Sacubitril; Valsartan with Zofenopril Interaction Details
Brand Names Associated with Sacubitril; Valsartan
- Entresto®
- Valsartan and Sacubitril
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 09, 2023
Interaction Effect
Increased risk of adverse events (ie, hypotension, syncope, hyperkalemia, changes in renal function, acute renal failure)
Interaction Summary
Dual blockade of the renin-angiotensin-aldosterone system with concomitant use of an ACE inhibitor and an angiotensin receptor blocker (ARB) was associated with an increased incidence of side effects. In patients with established atherosclerotic disease, heart failure, or diabetes with end organ damage, coadministration of an ACE inhibitor and an ARB resulted in an increased incidence of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) as compared with either agent alone. Concomitant use should generally be avoided; however, should coadministration be necessary, closely monitor blood pressure, renal function, and electrolytes . In a meta-analysis in patients with left ventricular dysfunction, the addition of an ACE inhibitor to ARB therapy was associated with an increased overall risk of adverse events leading to discontinuation of therapy compared with ACE inhibitor therapy alone .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Dual blockade of the renin-angiotensin-aldosterone system by concomitant use of an ACE inhibitor and an angiotensin II receptor blocker (ARB) may increase the risk of adverse events, including hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure). Concomitant use should generally be avoided; however, should coadministration be necessary, closely monitor blood pressure, renal function, and electrolytes.
Mechanism Of Interaction
Dual blockade of the renin-angiotensin-aldosterone system
Literature Reports
A) A systematic review and meta-analysis of 18,160 patients with heart failure or left ventricular dysfunction from 9 randomized trials revealed the addition of angiotensin receptor blocker (ARB) to ACE inhibitor therapy was associated with an increased risk of adverse events leading to discontinuation of therapy compared with ACE inhibitor therapy alone. All patients had a NYHA functional class II to IV heart failure, an ejection fraction of 45% or below, or had left ventricular dysfunction acutely postmyocardial infarction. Losartan, candesartan, valsartan, irbesartan, and telmisartan were involved. The follow-up duration varied from 4 weeks to 41 months. Analysis revealed combination therapy increased the risk of developing any adverse effect by 2.3%. The risk of hypotension increased 1.1%, risk of worsening renal function increased 1%, and risk of hyperkalemia increased 0.6%. However, the risk of angioedema or cough did not significantly differ between treatment arms. If combination strategy is warranted, patients should be monitored closely for potential adverse effects
Sacubitril; Valsartan Overview
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The combination of valsartan and sacubitril is usually used in combination with other medications to lower the risk of death and hospitalization in adults with certain types of heart failure. The combination of valsartan and sacubitril is also used to treat certain types of heart failure in children 1 year of age and older. Valsartan is in a class of medications called angiotensin II receptor antagonists. It works by blocking the action of certain natural substances that tighten the blood vessels, allowing the blood to flow more smoothly and the heart to pump more efficiently. Sacubitril is in a class of medications called neprilysin inhibitors. It works to help control blood volume.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.