Detrusitol SR Drug Interactions

Potent CYP2D6 Inhibitors: Fluoxetine, a potent inhibitor of CYP2D6 activity, significantly inhibited the metabolism of tolterodine immediate release in CYP2D6 extensive metabolizers, resulting in a 4.8-fold increase in tolterodine AUC. There was a 52% decrease in C_max and a 20% decrease in AUC of 5-hydroxymethyl tolterodine (5-HMT), the pharmacologically active metabolite of tolterodine [see PHARMACOLOGY under Actions]. The sums of unbound serum concentrations of tolterodine and 5-HMT are only 25% higher during the interaction. No dose adjustment is required when tolterodine and fluoxetine are co-administered [see PHARMACOLOGY under Actions].
Potent CYP3A4 Inhibitors: Ketoconazole (200 mg daily), a potent CYP3A4 inhibitor, increased the mean C_max and AUC of tolterodine by 2- and 2.5-fold, respectively in CYP2D6 poor metabolizers.
For patients receiving ketoconazole or other potent CYP3A4 inhibitors such as itraconazole, clarithromycin or ritonavir, the recommended dose of DETRUSITOL SR is 2 mg once daily [see DOSAGE & ADMINISTRATION and PHARMACOLOGY under Actions].
Other Interactions: No clinically relevant interactions have been observed when tolterodine was co-administered with warfarin, with a combined oral contraceptive drug containing ethinyl estradiol and levonorgestrel, or with diuretics [see PHARMACOLOGY under Actions.]
Other Drugs Metabolized by Cytochrome P450 Isoenzymes: In vivo drug-interaction data show that tolterodine immediate release does not result in clinically relevant inhibition of CYP1A2, 2D6, 2C9, 2C19, or 3A4 as evidenced by lack of influence on the marker drugs caffeine, debrisoquine, S-warfarin, and omeprazole [see PHARMACOLOGY under Actions].
Drug-laboratory Test Interactions: Interactions between tolterodine and laboratory tests have not been studied.
Other Anticholinergics: The concomitant use of DETRUSITOL SR with other anticholinergic (antimuscarinic) agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision, somnolence and other anticholinergic pharmacological effects.