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Key Points
Concomitant use of drugs that are cytochrome P450 (CYP2D6) substrates with drugs that inhibit CYP2D6 may result in unintended increases in concentration of the substrate, potentially increasing the risk of drug–drug interactions. |
Patients with overactive bladder often have comorbidities, and therefore the rate of polypharmacy and subsequent use of CYP2D6 substrates is high. |
Patients receiving mirabegron, a moderate CYP2D6 inhibitor approved for the treatment of overactive bladder, showed substantial overlapping days of codispensing with CYP2D6 substrates, with ≥ 60 days of overlap frequently identified. |
Introduction
Overactive bladder (OAB) is a chronic disorder characterized by bothersome urinary symptoms in which patients experience sudden and intense urges to urinate, which may be associated with urge urinary incontinence or nocturia [1]. OAB prevalence in the United States is 16.5% for adults ≥ 18 years old, and this rate increases with age [2]. Patients with OAB often have comorbidities. Among patients with OAB, prevalence of any cardiovascular comorbidity has been reported as 57.6% versus 44.6% for patients without OAB [3]; prevalence of depression in patients with OAB has been shown to be 10.7% versus 4.7% in patients without OAB [4]. When combined with multiple medications across multiple indications, these comorbidities can lead to increased risk of drug‒drug interactions (DDIs). Rates of polypharmacy, defined as use of ≥ 5 concurrent medications, is seen in nearly 40% of patients with OAB [5].
First-line treatment in OAB management involves behavioral therapy through bladder training, pelvic floor muscle training, and fluid management with or without pharmacotherapy. Pharmacologic treatment includes anticholinergics and/or β3-adrenergic receptor agonists [1]. American Urological Association and American Geriatrics Society guidelines recommend reducing anticholinergic use in older adults to minimize anticholinergic burden [1, 6], which is associated with increased risk of cognitive impairment and dementia [7, 8]. β3-adrenergic receptor agonists are recommended in patients who are using other medications with anticholinergic properties for comorbidities and have been shown to be as efficacious as anticholinergic therapies without adding to anticholinergic burden [9].
Mirabegron, a β3-adrenergic receptor agonist, is used in the management of OAB in conjunction with or as a replacement for anticholinergic therapy. Mirabegron has a label warning for moderate inhibitory effects on cytochrome P450 (CYP) 2D6 [10]. Moderate CYP2D6 inhibitor coadministration with...