Entresto contains two active drugs combined into a single tablet: sacubitril and valsartan. These two ingredients work through different mechanisms but together help the heart pump more effectively and reduce strain on the cardiovascular system. Entresto comes in three tablet strengths, each with a roughly 1:1 ratio of the two drugs, plus a set of inactive ingredients that hold the tablet together and form its colored coating.
The Two Active Ingredients
Sacubitril and valsartan each target a different system in the body, and combining them is what makes Entresto distinct from older heart failure medications.
Sacubitril belongs to a class called neprilysin inhibitors. After you swallow the tablet, your body converts sacubitril into its active form, which blocks an enzyme called neprilysin. That enzyme normally breaks down natriuretic peptides, which are natural hormones that relax blood vessels, lower blood pressure, and help the kidneys remove excess sodium and fluid. By slowing the breakdown of these peptides, sacubitril lets them stay active longer, easing the workload on the heart.
Valsartan is an angiotensin II receptor blocker (ARB). Angiotensin II is a hormone that tightens blood vessels and raises blood pressure. Valsartan blocks the receptor that angiotensin II binds to, preventing that tightening effect. This lowers blood pressure and reduces the amount of effort the heart needs to push blood through the body.
The two drugs exist in the tablet as a single salt complex (sacubitril valsartan sodium), not as two separate granules mixed together.
Available Tablet Strengths
Entresto is sold in three strengths, labeled by the amount of each ingredient:
- 24/26 mg: 24.3 mg sacubitril and 25.7 mg valsartan
- 49/51 mg: 48.6 mg sacubitril and 51.4 mg valsartan
- 97/103 mg: 97.2 mg sacubitril and 102.8 mg valsartan
There is also a sprinkle formulation (oral pellets in a capsule) for patients who have difficulty swallowing tablets. The pellets contain the same active drug complex in different packaging.
Inactive Ingredients
Beyond the two active drugs, each Entresto tablet contains several inactive ingredients that serve as fillers, binders, and coatings. The tablet core includes colloidal silicon dioxide, crospovidone, low-substituted hydroxypropylcellulose, magnesium stearate (from a vegetable source), microcrystalline cellulose, and talc. These are standard pharmaceutical excipients that help the tablet hold its shape, dissolve properly, and stay stable on the shelf.
The film coating on the outside of each tablet contains hypromellose, iron oxide red, polyethylene glycol 4000, talc, and titanium dioxide. The different tablet strengths get their distinct colors from additional iron oxide pigments: the 24/26 mg and 97/103 mg tablets include iron oxide black, while the 49/51 mg tablets use iron oxide yellow instead.
The sprinkle formulation uses a slightly different set of coating and capsule shell materials, including a methacrylate copolymer, sodium lauryl sulfate, and shellac-based printing ink.
What Entresto Is Prescribed For
Entresto is FDA-approved for heart failure. In the landmark PARADIGM-HF trial, patients taking Entresto had a 21.8% rate of cardiovascular death or heart failure hospitalization over about 27 months, compared to 26.5% for patients on an older standard treatment. Cardiovascular death specifically occurred in 13.3% of the Entresto group versus 16.5% in the comparison group, and heart failure hospitalizations dropped from 15.6% to 12.8%.
Common Side Effects
Because both ingredients lower blood pressure, the most notable side effect is hypotension. About 18% of patients in clinical trials experienced clinically meaningful low blood pressure. Symptoms can include dizziness, lightheadedness, or feeling faint, particularly when standing up quickly.
High potassium levels (hyperkalemia) occur in roughly 16% of patients, which is worth knowing if you’re already taking potassium-sparing medications or eating a high-potassium diet. Angioedema, a type of rapid swelling under the skin, can occur but is uncommon. About 11% of patients in trials stopped taking Entresto due to side effects.
Why It Can’t Be Taken With ACE Inhibitors
One critical detail about Entresto’s composition: because sacubitril blocks neprilysin, combining it with an ACE inhibitor dramatically raises the risk of angioedema. Neprilysin and ACE both break down a substance called bradykinin, and blocking both pathways at once allows bradykinin to build up to dangerous levels. If you’re switching from an ACE inhibitor to Entresto, a mandatory 36-hour washout period is required between your last ACE inhibitor dose and your first Entresto dose. Valsartan (an ARB) does not carry this same risk, which is why it was chosen as the partner drug in this combination.