone increase from less than 150 pcg/mL on day 3 before the addition of ketoconazole to more than 200 pcg/mL afterwards. Serum cortisol AUC also decreased slightly after ketoconazole was added. The clinical significance of these findings is unknown.

MANAGEMENT: The possibility of increased systemic adverse effects of mometasone should be considered during coadministration with potent CYP450 3A4 inhibitors. Some authorities advise against concomitant use unless the potential benefit outweighs the risk. If the combination cannot be avoided, the dosing times between mometasone and the CYP450 3A4 inhibitor should be separated by as much as possible. In addition, the lowest effective dosage of mometasone should be prescribed, and further adjustments made as necessary according to therapeutic response and tolerance. Alternatively, a less potent, less lipophilic, and/or shorter-acting agent such as beclomethasone may be considered. Beclomethasone is also less dependent on CYP450 3A4 metabolism. Patients should be monitored for signs and symptoms of hypercorticism such as acne, striae, thinning of the skin, easy bruising, moon facies, dorsocervical "buffalo" hump, truncal obesity, increased appetite, acute weight gain, edema, hypertension, hirsutism, hyperhidrosis, proximal muscle wasting and weakness, glucose intolerance, exacerbation of preexisting diabetes, depression, and menstrual disorders. Other systemic glucocorticoid effects may include adrenal suppression, immunosuppression, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents.