From the Guidelines
Entresto (sacubitril/valsartan) can increase the risk of hyperkalemia, and patients should be closely monitored for potassium level elevations, especially in the first 1-2 weeks of therapy and after dose increases, as stated in the expert consensus document on the management of hyperkalaemia in patients with cardiovascular disease treated with renin angiotensin aldosterone system inhibitors 1. When initiating Entresto, baseline potassium levels should be less than 5.2 mEq/L. Key factors that increase the risk of hyperkalemia with Entresto include:
- Kidney dysfunction
- Concurrent use of other medications that raise potassium levels, such as ACE inhibitors, ARBs, potassium-sparing diuretics, and NSAIDs
- High-potassium foods and supplements It is crucial to avoid concurrent use of medications that can worsen hyperkalemia with Entresto when possible. If hyperkalemia develops, consider reducing the dose of Entresto or temporarily discontinuing it in severe cases (potassium >5.5 mEq/L). According to the European Heart Journal study 1, life-threatening hyperkalemia requires immediate treatment with a combination of calcium carbonate and hyperosmolar sodium, and potassium-lowering agents such as loop diuretics and potassium binders can be used to manage hyperkalemia. Patients with diabetes or chronic kidney disease require especially careful monitoring as they have higher baseline risk for potassium abnormalities, and the use of Entresto should be carefully weighed against the potential benefits and risks in these populations, as renin angiotensin aldosterone system inhibitors have a proven reduction of mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) 1.
From the FDA Drug Label
Through its actions on the RAAS, hyperkalemia may occur with sacubitril and valsartan [see Adverse Reactions (6. 1)]. Monitor serum potassium periodically and treat appropriately, especially in patients with risk factors for hyperkalemia such as severe renal impairment, diabetes, hypoaldosteronism, or a high potassium diet. Dosage reduction or interruption of sacubitril and valsartan may be required [see Dosage and Administration (2. 7)].
Hyperkalemia is a potential risk associated with Entresto (sacubitril and valsartan) due to its effects on the renin-angiotensin-aldosterone system (RAAS). To mitigate this risk, it is recommended to:
- Monitor serum potassium levels periodically
- Treat hyperkalemia appropriately
- Consider dosage reduction or interruption of sacubitril and valsartan if hyperkalemia occurs, especially in patients with risk factors such as:
From the Research
Hyperkalemia and Entresto
- Entresto, a combination of sacubitril and valsartan, is used to treat heart failure and has been shown to increase potassium levels in some patients 3.
- The use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), which are similar to valsartan, can be associated with hyperkalemia, particularly in patients with chronic renal insufficiency 4.
- Hyperkalemia can occur due to a combination of factors, including treatment with ACEi, potassium-sparing diuretics, and high dietary intake of potassium 5.
- Monitoring serum potassium levels is crucial in patients taking Entresto, especially those with risk factors for hyperkalemia, such as chronic kidney disease or excessive potassium intake 4, 6.
Risk Factors for Hyperkalemia
- Chronic renal insufficiency 4
- Excessive potassium intake from diet, supplements, or drugs 4, 5
- Use of potassium-sparing diuretics 5
- Comorbidities that reduce renal function 3