CYP2D6 Substrate Dispensing Among Patients Dispensed Mirabegron: An Administrative Claims Analysis

Abstract

Background Overactive bladder (OAB) is characterized by the presence of bothersome urinary symptoms. Pharmacologic treatment options for OAB include anticholinergics and β 3 -adrenergic agonists. Use of β 3 -adrenergic agonists may result in similar treatment efficacy with a decreased side effect profile compared with anticholinergics because high anticholinergic burden is associated with cardiovascular and neurologic side effects. However, the β 3 -adrenergic agonist mirabegron, one of two approved drugs within this class, is a moderate cytochrome P450 (CYP) 2D6 inhibitor, and coadministration of drugs that are CYP2D6 substrates with mirabegron may lead to adverse drug effects. Objective The aim of this study was to quantify how often CYP2D6 substrates were dispensed in patients receiving mirabegron among adults of any age and among those ≥ 65 years of age. Methods In this retrospective descriptive analysis, a deidentified administrative claims database in the United States, IQVIA PharMetrics ® Plus, was used to identify dispensing claims for CYP2D6 substrates and mirabegron from November 2012 to September 2019. Prevalence of CYP2D6 substrate dispensing was assessed in patients dispensed mirabegron among all adults ≥ 18 years old and additionally among a cohort of those ≥ 65 years old. Patient baseline profiles at the time of mirabegron and CYP2D6 substrate codispensing and at the time of mirabegron dispensing were compared. CYP2D6 substrates were categorized as those with the potential for increased risk of QT prolongation, with anticholinergic properties, with narrow therapeutic index (NTI), contraindicated or having a black box warning when used with CYP2D6 inhibitors, or used for depression or other psychiatric disease. Dispensing data and patient profiles were summarized descriptively. Results Overall, 68.5% of adults ≥ 18 years old dispensed mirabegron had overlapping dispensings for one or more CYP2D6 substrate; 60.6% and 53.6% had overlapping dispensings for CYP2D6 substrates with anticholinergic properties or risk of QT prolongation, respectively. CYP2D6 substrates with NTI, contraindicated with CYP2D6 inhibitors, or for psychiatric use were codispensed in 17.7%, 16.6%, and 38.0% of adult mirabegron users, respectively. Mirabegron users receiving one or more concurrent CYP2D6 substrate were more likely to be older, have more comorbidities and baseline polypharmacy, and have increased healthcare resource utilization compared with those without concurrent CYP2D6 substrates. Commonly codispensed CYP2D6 substrates included hydrocodone, oxycodone, tramadol, metoprolol, and tamsulosin. Findings were similar for patients in the older cohort (≥ 65 years old), with 72.1% receiving overlapping CYP2D6 substrates. Conclusions Codispensing of CYP2D6 substrates, especially those w...

Assessment of Codispensing Patterns of Mirabegron and Prespecified CYP2D6 Substrates in Patients with Overactive Bladder

“…A previous analysis of dispensing claims has highlighted the high frequency with which CYP2D6 substrates of any kind are codispensed in patients with OAB receiving mirabegron; approximately 70% of patients who received mirabegron also received a CYP2D6 substrate [ 15 ]. Codispensing of ≥ 1 CYP2D6 substrate with mirabegron was associated with patients being older and with having increased healthcare resource utilization, baseline polypharmacy, and comorbidities compared with mirabegron users who did not receive concomitant CYP2D6 substrates [ 15 ]. In an analysis of medication dispensing in long-term care facilities, > 90% of residents who received mirabegron had also received a CYP2D6 substrate during a 5-year analysis window [ 17 ].…”

“…Mirabegron and ten predefined CYP2D6 substrate groups (amitriptyline/nortriptyline, aripiprazole, citalopram/escitalopram, donepezil, duloxetine/venlafaxine, hydrocodone, metoprolol/carvedilol, tamsulosin, tolterodine, and tramadol; Supplementary Table 1 in the electronic supplementary material [ESM]) were identified using National Drug Codes from pharmacy dispensing claims. Selection of CYP2D6 substrates was based on medications most frequently prescribed in the United States as defined previously [ 15 , 16 ], with high susceptibility to CYP2D6 inhibition, and with evidence for exposure-related toxicity that could result in an identifiable adverse effect. Medications were grouped together if they were in the same therapeutic class and were considered therapeutically interchangeable.…”

“…It is equally important to consider that CYP2D6 is responsible for at least partial metabolization of approximately 25% of the drugs in clinical use in the United States [ 14 ]. A previous claims database analysis showed high rates of codispensing of CYP2D6 substrates with mirabegron [ 15 ], suggesting a lack of awareness of this potential interaction.…”

Commentary on: Pharmacist‐driven interventions to de‐escalate urinary antimuscarinics in the Program of All‐Inclusive Care for the Elderly

“…A retrospective analysis of 106,260 commercially insured adult patients who were dispensed mirabegron between January 2011 and December 2019 found that 68.5% had overlapping dispensing with ≥1 CYP2D6 substrates. 9 Among patients ≥65 years of age, 72.1% had CYP2D6 substrate dispensations that overlapped with mirabegron. 9 A separate retrospective analysis of pharmacy claims from 159,785 residents in long-term care facilities who were dispensed OAB medications between May 1, 2013, and May 1, 2018, found that 93% of residents who received mirabegron were dispensed a CYP2D6 substrate during the analysis period.…”

“…9 Among patients ≥65 years of age, 72.1% had CYP2D6 substrate dispensations that overlapped with mirabegron. 9 A separate retrospective analysis of pharmacy claims from 159,785 residents in long-term care facilities who were dispensed OAB medications between May 1, 2013, and May 1, 2018, found that 93% of residents who received mirabegron were dispensed a CYP2D6 substrate during the analysis period. 10 Owing to study limitations, it is unknown if the CYP2D6 substrate dispensing overlapped with mirabegron dispensing, if residents took both the CYP2D6 substrate and mirabegron concurrently, or if prescribing clinicians made proactive dose adjustments to account for coadministration.…”