What are the potential interactions between Myrbetriq (mirabegron) and Zoloft (sertraline), Namenda (memantine), Clonazepam, and Toprol (metoprolol)?

Drug Interactions Between Myrbetriq and Concurrent Medications

Myrbetriq (mirabegron) can be safely used with Namenda (memantine) and clonazepam, but requires careful monitoring when combined with Zoloft (sertraline) and Toprol (metoprolol) due to clinically significant pharmacokinetic interactions.

Key Interaction: Metoprolol (Toprol)

Mirabegron significantly increases metoprolol exposure and requires dose adjustment or enhanced monitoring. 1, 2

• Mirabegron acts as a moderate CYP2D6 inhibitor, increasing metoprolol maximum concentration (Cmax) by 1.90-fold and total exposure (AUC) by 3.29-fold 2
• Mean metoprolol half-life increases from 2.96 to 4.11 hours when combined with mirabegron 2
• Monitor for excessive beta-blockade effects including bradycardia, hypotension, and dizziness 1, 2
• Consider reducing metoprolol dose by approximately 50-70% when initiating mirabegron, or increase monitoring frequency for heart rate and blood pressure 2

Moderate Interaction: Sertraline (Zoloft)

Sertraline is metabolized by CYP2D6, and mirabegron may increase sertraline levels, though this combination is not contraindicated. 1

• Mirabegron inhibits CYP2D6 metabolism, which could increase systemic exposure to sertraline 1, 2
• Monitor for serotonergic side effects including nausea, drowsiness, tremor, and sexual dysfunction 3
• The FDA label specifically recommends "appropriate monitoring and dose adjustment may be necessary when mirabegron is coadministered with drugs metabolized by CYP2D6 enzyme" 1
• Sertraline is generally well-tolerated and has less effect on metabolism of other medications compared to other SSRIs 3

No Significant Interactions

Memantine (Namenda) and clonazepam have no known clinically significant interactions with mirabegron. 1

• Memantine is primarily renally eliminated and does not undergo significant CYP450 metabolism 3
• Clonazepam is metabolized by CYP3A4, not CYP2D6, avoiding the primary interaction pathway with mirabegron 3
• No dose adjustments are required for these medications when combined with mirabegron 1

Additional Monitoring Considerations

Blood pressure monitoring is essential when using mirabegron, particularly in combination with cardiovascular medications. 1, 4

• Mirabegron can cause dose-dependent increases in blood pressure (mean increases of 4.3 mmHg systolic and 1.7 mmHg diastolic in some populations) 1
• The combination of mirabegron with beta-blockers like metoprolol may have additive effects on heart rate 3
• Hypertension was among the most common adverse events in clinical trials lasting up to 12 months 5

Clinical Management Algorithm

Follow this stepwise approach when prescribing mirabegron with these medications: 1, 2

1. For metoprolol: Reduce metoprolol dose by 50% when initiating mirabegron 50 mg daily, monitor heart rate and blood pressure weekly for 4 weeks, then monthly 2

2. For sertraline: Continue current sertraline dose initially, monitor for increased serotonergic effects at weeks 2,4, and 8, reduce sertraline dose by 25% if adverse effects emerge 1

3. For memantine and clonazepam: No dose adjustment required, continue standard monitoring 1

4. Monitor renal function: Mirabegron is partially renally eliminated (approximately 20% of absorbed dose excreted unchanged in urine), which may be relevant in patients on multiple medications 6

Common Pitfalls to Avoid

• Do not assume all beta-blockers interact equally: The interaction is specific to CYP2D6-metabolized beta-blockers like metoprolol; atenolol (renally eliminated) has minimal interaction 3, 2
• The CYP2D6 inhibition by mirabegron is partially irreversible: Effects persist for approximately 2 weeks after discontinuation, requiring continued monitoring during this washout period 2
• Avoid abrupt discontinuation of metoprolol: If dose reduction is needed due to excessive beta-blockade, taper gradually to prevent rebound tachycardia 2