What are the considerations for using Entresto (sacubitril and valsartan) in patients at risk of hypermagnesemia?

Entresto (Sacubitril/Valsartan) and Hypermagnesemia: Clinical Considerations

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

Risk Factors for Hypermagnesemia with Entresto

• Renal insufficiency: Patients with eGFR <30 mL/min/1.73m² are at highest risk for developing hypermagnesemia when taking Entresto due to reduced renal clearance of magnesium 1, 2
• Concomitant medications: Particular caution is needed when combining Entresto with:
  • Magnesium-containing medications or supplements 1
  • Mineralocorticoid receptor antagonists (spironolactone, eplerenone) which can independently cause hyperkalemia and may worsen electrolyte imbalances 1

Monitoring Recommendations

• Baseline assessment: Check serum magnesium, potassium, and renal function before initiating Entresto 1
• Follow-up monitoring: Regular monitoring of electrolytes and renal function is essential, especially in:
  • Patients with CKD stages 3B-5 1
  • Elderly patients 1
  • Those on concomitant medications affecting electrolyte balance 1

Clinical Decision Algorithm

1. For patients with normal renal function (eGFR >60 mL/min/1.73m²):

   • Entresto can be initiated at standard doses with routine electrolyte monitoring 1, 2

2. For patients with moderate renal impairment (eGFR 30-60 mL/min/1.73m²):

   • Start Entresto at lower doses and titrate gradually 1
   • Monitor electrolytes (including magnesium) more frequently 1, 2

3. For patients with severe renal impairment (eGFR <30 mL/min/1.73m²):

   • Use Entresto with extreme caution or consider alternative therapies 1
   • More frequent monitoring of electrolytes is mandatory 1, 2
   • Recent evidence suggests potential benefits in end-stage kidney disease patients, but requires close monitoring 3, 4

4. For patients on dialysis:

   • Limited data exists, but small studies suggest potential benefits with careful monitoring 3
   • Consult with nephrology before initiating therapy 1, 3

Special Considerations

• Heart failure with reduced ejection fraction (HFrEF): Entresto is indicated as a replacement for ACE inhibitors or ARBs in HFrEF patients to reduce cardiovascular mortality and hospitalization 1, 5

• Chronic kidney disease: While Entresto may provide cardiovascular and renal benefits in CKD patients, the risk of electrolyte abnormalities increases with declining renal function 2, 4

• Concomitant medications: Avoid triple combination of Entresto with ACE inhibitors and MRAs due to significantly increased risk of hyperkalemia and other electrolyte disturbances 1

Clinical Pearls and Pitfalls

• Wait period: Allow a 36-hour washout period when switching from an ACE inhibitor to Entresto to minimize risk of angioedema 5

• Hypotension risk: Entresto causes more symptomatic hypotension than ACE inhibitors, which may require dose adjustment 5, 1

• Patient education: Advise patients to avoid over-the-counter potassium supplements, potassium-based salt substitutes, and high-magnesium foods/supplements 1

• Electrolyte monitoring: Regular monitoring of not just potassium but also magnesium levels is essential, particularly in patients with risk factors for hypermagnesemia 1, 2