Are there any contraindications to administering oral (po) metoprolol (Lopressor) and epoprostenol (Flolan) concurrently?

Contraindications to Concurrent Administration of Oral Metoprolol and Epoprostenol

Concurrent administration of oral metoprolol and epoprostenol is contraindicated in patients with systolic heart failure, as epoprostenol has been shown to increase mortality in this population when combined with standard heart failure therapy, which often includes beta-blockers like metoprolol. 1

Mechanism of Contraindication

The contraindication is based on several important clinical considerations:

1. Evidence from clinical trials:

   • The FIRST (Flolan International Randomized Survival Trial) study demonstrated that epoprostenol in patients with systolic heart failure resulted in a strong trend toward increased mortality despite hemodynamic improvements 1
   • The trial was terminated early due to safety concerns, leading to a formal contraindication for epoprostenol in systolic heart failure patients

2. Hemodynamic concerns:

   • Beta-blockers like metoprolol reduce heart rate and contractility
   • Epoprostenol causes systemic vasodilation
   • The combination may lead to excessive hypotension and decreased cardiac output in vulnerable patients

Specific Patient Populations at Risk

• Heart failure patients: Absolutely contraindicated based on the FIRST trial results 1
• Patients with severe hypotension: Combined vasodilatory effects may worsen hypotension
• Patients with bradycardia: Beta-blockade from metoprolol may worsen bradycardia that can occur with epoprostenol

Appropriate Use of Each Medication

Epoprostenol

• Indicated for: Pulmonary arterial hypertension (PAH), particularly in severe cases or WHO functional class III-IV 1
• Administration: Continuous intravenous infusion through a permanent indwelling central venous catheter
• Caution: Sudden disruption/withdrawal can lead to life-threatening PAH rebound 1

Metoprolol

• Indicated for: Hypertension, angina, post-MI, heart failure (when appropriately titrated)
• Contraindicated in: Cardiogenic shock, severe bradycardia, heart block
• Caution: Should be used cautiously in patients with bronchospastic disease due to its cardioselectivity 2

Alternative Approaches

If both medications are clinically necessary:

1. Consider alternative beta-blockers: Some clinicians may consider carvedilol as an alternative to metoprolol in certain situations 3

2. For PAH patients needing beta-blockade:

   • Consider inhaled prostanoids instead of IV epoprostenol
   • Use lowest effective doses of both medications with careful hemodynamic monitoring
   • Consider endothelin receptor antagonists or PDE-5 inhibitors as alternative PAH therapies 1

Monitoring Requirements

If these medications must be used together despite contraindications:

• Continuous hemodynamic monitoring initially
• Regular assessment of blood pressure, heart rate, and signs of heart failure
• Close monitoring for signs of hypotension, bradycardia, or worsening heart failure
• Regular ECG monitoring

Summary

The combination of oral metoprolol and epoprostenol should be avoided in patients with systolic heart failure due to increased mortality risk. In other patient populations, extreme caution should be exercised with close monitoring for hemodynamic compromise if both medications are deemed necessary.