Evaluation of drug–drug interactions with fesoterodine

Abstract

Fesoterodine dosage should not exceed 4 mg once daily when taken concomitantly with potent CYP3A4 inhibitors. Coadministration of CYP3A4 inducers with fesoterodine may produce subtherapeutic 5-HMT exposures. No dose adjustment is necessary for concomitant use of fesoterodine with oral contraceptives.

Fesoterodine clinical efficacy and safety for the treatment of overactive bladder in relation to patient profiles: a systematic review

“…The key results of the 15 retained articles [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] on the pharmacology of oral fesoterodine are summarized in Table 1. After single or multiple dosing of oral fesoterodine 4 mg to 28 mg once daily, plasma concentrations of the active metabolite 5-HMT are proportional to the dose 16,17 .…”

“…In CYP2D6 poor metabolizers (PMs), the mean C max and AUC of 5-HMT are approximately two-fold higher than in CYP2D6 extensive metabolizers (EMs) 16,17,19 ; no fesoterodine dosing adjustment is recommended in the presence of CYP2D6 inhibitors 12 . The terminal half-life (t ½ ) of 5-HMT is approximately 7 to 9 hours after fesoterodine oral dosing 16,18,20 . In healthy adults treated with fesoterodine, variability in exposure to 5-HMT is relatively low and dose related 17 .…”

Can we predict which patient will fail drug treatment for overactive bladder? A think tank discussion

“…This can be altered in patients with genetic polymorphism affecting activity of key enzymes (e.g., ∼7% of the Caucasian population are poor metabolizers for cytochrome P450 [CYP] 2D6, which is involved in metabolism of many antimuscarinics). 33 It can also be affected by hepatic impairment 34 or concomitant administration of others drugs that inhibit relevant enzymes [e.g., ketoconazole inhibits activity of CYP 3A4, significantly increasing plasma levels of some antimuscarinics 35−37 , or induce activity of these enzymes [e.g., rifampicin induces CYP 3A4, resulting in reduced plasma levels of antimuscarinics 35 ; (iv) Elimination may be affected by renal impairment-indeed renal impairment causes an increase in plasma levels of some antimuscarinics more than fourfold 31 ; (v) Drug-drug interactions-concomitant administration of antimuscarinic medications with another drugs may cause variation in the drug exposure (area under the curve) and the maximum serum drug concentration (C max ). 35 Many of the factors are systematically evaluated during drug development and are clearly described in product labeling.…”

Role of fesoterodine in the treatment of overactive bladder

“…39 Breakdown of 5-HMT, generated from either tolterodine or fesoterodine, to inactive metabolites occurs via cytochrome P450 3A4 and CYP2D6 ( Figure 1) and is therefore varied in extensive and poor metabolizers. 45,46 Approximately 70% of the fesoterodine dose is eliminated via the urine with approximately 16% being eliminated as 5-HMT 42 the rest as inactive metabolites. 43 The urine elimination of 5-HMT increasing proportionally with fesoterodine dose.…”