Drug Interactions between nefazodone and tamsulosin

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of tamsulosin, which is primarily metabolized by the hepatic microsomal isoenzymes CYP450 3A4 and 2D6. Severe hypotension and priapism may occur. In 24 healthy volunteers, administration of a single 0.4 mg dose of tamsulosin with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily for 5 days) resulted in a 2.2-fold increase in tamsulosin peak plasma concentration (Cmax) and 2.8-fold increase in systemic exposure (AUC). The magnitude of interaction may be increased further in individuals who have genetic polymorphisms of CYP450 2D6 resulting in reduced or absent enzyme activity, or so-called CYP450 2D6 poor metabolizers (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent). When a single 0.4 mg dose of tamsulosin was given to 24 healthy volunteers with the potent CYP450 2D6 inhibitor paroxetine (20 mg once daily for 9 days), tamsulosin Cmax and AUC increased by a factor of 1.3 and 1.6, respectively. A similar increase in exposure is expected in CYP450 2D6 poor metabolizers as compared to extensive metabolizers, hence a potentially greater impact of CYP450 3A4 inhibition.

MANAGEMENT: Since CYP450 2D6 poor metabolizers cannot be readily identified, concomitant use of tamsulosin with potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of tamsulosin during and for 2 weeks after treatment with itraconazole. If tamsulosin administration is discontinued for several days or more at either the 0.4 or 0.8 mg dose, therapy should be reinitiated with the 0.4 mg once-daily dose and titrated gradually as needed.

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