Drug Interaction Report

MONITOR: Coadministration of inhaled ciclesonide with potent inhibitors of CYP450 3A4 may increase systemic bioavailability of the pharmacologically active metabolite, des-ciclesonide, which is a substrate of the isoenzyme. In one study, administration of orally inhaled ciclesonide in combination with the potent inhibitor ketoconazole resulted in an approximately 3.6-fold increase in steady-state des-ciclesonide systemic exposure (AUC), while levels of ciclesonide remained unchanged. In another study, coadministration of orally inhaled ciclesonide with erythromycin, a less potent inhibitor, had no effect on the pharmacokinetics of des-ciclesonide.

MANAGEMENT: Caution is advised if ciclesonide is prescribed with potent CYP450 3A4 inhibitors. 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 systemic glucocorticoid effects including symptoms of hypercorticism (e.g., acne, easy bruising, moon face, edema, hirsutism, buffalo hump, skin striae, irregular menstruations), adrenal suppression (which reduces patient's ability to respond to stress situations), immunosuppression, osteoporosis, glucose intolerance, and exacerbation of diabetes mellitus.

GENERALLY AVOID: Taking stiripentol on an empty stomach may reduce its oral bioavailability. Stiripentol degrades rapidly when exposed to gastric acid in an empty stomach.

GENERALLY AVOID: Alcohol may potentiate the depressant effects of stiripentol on the central nervous system. Concomitant use may result in increased sedation and dizziness as well as impairment of psychomotor skills.

GENERALLY AVOID: It is not known whether stiripentol may reduce theophylline and caffeine metabolism, as data on the potential for inhibition of CYP450 1A2 are limited. Consumption of foods and nutritional products such as cola drinks (which contain significant quantities of caffeine) and chocolate (which contains caffeine and trace amounts of theophylline) may be unsafe during treatment with stiripentol, particularly in children.

MANAGEMENT: Stiripentol should be taken during a meal for optimal absorption; however, it should not be taken with milk, dairy products (e.g., yogurt, soft cream cheese), fruit juice, or carbonated beverages. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them. Food and beverages that may contain caffeine or theophylline such as colas, chocolate, coffee, tea, or energy drinks should also be avoided during treatment with stiripentol.