Can macitentan (Endothelin receptor antagonist) cause hyperkalemia (elevated potassium levels)?

Macitentan and Hyperkalemia: Clinical Implications

Macitentan does not cause hyperkalemia and is not listed among medications known to increase potassium levels in clinical guidelines. Unlike many other cardiovascular medications, macitentan (an endothelin receptor antagonist) is not associated with potassium retention or hyperkalemia risk.

Medications That DO Cause Hyperkalemia

According to the European Society of Cardiology expert consensus document on hyperkalemia management 1, medications that commonly cause hyperkalemia include:

1. Renin-angiotensin-aldosterone system inhibitors (RAASi):

   • ACE inhibitors
   • Angiotensin receptor blockers (ARBs)
   • Direct renin inhibitors (aliskiren)

2. Potassium-sparing agents:

   • Mineralocorticoid receptor antagonists (spironolactone, eplerenone)
   • Other potassium-sparing diuretics (triamterene, amiloride)

3. Other medications:

   • NSAIDs
   • Beta-blockers
   • Calcineurin inhibitors (cyclosporine, tacrolimus)
   • Trimethoprim-sulfamethoxazole
   • Heparin
   • Digitalis

Notably, macitentan is not included in this comprehensive list of medications associated with hyperkalemia 1.

Endothelin Receptor Antagonists and Electrolyte Balance

Macitentan is an endothelin receptor antagonist (ERA) used primarily in pulmonary arterial hypertension. Unlike medications that affect the renin-angiotensin-aldosterone system, ERAs like macitentan work through different mechanisms:

• They block endothelin receptors, primarily affecting vascular tone
• They do not directly impact renal potassium handling 2
• Their safety profile differs from medications known to cause hyperkalemia

Clinical Implications

When prescribing cardiovascular medications, it's important to recognize which ones carry hyperkalemia risk:

• High risk: ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists are explicitly identified as causing hyperkalemia in multiple guidelines 1

• No established risk: Macitentan is not mentioned as causing hyperkalemia in any of the comprehensive guidelines on medication-induced hyperkalemia 1, 3, 4

Monitoring Recommendations

While macitentan itself doesn't require potassium monitoring for hyperkalemia risk, patients on multiple cardiovascular medications should have regular electrolyte monitoring, especially if they have:

• Chronic kidney disease
• Heart failure
• Diabetes mellitus
• Advanced age
• Concomitant use of medications known to cause hyperkalemia

Prevention of Medication-Induced Hyperkalemia

For medications that DO cause hyperkalemia (unlike macitentan):

• Monitor serum potassium regularly
• Avoid combinations of multiple potassium-retaining drugs when possible
• Consider potassium binders for chronic management in high-risk patients
• Adjust medication doses based on renal function

Conclusion

Based on current clinical guidelines and pharmacological evidence, macitentan does not cause hyperkalemia. When managing patients with cardiovascular conditions requiring multiple medications, it's important to recognize which agents carry hyperkalemia risk and monitor accordingly.