Medical Editor: John P. Cunha, DO, FACOEP
What Is Entresto?
Entresto (sacubitril and valsartan) is a combination of a neprilysin inhibitor and an angiotensin II receptor blocker indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.
What Are Side Effects of Entresto?
Common side effects of Entresto include:
- low blood pressure (hypotension),
- high blood potassium (hyperkalemia),
- dizziness, and
- kidney (renal) failure
Dosage for Entresto
The recommended starting dose of Entresto is 49/51 mg twice-daily. Double the dose of Entresto after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice-daily, as tolerated by the patient.
What Drugs, Substances, or Supplements Interact with Entresto?
Entresto may interact with:
- angiotensin-converting-enzyme (ACE) inhibitors,
- other angiotensin receptor blockers (ARBs),
- potassium-sparing diuretics,
- nonsteroidal anti-inflammatory drugs (NSAIDs), or
Tell your doctor all medications and supplements you use.
Entresto During Pregnancy and Breastfeeding
Entresto is not recommended for use during pregnancy. It may harm a fetus. Entresto is not recommended for use while breastfeeding.
Our Entresto (sacubitril and valsartan) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Clinically significant adverse reactions that appear in other sections of the labeling include:
- Angioedema [see WARNINGS AND PRECAUTIONS]
- Hypotension [see WARNINGS AND PRECAUTIONS]
- Impaired Renal Function [see WARNINGS AND PRECAUTIONS]
- Hyperkalemia [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adult Heart Failure
In the PARADIGM-HF trial, subjects were required to complete sequential enalapril and ENTRESTO run-in periods of (median) 15 and 29 days, respectively, prior to entering the randomized double-blind period comparing ENTRESTO and enalapril. During the enalapril run-in period, 1,102 patients (10.5%) were permanently discontinued from the study, 5.6% because of an adverse event, most commonly renal dysfunction (1.7%), hyperkalemia (1.7%) and hypotension (1.4%). During the ENTRESTO run-in period, an additional 10.4% of patients permanently discontinued treatment, 5.9% because of an adverse event, most commonly renal dysfunction (1.8%), hypotension (1.7%) and hyperkalemia (1.3%). Because of this run-in design, the adverse reaction rates described below are lower than expected in practice.
In the double-blind period, safety was evaluated in 4,203 patients treated with ENTRESTO and 4,229 treated with enalapril. In PARADIGM-HF, patients randomized to ENTRESTO received treatment for up to 4.3 years, with a median duration of exposure of 24 months; 3,271 patients were treated for more than one year. Discontinuation of therapy because of an adverse event during the double-blind period occurred in 450 (10.7%) of ENTRESTO treated patients and 516 (12.2%) of patients receiving enalapril.
Adverse reactions occurring at an incidence of ≥ 5% in patients who were treated with ENTRESTO in the double-blind period are shown in Table 2.
Table 2: Adverse Reactions Reported in ≥ 5% of Patients Treated with ENTRESTO in the Double-Blind Period
(n = 4,203)
(n = 4,229)
|Renal failure/acute renal failure||5||5|
In the PARADIGM-HF trial, the incidence of angioedema was 0.1% in both the enalapril and ENTRESTO run-in periods. In the double-blind period, the incidence of angioedema was higher in patients treated with ENTRESTO than enalapril (0.5% and 0.2%, respectively). The incidence of angioedema in Black patients was 2.4% with ENTRESTO and 0.5% with enalapril [see WARNINGS AND PRECAUTIONS].
Orthostasis was reported in 2.1% of patients treated with ENTRESTO compared to 1.1% of patients treated with enalapril during the double-blind period of PARADIGM-HF. Falls were reported in 1.9% of patients treated with ENTRESTO compared to 1.3% of patients treated with enalapril.
Pediatric Heart Failure
The adverse reactions observed in pediatric patients 1 to <18 years old who received treatment with ENTRESTO were consistent with those observed in adult patients.
Hemoglobin and Hematocrit
Decreases in hemoglobin/hematocrit of > 20% were observed in approximately 5% of both ENTRESTO-and enalapriltreated patients in the double-blind period in PARADIGM-HF.
Increases in serum creatinine of > 50% were observed in 1.4% of patients in the enalapril run-in period and 2.2% of patients in the ENTRESTO run-in period. During the double-blind period, approximately 16% of both ENTRESTO-and enalapril-treated patients had increases in serum creatinine of > 50%.
Potassium concentrations > 5.5 mEq/L were observed in approximately 4% of patients in both the enalapril and ENTRESTO run-in periods. During the double-blind period, approximately 16% of both ENTRESTO-and enalapriltreated patients had potassium concentrations > 5.5 mEq/L.
The following additional adverse reactions have been reported in postmarketing experience. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypersensitivity including rash, pruritus, and anaphylactic reaction
Read the entire FDA prescribing information for Entresto (Sacubitril and Valsartan Film-coated Tablets for Oral Administration)