What medications or substances should be avoided when taking mirabegron (Beta-3 adrenergic agonist) to prevent interactions?

Drug and Alcohol Interactions with Mirabegron

Critical Drug Interactions Requiring Monitoring or Dose Adjustment

Mirabegron is a moderate CYP2D6 inhibitor and weak P-glycoprotein (P-gp) inhibitor, requiring careful attention when combined with drugs metabolized through these pathways. 1

CYP2D6 Substrate Medications (Require Monitoring)

When taking mirabegron with drugs metabolized by CYP2D6, especially those with narrow therapeutic indices, appropriate monitoring and possible dose adjustment are necessary. 1

Specific medications requiring caution include:

• Thioridazine (Mellaril) - specifically mentioned as requiring caution 1
• Flecainide (Tambocor) - specifically mentioned as requiring caution 1
• Propafenone (Rythmol) - specifically mentioned as requiring caution 1
• Metoprolol/Carvedilol - commonly codispensed with mirabegron for median duration of 75 days 2
• Duloxetine/Venlafaxine - commonly codispensed with mirabegron for median duration of 71 days 2
• Citalopram/Escitalopram - commonly codispensed with mirabegron for median duration of 62 days 2
• Tramadol - commonly codispensed with mirabegron for median duration of 15 days 2
• Hydrocodone - commonly codispensed with mirabegron for median duration of 9 days 2

Digoxin (Requires Specific Dosing Strategy)

When initiating mirabegron with digoxin, use the lowest dose of digoxin initially and monitor serum digoxin concentrations to titrate to desired clinical effect. 1 Mirabegron increases digoxin AUC and Cmax by 27% and 29%, respectively, due to P-gp inhibition 3. Patients require additional monitoring of digoxin concentrations with dose adjustments where necessary due to digoxin's narrow therapeutic index 3.

Strong CYP3A4 Inhibitors and Inducers

Ketoconazole (strong CYP3A4 inhibitor) increases mirabegron exposure by 81% (AUC) and 45% (Cmax), though dose adjustment is not routinely required. 4 However, caution is warranted when combining mirabegron with strong CYP3A4 inhibitors including itraconazole, posaconazole, and voriconazole 5.

Rifampicin (strong CYP3A4 inducer) decreases mirabegron exposure by 44% (AUC) and 35% (Cmax), potentially reducing efficacy. 4 Avoid combining mirabegron with strong CYP3A4 inducers when possible 4.

Medications with Additive Effects

Antimuscarinic Drugs for Overactive Bladder

Mirabegron has additive adverse effects, particularly cardiac disorders, when combined with antimuscarinic drugs. 6 However, combination therapy with solifenacin plus tamsulosin has been studied and can be used with appropriate monitoring 5.

Cardiovascular Medications

Exercise caution when combining mirabegron with medications that affect blood pressure or heart rate, as mirabegron can cause dose-dependent increases in blood pressure and cardiac arrhythmias, especially tachycardia. 6 This is particularly important in patients taking:

• Verapamil (moderate CYP3A4 and P-gp inhibitor) 5
• Diltiazem (moderate CYP3A4 inhibitor) 5
• Beta-blockers 5

Medications WITHOUT Significant Interactions

Mirabegron does not require dose adjustment when administered concomitantly with metformin, warfarin, or combined oral contraceptives (ethinylestradiol/levonorgestrel). 3 Specifically:

• Metformin: No clinically significant interaction, though metformin decreases mirabegron exposure by 21% 3
• Warfarin: No effect on warfarin pharmacokinetics or INR 3
• Oral contraceptives: No effect on ethinylestradiol or levonorgestrel pharmacokinetics 3

Alcohol Considerations

The FDA label does not specifically contraindicate alcohol use with mirabegron. 1 However, given mirabegron's potential to cause dizziness and the general recommendation to report all substances to healthcare providers, caution with alcohol is prudent 1.

Key Monitoring Recommendations

Advise patients to report their use of any prescription or nonprescription medications or dietary supplements because co-administration with mirabegron may require dose adjustment and/or increased monitoring. 1

Periodically monitor blood pressure, especially in hypertensive patients, as mirabegron can increase blood pressure. 1 Mirabegron is not recommended in patients with severe uncontrolled hypertension 1.

Common Pitfalls to Avoid

• Do not overlook CYP2D6 substrate medications - claims database analysis shows frequent overlapping exposure with medications like metoprolol, duloxetine, and tramadol 2
• Do not start digoxin at standard doses when initiating with mirabegron - always use the lowest digoxin dose and titrate based on serum levels 1, 3
• Do not assume all drug interactions are clinically significant - mirabegron is not considered a sensitive substrate of CYP3A in vivo, as ketoconazole increased exposure by less than 2-fold 4
• Do not forget to counsel patients about reporting all medications and supplements, as the interaction profile is complex 1