What are the potential interactions between Paxlovid (nirmatrelvir/ritonavir) and metoprolol?

Potential Interactions Between Paxlovid and Metoprolol

Paxlovid (nirmatrelvir/ritonavir) can significantly increase metoprolol plasma concentrations by inhibiting CYP2D6, potentially causing bradycardia and hypotension, requiring dose reduction of metoprolol by 50% or temporary switch to a beta-blocker with less dependence on CYP metabolism during the 5-day Paxlovid treatment course.

Mechanism of Interaction

The interaction between Paxlovid and metoprolol occurs through multiple pathways:

1. CYP2D6 Inhibition: Ritonavir, a component of Paxlovid, inhibits CYP2D6 enzyme 1, which is the primary metabolic pathway for metoprolol.

2. Magnitude of Effect: Similar drug interactions with CYP2D6 inhibitors have shown significant increases in metoprolol exposure:

   • Imatinib increased metoprolol AUC by 23% 2
   • Gefitinib increased metoprolol AUC by 35% 2

3. Narrow Therapeutic Window Concern: Metoprolol has a relatively narrow therapeutic window, making this interaction clinically significant 1.

Clinical Consequences

The increased metoprolol concentration can lead to:

• Excessive beta-blockade
• Bradycardia (heart rate <60 bpm)
• Hypotension
• Fatigue
• Dizziness
• Heart block

Management Recommendations

Option 1: Dose Adjustment

• Reduce metoprolol dose by approximately 50% during the 5-day course of Paxlovid 1
• Monitor heart rate and blood pressure daily
• Return to original dose after completing Paxlovid treatment

Option 2: Temporary Medication Switch

• Switch to a beta-blocker with less dependence on CYP metabolism (e.g., atenolol, which is primarily renally eliminated)
• Resume metoprolol after completing the 5-day Paxlovid course

Option 3: Alternative COVID-19 Treatment

• If the patient is on a high dose of metoprolol that cannot be safely reduced, or has unstable cardiovascular disease, consider alternative COVID-19 treatments

Monitoring Parameters

1. Heart Rate: Monitor for bradycardia (HR <60 bpm)
2. Blood Pressure: Watch for hypotension
3. Symptoms: Assess for dizziness, fatigue, or syncope
4. ECG: Consider in patients with pre-existing conduction abnormalities

Special Considerations

• Elderly Patients: More susceptible to adverse effects due to reduced clearance of medications 1
• Renal Impairment: May further increase metoprolol concentrations 1
• Heart Failure: Patients may be more sensitive to hemodynamic changes
• Concomitant QT-prolonging Medications: Increased risk of cardiac arrhythmias 1

Practical Application

1. Before Starting Paxlovid:

   • Review current metoprolol dose and indication
   • Assess baseline heart rate and blood pressure
   • Consider temporary dose reduction or medication switch

2. During Paxlovid Treatment:

   • Monitor vital signs daily
   • Educate patient about symptoms requiring medical attention
   • Avoid adding other medications that could compound the interaction

3. After Completing Paxlovid:

   • Return to original metoprolol regimen
   • Reassess heart rate and blood pressure

This interaction requires careful management but should not necessarily preclude the use of Paxlovid in patients who would benefit from early COVID-19 treatment, as long as appropriate adjustments and monitoring are implemented.