Drug Interactions between Dalalone DP and Incivek

GENERALLY AVOID: Coadministration with dexamethasone may decrease the plasma concentrations of the hepatitis C virus NS3/4A protease inhibitors, boceprevir and telaprevir. The proposed mechanism is dexamethasone induction of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of these and other protease inhibitors. The interaction has not been specifically studied with dexamethasone, but has been reported with the potent CYP450 3A4 inducer, rifampin. In 16 study subjects, administration of a single 750 mg dose of telaprevir during treatment with rifampin 600 mg daily for 7 days reduced the telaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 86% and 92%, respectively, compared to administration alone. Conversely, boceprevir and telaprevir are potent inhibitors of CYP450 3A4 and may theoretically increase the plasma concentrations of dexamethasone, which is a substrate of the isoenzyme.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic drug levels, concomitant use of boceprevir or telaprevir with dexamethasone should be avoided if possible. Otherwise, close clinical monitoring of the virologic response is advised. In addition, patients may experience increased systemic glucocorticoid effects and 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, and bone loss. Dosage reduction for dexamethasone may be required.

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