Evaluation of drug-drug interactions with fesoterodine.
Article Details
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Malhotra B, Sachse R, Wood N
Evaluation of drug-drug interactions with fesoterodine.
Eur J Clin Pharmacol. 2009 Jun;65(6):551-60. doi: 10.1007/s00228-009-0648-1. Epub 2009 Apr 4.
- PubMed ID
- 19347334 [ View in PubMed]
- Abstract
PURPOSE: To assess drug-drug interactions of fesoterodine with cytochrome P450 (CYP) 3A4 inhibitor (ketoconazole), inducer (rifampicin), and substrates (ethinylestradiol and levonorgestrel). METHODS: Effects of ketoconazole 200 mg twice daily and rifampicin 600 mg twice daily on fesoterodine 8 mg once daily were investigated in CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs) based on 5-hydroxymethyl tolterodine (5-HMT) pharmacokinetics (principal active fesoterodine metabolite and CYP3A4 substrate). Effects of fesoterodine 8 mg versus placebo once daily on ethinylestradiol and levonorgestrel were investigated based on oral contraceptive pharmacokinetics and on pharmacodynamic effects on progesterone, luteinizing hormone, follicle-stimulating hormone, and estradiol plasma levels. RESULTS: Compared with fesoterodine alone, coadministration of fesoterodine with ketoconazole resulted in increases in mean 5-HMT maximum concentration in plasma (C(max); from 3.0 to 6.0 ng/mL in EMs and from 6.4 to 13.4 ng/mL in PMs) and mean area under the plasma concentration time curve (AUC; from 38.2 to 88.3 ng h/mL in EMs and 88.3 to 217.2 ng h/mL in PMs). Coadministration of festerodine with rifampicin resulted in decreases in mean 5-HMT C(max) (from 5.2 to 1.5 ng/mL in EMs and from 6.8 to 1.9 ng/mL in PMs) and mean AUC (from 62.4 to 14.4 ng h/mL in EMs and from 87.8 to 19.6 ng h/mL in PMs). Fesoterodine did not affect oral contraceptive pharmacokinetics or pharmacodynamics or the suppression of ovulation. CONCLUSIONS: 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Fesoterodine Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails Fesoterodine Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareFesoterodineMethimazole The metabolism of Fesoterodine can be decreased when combined with Methimazole. FesoterodineMidostaurin The metabolism of Fesoterodine can be decreased when combined with Midostaurin. FesoterodineRitonavir The metabolism of Fesoterodine can be decreased when combined with Ritonavir. FesoterodineVoriconazole The metabolism of Fesoterodine can be decreased when combined with Voriconazole. FesoterodineEfavirenz The metabolism of Fesoterodine can be decreased when combined with Efavirenz.