Entresto and Hypermagnesemia: Clinical Considerations

Risk Factors and Monitoring

The American Heart Association recommends that Entresto should be used with caution in patients at risk of hypermagnesemia, particularly those with moderate to severe renal dysfunction, as the valsartan component can potentially worsen electrolyte abnormalities 1, 2
Patients with renal insufficiency, specifically those with eGFR <30 mL/min/1.73m², are at highest risk for developing hypermagnesemia when taking Entresto due to reduced renal clearance of magnesium 2
Concomitant medications, such as magnesium-containing medications or supplements, and mineralocorticoid receptor antagonists, can increase the risk of hypermagnesemia and electrolyte imbalances 1, 2, 3, 4

The American College of Cardiology recommends baseline assessment of serum magnesium, potassium, and renal function before initiating Entresto, and regular monitoring of electrolytes and renal function, especially in patients with CKD stages 3B-5, elderly patients, and those on concomitant medications affecting electrolyte balance 1, 2, 5
For patients with normal renal function, Entresto can be initiated at standard doses with routine electrolyte monitoring, while patients with moderate renal impairment should start at lower doses and titrate gradually with more frequent monitoring of electrolytes 2
The American Heart Association suggests that patients on dialysis should be treated with caution, and consultation with nephrology is recommended before initiating Entresto therapy 2

The American College of Cardiology indicates that Entresto is indicated as a replacement for ACE inhibitors or ARBs in heart failure with reduced ejection fraction patients to reduce cardiovascular mortality and hospitalization 5
Avoiding triple combination of Entresto with ACE inhibitors and MRAs is recommended due to significantly increased risk of hyperkalemia and other electrolyte disturbances 1, 2
Patient education on avoiding over-the-counter potassium supplements, potassium-based salt substitutes, and high-magnesium foods/supplements is essential 2