Cholesterol Medications Safe to Take with Entresto (Sacubitril/Valsartan)
Rosuvastatin is the safest cholesterol medication to take with Entresto (sacubitril/valsartan) due to its lower risk of drug-drug interactions compared to other statins. 1
Drug Interaction Concerns with Entresto
- Sacubitril, a component of Entresto, can inhibit the excretion of certain statins, potentially increasing serum statin concentrations and the risk of muscle-related toxicity 1
- Life-threatening rhabdomyolysis has been reported with the co-administration of atorvastatin and sacubitril/valsartan, highlighting the importance of careful selection of cholesterol medications 1
- Entresto is primarily used in heart failure with reduced ejection fraction, where cholesterol management is often also needed 2, 3
Recommended Cholesterol Medications with Entresto
Preferred Options:
- Rosuvastatin: Has less drug-drug interaction with sacubitril, making it a safer choice when combined with Entresto 1
- Pravastatin: Less dependent on CYP3A4 metabolism, which reduces potential interactions with Entresto 3
- Fluvastatin: Has different metabolic pathways that make it less likely to interact significantly with Entresto 3
Use with Caution:
- Atorvastatin: If used with Entresto, should be started at a lower dose (20 mg daily) and titrated cautiously with regular monitoring of creatine kinase (CK), liver function, and renal function 1
- Ezetimibe: Can be considered as an add-on or alternative therapy, particularly in patients who cannot tolerate statins 3
Avoid:
- Simvastatin and Lovastatin: These are extensively metabolized by CYP3A4 and have higher risk of interactions with medications that affect this pathway 3
- Pitavastatin: Should be avoided due to potential interactions 3
Monitoring Recommendations
- Check baseline liver function tests and CK levels before initiating combination therapy 3
- Monitor for symptoms of muscle toxicity (myalgia, weakness, dark urine) 1
- Perform follow-up laboratory testing 4-12 weeks after initiation and periodically thereafter 3
- Assess renal function regularly, as both Entresto and certain statins can affect kidney function 4
Special Considerations
- For patients at very high cardiovascular risk who require intensive lipid lowering, consider PCSK9 inhibitors (evolocumab, alirocumab) which work through different mechanisms and may have fewer interactions with Entresto 3, 5
- Bile acid sequestrants (colesevelam, cholestyramine) could be alternative options for patients who cannot tolerate statins, but should be taken at least 2 hours before or 4 hours after Entresto to avoid interference with absorption 5
- In patients with diabetes and heart failure, careful selection of lipid-lowering therapy is particularly important 3
Clinical Pitfalls to Avoid
- Never start high-dose statin therapy immediately when combining with Entresto; always begin with lower doses and titrate gradually 1
- Do not ignore symptoms of muscle pain in patients on combination therapy, as this could be an early sign of rhabdomyolysis 1
- Avoid assuming that all statins carry the same risk when combined with Entresto; their interaction potential varies significantly 3
- Regular monitoring is essential, as adverse effects may develop even after months of stable combination therapy 3