What is Entresto - Sacubitril and Valsartan used for?
Entresto is a heart medicine that contains the active ingredients sacubitril and valsartan. It is used in adults with chronic heart failure who experience symptoms of the disease. Heart failure is characterized by the inability of the heart to pump the required amount of blood into the bloodstream.
How is Entresto - Sacubitril and Valsartan used?
Entresto is available as tablets (24 mg sacubitril / 26 mg valsartan, 49 mg sacubitril / 51 mg valsartan, and 97 mg sacubitril / 103 mg valsartan). Entresto can only be obtained with a prescription.
Entresto tablets should be taken twice a day. The recommended starting dose is one Entresto 49 mg / 51 mg tablet twice a day. The dose is then doubled after 2-4 weeks at 97 mg / 103 mg twice a day. For some patients the doctor may decide lower doses. For more information, see the summary of product characteristics (also part of the EPAR).
How does Entresto - Sacubitril and Valsartan work?
The two active ingredients of Entresto, sacubitril and valsartan, act in different ways. Sacubitril blocks the breakdown of natriuretic peptides produced in the body. Natriuretic peptides determine the passage of sodium and water into the urine, thus reducing the strain on the heart. Natriuretic peptides also reduce blood pressure and protect the heart from the development of fibrosis (scar tissue) secondary to heart failure.
Valsartan is an "angiotensin II receptor antagonist"; this means that it inhibits the action of a hormone known as angiotensin II. The effects of angiotensin II can be harmful in patients with heart failure. By blocking the receptors normally associated with angiotensin II, valsartan blocks the harmful effects of the hormone on the heart, as well as reducing blood pressure, allowing the blood vessels to dilate.
What benefit has Entresto - Sacubitril and Valsartan shown during the studies?
In the main study, Entresto was compared to enalapril, another drug used for heart failure. The patients who participated in the study had chronic heart failure with manifest symptoms of the disease and reduced ejection fraction (the portion of blood expelled from the heart). In the group treated with Entresto, 21.8% (914 out of 4 187) of patients died of cardiac and circulatory problems or were hospitalized for heart failure compared to 26.5% (1 117 of 4 212) of patients treated with enalapril. In general, patients were monitored for approximately 27 months. During this period they took the medicine on average for about 24 months. The study was stopped early because convincing evidence emerged regarding the greater efficacy of Entresto compared to enalapril.
What is the risk associated with Entresto - Sacubitril and Valsartan?
The most common side effects with Entresto (which may affect more than 1 in 10 people) are high blood levels of potassium, low blood pressure and reduced kidney function. A potentially serious but uncommon side effect (affects less than 1 in 100 people) is angioedema (rapid swelling of deeper skin tissues and those around the throat resulting in difficulty breathing). For the full list of all side effects reported with Entresto, see the package leaflet.
Entresto should not be taken with drugs known as ACE inhibitors (used to treat heart failure and high blood pressure). It must not be taken by patients who have suffered from angioedema, by patients with severe liver disease or by pregnant women. For the full list of usage restrictions, refer to the package insert.
Why has Entresto - Sacubitril and Valsartan been approved?
The Agency's Committee for Medicinal Products for Human Use (CHMP), after reviewing the studies conducted on the drug, decided that Entresto's benefits are greater than its risks and recommended that it be approved for use in the EU. The main study revealed that Entresto reduced the number of deaths resulting from heart and circulatory problems, as well as hospitalization due to heart failure.
The serious side effects attributed to Entresto in the main study were similar to those reported for enalapril, a substance already authorized for use in cases of heart failure. The use of valsartan, one of the active ingredients of the medicine, is well established for the treatment of hypertension and heart failure; its side effects are well known.
What measures are being taken to ensure the safe and effective use of Entresto - Sacubitril and Valsartan?
A risk management plan has been developed to ensure that Entresto is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Entresto, including the appropriate precautions to be followed by healthcare professionals and patients.
Further information is available in the summary of the risk management plan.
Other information on Entresto - Sacubitril and Valsartan
For the full version of the EPAR and the summary of the Entresto risk management plans, consult the Agency's website: ema.europa.eu/Find medicine / Human medicines / European public assessment reports. For more information on therapy with Entresto, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.
