Is Myrbetriq (Mirabegron) contraindicated with Digoxin in patients, especially the elderly or those with a history of heart conditions?

Is Myrbetriq Contraindicated with Digoxin?

No, Myrbetriq (mirabegron) is not contraindicated with digoxin, but this combination requires careful monitoring because mirabegron can increase digoxin levels through P-glycoprotein inhibition, particularly in elderly patients or those with cardiac conditions.

Mechanism of Interaction

• Mirabegron inhibits P-glycoprotein, the same transport protein responsible for digoxin elimination, which can elevate serum digoxin concentrations and increase toxicity risk even when levels remain within the therapeutic range 1
• This interaction parallels other P-glycoprotein inhibitors like macrolides and cardiovascular drugs (especially amiodarone) that are known to cause digoxin overdose through the same mechanism 1

Risk Stratification for Elderly and Cardiac Patients

High-risk patients requiring heightened vigilance include:

• Patients over 70 years of age, who have significantly prolonged digoxin half-life (69.6 hours vs 36.8 hours in younger patients) and reduced total-body clearance 2
• Those with renal impairment, as digoxin elimination is primarily renal and elderly patients often have diminished renal function even with normal serum creatinine 3, 4
• Patients with low lean body mass, which increases digoxin sensitivity 3
• Those with pre-existing electrolyte disturbances (hypokalemia, hypomagnesemia, hypercalcemia), as these conditions potentiate digoxin toxicity even at therapeutic serum levels 5, 1
• Patients with heart failure and reduced ejection fraction (LVEF <40%), who are already at higher baseline risk for arrhythmias 3

Required Monitoring Protocol

Before initiating mirabegron in a patient on digoxin:

• Check baseline digoxin level (target therapeutic range: 0.5-0.9 ng/mL for heart failure, 0.6-1.2 ng/mL for atrial fibrillation) 3, 6
• Verify serum potassium is 4.0-5.5 mEq/L and correct any hypokalemia or hypomagnesemia before proceeding 3, 5
• Assess renal function using creatinine clearance, not just serum creatinine, especially in elderly patients 3, 4

After starting mirabegron:

• Recheck digoxin level 5-7 days after initiating mirabegron in patients with normal renal function, or 2-3 weeks in those with renal impairment 3
• Monitor continuously for early warning signs of digoxin toxicity: bradycardia (heart rate <60 bpm), gastrointestinal symptoms (anorexia, nausea, vomiting), and neurological symptoms (confusion, visual disturbances including yellow vision) 5, 1, 7
• Serial monitoring of serum electrolytes (especially potassium and magnesium) is mandatory, as digoxin can cause arrhythmias particularly with hypokalemia 3, 5

Dose Adjustment Strategy

If digoxin levels increase or approach the upper therapeutic range:

• Consider empirically reducing digoxin dose by 25-50% when initiating mirabegron, particularly in patients with additional risk factors (age >70, renal impairment, low lean body mass) 5
• For elderly patients already on digoxin 0.125 mg daily, consider reducing to 0.125 mg every other day or 0.0625 mg daily 3, 6
• Target the lower end of the therapeutic range (0.5-0.7 ng/mL) rather than higher concentrations, as levels above 1.0 ng/mL offer no additional benefit and may increase mortality risk 3, 6

Cardiac Arrhythmia Monitoring

Watch specifically for digoxin-induced arrhythmias:

• Enhanced atrial, junctional, or ventricular automaticity (ectopic beats) often combined with atrioventricular block 5
• Ventricular tachycardia that is fascicular or bidirectional in origin, which is highly suggestive of digoxin toxicity 5
• New-onset bradycardia, sinoatrial block, or second/third-degree AV block 3, 5

Absolute Contraindications to Consider

Do not use this combination if the patient has:

• Second- or third-degree heart block without a permanent pacemaker 3, 6
• Pre-excitation syndromes (Wolff-Parkinson-White syndrome with atrial fibrillation), as digoxin can facilitate antegrade conduction along the accessory pathway and precipitate ventricular fibrillation 3, 5
• Suspected sick sinus syndrome without pacemaker protection 3
• Previous documented digoxin intolerance 3, 6

Common Pitfalls to Avoid

• Do not rely solely on digoxin levels—toxicity can occur even within the therapeutic range (0.5-1.2 ng/mL) when electrolyte disturbances or drug interactions are present 5, 1, 7
• Do not assume normal serum creatinine means normal renal function in elderly patients—calculate creatinine clearance, as advanced age indicates diminished renal function even with normal laboratory values 3, 4
• Do not ignore subtle symptoms—confusion, anorexia, and mild nausea in elderly patients may be early signs of digoxin toxicity rather than unrelated geriatric complaints 5, 7
• Do not add mirabegron without checking current digoxin dose—many elderly patients are already on inappropriately high doses (0.25 mg daily), which should be reduced before adding any P-glycoprotein inhibitor 2, 8

Clinical Bottom Line

The combination of mirabegron and digoxin is not contraindicated but requires the same level of vigilance as combining digoxin with amiodarone, macrolides, or other P-glycoprotein inhibitors 1. In elderly patients with heart conditions, proactive dose reduction of digoxin (to 0.125 mg daily or every other day) before initiating mirabegron, combined with close monitoring of levels and clinical status, can safely prevent toxicity while maintaining therapeutic benefit 3, 2.