Is it safe to use Keytruda (pembrolizumab) with spironolactone?

Safety of Pembrolizumab (Keytruda) with Spironolactone

Pembrolizumab (Keytruda) can be safely used concurrently with spironolactone as there are no known drug interactions between these medications.

Mechanism and Safety Considerations

• Pembrolizumab is an immune checkpoint inhibitor that works by blocking PD-1 receptors, enhancing T-cell immune responses against tumor cells 1
• Spironolactone is a potassium-sparing diuretic and aldosterone receptor antagonist with anti-androgenic properties 2
• These medications have different mechanisms of action and metabolic pathways, with no documented direct interactions 1

Monitoring Recommendations

For Spironolactone:

• Monitor serum potassium levels in patients with:
  • Renal insufficiency
  • Diabetes
  • Advanced age
  • Worsening heart failure
  • Risk for dehydration
  • Concomitant use of ACE inhibitors, ARBs, or NSAIDs 2, 3
• Routine potassium monitoring is not required in young, healthy women without risk factors for hyperkalemia 2, 4
• Most common side effects include diuresis (29%), menstrual irregularities (22%), and breast tenderness (17%) 2

For Pembrolizumab:

• Typical dosing is 200 mg every 3 weeks or 400 mg every 6 weeks 5, 6
• Monitor for immune-mediated adverse events, which occur in approximately 23.7% of patients 1
• Grade 3-5 adverse events occur in about 50.6% of patients on pembrolizumab 1

Special Considerations

• If the patient is using spironolactone for resistant hypertension:

  • Ensure proper blood pressure monitoring as pembrolizumab therapy continues 2
  • Consider that spironolactone is recommended as a fourth-line agent for resistant hypertension 2

• If the patient is using spironolactone for acne or hormonal issues:

  • Be aware that spironolactone is often used with combined oral contraceptives (COCs) 2, 4
  • The combination of spironolactone with drospirenone-containing COCs has been shown to be safe without increased risk of hyperkalemia 2, 4

Risk Mitigation

• Avoid the combination in patients with:

  • Severe renal impairment
  • History of hyperkalemia
  • Concomitant use of other potassium-sparing medications 2, 3

• For patients on both medications who develop dehydration (a potential side effect of pembrolizumab):

  • Monitor more closely for electrolyte abnormalities
  • Consider temporary dose adjustment of spironolactone if necessary 3

Conclusion

While there are no specific contraindications to using pembrolizumab with spironolactone, appropriate monitoring based on the patient's underlying conditions and other medications is prudent, with particular attention to potassium levels in high-risk patients.