Contraindicated Medications: Never Combine with Entresto
Some drug interactions with Entresto are so dangerous that the medications should never be used together. These are referred to as contraindications, meaning the risks far outweigh any potential benefits.
Angiotensin-Converting Enzyme (ACE) Inhibitors
One of the most critical warnings for Entresto is its interaction with ACE inhibitors. Entresto contains sacubitril, which blocks an enzyme that breaks down certain peptides, including bradykinin. ACE inhibitors, such as lisinopril (Zestril), enalapril (Vasotec), and ramipril (Altace), also increase bradykinin levels. Taking both medications together causes an excessive buildup of bradykinin, which dramatically increases the risk of angioedema—a rapid and potentially life-threatening swelling of the face, tongue, and throat.
To prevent this severe reaction, there must be a mandatory 36-hour "washout period" when switching from an ACE inhibitor to Entresto. Your doctor will provide specific instructions for stopping the ACE inhibitor and when to start Entresto safely.
Angiotensin II Receptor Blockers (ARBs)
The valsartan component of Entresto is an angiotensin II receptor blocker (ARB). Taking Entresto with another ARB, like losartan (Cozaar) or irbesartan (Avapro), effectively results in taking a double dose of the same type of medication. This can increase the risk of side effects, including low blood pressure (hypotension), kidney problems, and high potassium levels (hyperkalemia). For this reason, doctors will not prescribe Entresto alongside other ARBs.
Aliskiren
Aliskiren (Tekturna) is a direct renin inhibitor used to treat high blood pressure. Its interaction with Entresto is particularly dangerous for patients with diabetes or moderate-to-severe kidney impairment. The combination can significantly raise the risk of kidney problems, severe hypotension, and hyperkalemia. The concurrent use of Entresto with aliskiren is contraindicated in these high-risk patients.
Medications Requiring Extreme Caution and Monitoring
While not strictly forbidden for all patients, these medications require careful consideration, dose adjustment, and close medical supervision when used with Entresto.
Potassium-Sparing Diuretics and Potassium Supplements
Both Entresto and potassium-sparing diuretics, such as spironolactone (Aldactone) and triamterene (Dyrenium), can increase potassium levels in the blood. Taking them together, along with potassium supplements or potassium-containing salt substitutes, can lead to hyperkalemia. Hyperkalemia can cause serious heart rhythm problems and requires close monitoring through regular blood tests. Your doctor will manage this combination carefully, especially if you have pre-existing kidney problems or diabetes.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
NSAIDs like ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex) can increase the risk of kidney problems, including acute kidney failure, when combined with Entresto. This risk is heightened in older patients, those who are dehydrated, or individuals with pre-existing kidney issues. Short-term use of low-dose NSAIDs may be acceptable under a doctor's supervision, but regular or high-dose use is strongly discouraged. Acetaminophen (Tylenol) is generally considered a safer alternative for pain relief.
Lithium
Entresto can cause an increase in the concentration of lithium in the blood, leading to an increased risk of lithium toxicity. Symptoms of lithium toxicity can range from nausea, vomiting, and diarrhea to more severe neurological effects like confusion and seizures. If a patient must take both medications, a doctor will closely monitor their blood lithium levels and may need to lower the lithium dosage.
Comparison Table of Entresto Interactions
| Drug Class/Name | Examples | Interaction with Entresto | Clinical Impact | Management |
|---|---|---|---|---|
| ACE Inhibitors | lisinopril, ramipril, enalapril | Increased bradykinin levels | High risk of severe, life-threatening angioedema | 36-hour washout period before starting Entresto |
| Other ARBs | losartan, valsartan (Diovan) | Valsartan component overlaps | Increased risk of low blood pressure, high potassium, kidney problems | Do not combine; discontinue other ARB before starting Entresto |
| Aliskiren | Tekturna | Dual RAAS blockade | Increased risk of kidney failure, hypotension, hyperkalemia in patients with diabetes or kidney impairment | Contraindicated in diabetic patients; avoid in patients with renal impairment |
| Potassium-Sparing Diuretics/Supplements | spironolactone, triamterene | Additive potassium-increasing effect | High risk of hyperkalemia (dangerously high potassium levels) | Close monitoring of potassium levels; may require dose reduction |
| NSAIDs | ibuprofen, naproxen, celecoxib | Increased risk of kidney injury | Potential for worsening kidney function and acute kidney failure | Monitor kidney function; consider acetaminophen for pain |
| Lithium | Lithium (Lithobid) | Increased lithium blood levels | Risk of lithium toxicity, which can be severe or fatal | Close monitoring of lithium levels; potential dose reduction of lithium |
The Role of Patient Communication and Monitoring
Given the complexity of these interactions, open and honest communication with your healthcare provider is essential. Always provide a complete and current list of all medications, supplements, and over-the-counter products you are taking. Before starting Entresto, your doctor will perform blood tests to check your potassium and kidney function and will continue to monitor these throughout your treatment. This proactive approach helps ensure the medication is both safe and effective for your specific health needs.
Conclusion
Entresto is a powerful and effective medication for heart failure, but it is not compatible with all other drugs. Combining Entresto with ACE inhibitors, other ARBs, or aliskiren in diabetic patients can lead to severe, life-threatening outcomes. Other common drugs like NSAIDs, potassium supplements, and lithium also pose significant risks and require diligent medical oversight. A thorough review of your medication list with your doctor and pharmacist is the most crucial step in preventing dangerous drug interactions and ensuring your safety while on Entresto. Always follow their specific instructions and report any new or unusual symptoms immediately.
