Drug Interactions between celecoxib / tramadol and fesoterodine

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.

MONITOR: Coadministration of opioids with anticholinergic agents may result in additive central nervous system (CNS), gastrointestinal, and genitourinary effects. The risk and/or severity of adverse effects such as sedation, dizziness, confusion, cognitive and psychomotor impairment, dry mouth, constipation, and urinary retention may increase. Severe constipation may lead to paralytic ileus in some cases.

MANAGEMENT: Caution and close monitoring of central nervous system, gastrointestinal, and genitourinary adverse effects are recommended when opioids are used with anticholinergic agents. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations of fesoterodine's active metabolite, 5-hydroxymethyl tolterodine, which is partially metabolized by the isoenzyme. The interaction has not been examined in pharmacokinetic studies. In poor metabolizers of CYP450 2D6, representing maximum CYP450 2D6 inhibition, 5-hydroxymethyl tolterodine peak plasma concentration (Cmax) and systemic exposure (AUC) are increased 1.7- and 2-fold, respectively, relative to extensive metabolizers.

MANAGEMENT: No initial dosing adjustments are recommended when fesoterodine is used in combination with CYP450 2D6 inhibitors. Patients should be advised to notify their physician if they experience potential adverse effects of fesoterodine such as irregular heartbeat, blurry vision, difficulty urinating, dry mouth, headache, drowsiness, dizziness, gastrointestinal upset, or constipation.