Overactive Bladder Prescribing Considerations: The Role of Polypharmacy, Anticholinergic Burden, and CYP2D6 Drug‒Drug Interactions

Abstract

Overactive bladder (OAB) is a common disorder in the general population, and the prevalence increases with age. Adults with OAB typically have a greater number of comorbid conditions, such as hypertension, depression, and dementia, compared with adults without OAB. Subsequent to an increased number of comorbidities, adults with OAB take a greater number of concomitant medications, which may increase the risk of potentially harmful drug‒drug interactions. There are two important considerations for many of the medications approved for the treatment of OAB in the USA: anticholinergic burden and potential for drug‒drug interactions, notably related to cytochrome P450 (CYP) 2D6, which is responsible for the metabolism of approximately 25% of all drugs. A substantial number of drugs used for the treatment of OAB and comorbid conditions (e.g., cardiovascular and neurologic disorders) are CYP2D6 substrates or inhibitors. Furthermore, a substantial number of drugs with CYP2D6 properties also have strong anticholinergic properties. Here, we review polypharmacy associated with OAB and its common comorbidities, identify drugs with reported anticholinergic properties, and provide an overview of clinically relevant drug‒drug interactions in the treatment of OAB as they relate to CYP2D6 metabolism. This review aims to provide clinicians with essential information necessary for making treatment decisions when managing OAB.

Utilization rate and long‐term persistence of combination pharmacotherapy with β3‐agonists and antimuscarinics for overactive bladder refractory to monotherapy in a real‐world setting

“…Although effective and well‐tolerated, combination therapy is not without drawbacks including concerns for anticholinergic burden, polypharmacy, and cytochrome P450 2D6 drug‐drug interactions 23 . Also it should be noted that 9.5% of the patients in the present study discontinued the treatment because of voiding impairment.…”

Implementation of Pharmacogenomics and Artificial Intelligence Tools for Chronic Disease Management in Primary Care Setting

“…The side effects table provides an emerging view of phenotypes that may have a pharmacologic root cause, based on First Data Bank side effects, and warrant further pharmacogenomic and pharmacokinetic analysis of a patient and their case. The combination of worsening symptoms and new medications in Patient’s A dashboard suggests that these symptoms may result from overburdening of the CYP2D6 pathway, an oxidative drug metabolizing pathway utilized by 25% of medications, and a common nexus for ADRs in polypharmacy [ 31 , 32 ]. This assessment is consistent with the finding that many of the medications taken by Patient A (duloxetine, tramadol, ondansetron, cyclobenzaprine, and olanzapine) interact with the CYP2D6 metabolic pathway.…”

“…Electronic health record alerts, computerized order entry systems, and pharmaceutical box warnings are insufficient in helping physicians at point of care to identify critical drug–drug or drug–gene interactions that might result from polypharmacy [ 31 ]. In this case, CYP1A2, CYP2D6, and CYP3A4 may be overburdened ( Figure 3 ) and perhaps overloaded to a point of significant clinical consequence.…”

Clinical Utility of β3-Adrenoreceptor Agonists for the Treatment of Overactive Bladder: A Review of the Evidence and Current Recommendations

“… 41 Additional use of AChs for OAB may lead to a significant increase in ACh load with an increased risk of cognitive impairment and dementia. 42 Other common ACh side effects, such as dry mouth, constipation, and QT prolongation, to which older people are particularly susceptible, should also be taken into consideration. Therefore, the use of mirabegron or other β 3 -ARAs may represent a valuable alternative to AChs in this vulnerable population.…”