Drug Interaction Report

ADJUST DOSE: Coadministration with drugs that are inhibitors of CYP450 3A4 may increase the plasma concentrations of tolterodine, which is partially metabolized by the isoenzyme. The possibility of prolonged and/or increased pharmacologic effects of tolterodine should be considered. Although tolterodine is primarily metabolized by CYP450 2D6, there is some evidence that CYP450 3A4 may play a minor role, thus any alteration in its activity levels could conceivably affect the metabolism of tolterodine. The clinical significance of this interaction is yet unknown but may be greater in patients who are CYP450 2D6-deficient, or so-called poor metabolizers of CYP450 2D6 (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent).

MANAGEMENT: The manufacturer recommends a maximum tolterodine dosage of 1 mg twice daily in patients receiving concomitant CYP450 3A4 inhibitors. Close clinical and laboratory monitoring is advised whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. Patients should be advised to notify their physician if they experience an irregular heartbeat, severe blurry vision, difficulty urinating, dry mouth, headache, drowsiness, dizziness, or GI upset.

ADJUST DOSE: Coadministration with drugs that are inhibitors of CYP450 3A4 may increase the plasma concentrations of tolterodine, which is partially metabolized by the isoenzyme. The possibility of prolonged and/or increased pharmacologic effects of tolterodine should be considered. Although tolterodine is primarily metabolized by CYP450 2D6, there is some evidence that CYP450 3A4 may play a minor role, thus any alteration in its activity levels could conceivably affect the metabolism of tolterodine. The clinical significance of this interaction is yet unknown but may be greater in patients who are CYP450 2D6-deficient, or so-called poor metabolizers of CYP450 2D6 (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent).

MANAGEMENT: The manufacturer recommends a maximum tolterodine dosage of 1 mg twice daily in patients receiving concomitant CYP450 3A4 inhibitors. Close clinical and laboratory monitoring is advised whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. Patients should be advised to notify their physician if they experience an irregular heartbeat, severe blurry vision, difficulty urinating, dry mouth, headache, drowsiness, dizziness, or GI upset.

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.