Some people with heart failure need to take multiple medicines each day in order to keep their symptoms under control. Heart failure not only leads to issues in the heart but other organs in the body as well. This can lead to many different symptoms developing, which may need multiple medicines to manage. The approval of combination medicines, that contain more than one medicine, is changing the way that heart failure is being treated.
Entresto (en-TRESS-toh) was approved in 2015 as the first medicine in its class. Entresto treats heart failure and reduces your chances of going to the hospital and of dying from heart failure.
How Does It Work for Heart Failure?
Heart failure is when the heart doesn't fill with as much blood as it should, which leads to the heart not properly pumping blood out to the rest of the body. The heart may not pump as well as it should if the muscles around the heart have become too weak, or if the muscles around the heart have become thick and stiff. Heart failure is a serious medical condition that can lead to hospitalizations and death if not treated properly.
Heart failure can cause many symptoms that can affect multiple parts of the body. These symptoms include shortness of breath, swelling, coughing, weight gain, tiredness, loss of appetite, fast heartbeat, and confusion.
Entresto is an angiotensin receptor-neprilysin inhibitor (ARNi). It contains two active ingredients: sacubitril (a neprilysin inhibitor), and valsartan (an angiotensin II receptor blocker). Entresto relaxes your blood vessels, lowers sodium levels, and lowers the amount of fluid in your body, which allows your heart to not work as hard to pump blood through your body.
It also works to increase ejection fraction (EF) and deliver more blood from your heart to the rest of your body. Ejection fraction is the percentage of blood that leaves your heart when the lower chambers of your heart contract. Entresto works best in people with left ventricular ejection fraction (LVEF). LVEF is a heart failure condition where the left side of the heart pumps out less blood than normal.
How Do I Take It?
Entresto is approved for use in children 1 year old or older and in adults. It comes as a tablet and as oral pellets in a capsule (oral sprinkle) and is taken twice daily. A liquid suspension can also be made by crushing the tablets. If your health care provider prescribes the liquid suspension, your pharmacist will prepare this. If you are giving your child Entresto, the dosing of the medicine will depend on your child’s weight. The target dose is 97 milligrams/103 milligrams twice daily in adults. In children, the target dose depends on the child’s weight.
Oral tablet/oral suspension. Entresto tablets come as a 24 milligram/26 milligram, 49 milligram/51 milligram, and 97 milligram/103 milligram tablet. For adults, the 49 milligram/51 milligram tablets will usually be prescribed to get your treatment started. After 2-4 weeks, your dose will usually be increased to 97 milligrams/103 milligrams if your health care provider thinks that you are tolerating the medicine without experiencing any major side effects. For children, either Entresto 24 milligrams/26 milligrams or 49 milligrams/51 milligrams may be prescribed to get your child started on the medicine, depending on your child’s weight.
If you or your child is prescribed the liquid suspension, shake the bottle before giving the medicine to your child. Use an accurate measuring device to measure the dose. A household spoon is not an accurate measuring device and may cause you to take or give the wrong dose to your child. Ask your pharmacist to recommend an appropriate measuring device.
Oral sprinkle. Entresto sprinkle comes as a 6 milligram/6 milligram pellet and a 15 milligram/16 milligram pellet. Your prescription should come with “Instructions for Use,” which can tell you how to take or give the medicine to your child. When you are preparing to take or give Entresto sprinkle to your child, empty the pellets from the capsules onto 1 to 2 teaspoons of soft food, such as applesauce. It is important to eat the soft food immediately. The pellets must be swallowed with the soft food and cannot be chewed.
How Was It Studied for Heart Failure?
Three clinical studies were done to look at the safety and efficacy of Entresto.
The first study compared the use of Entresto against enalapril, which is another medicine used in people with heart failure. This study looked to see if Entresto was better than enalapril in reducing the number of hospitalizations and death due to heart failure. In the study, people’s heart failure severity had to meet a certain criteria, including having an ejection fraction of 35% or less and meeting a certain level of b-type natriuretic peptide (BNP) in the blood. BNP is a protein found in the blood that is made by your heart when it is working too hard.
Entresto was given as 200 milligrams twice a day while enalapril was given as 10 milligrams twice a day for an average of 27 months. People in the study were 18 years of age or older and included people who were White Americans, African Americans, Asian Americans, Native Americans, or those classified as “Other,” where their race wasn’t specified. The average age was 64, and around 80% were male.
The second study compared the use of Entresto against valsartan, which is another medicine used in people with heart failure with preserved ejection fraction (HFpEF). HFpEF happens when your heart muscle is too stiff to fill with blood properly. The study looked to see if Entresto was better than valsartan in reducing the number of hospitalizations and death due to heart failure. In the study, people’s ejection fraction had to be 45% or higher and people had to meet a certain BNP level in their blood.
Entresto was given as 97 milligrams/103 milligrams and valsartan as 160 milligrams twice daily for an average of 35 months. People in the study were 50 years of age or older and included people who were White Americans, African Americans, Asian Americans, or “Other” where their race wasn’t specified. The average age was 73.
The third study was conducted to see the clinical benefits in children with left ventricular systolic dysfunction (LVSD) when using Entresto in children (more than 1 month of age and less than 18 years of age). LVSD is when the left ventricle (the left bottom chamber of the heart) cannot contract normally. The study looked at N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in people using Entresto compared to enalapril. NT-proBNP is another type of protein that can be found in the blood of people with heart failure, when your heart is experiencing increased stress.
What were the benefits?
For reducing the number of hospitalizations and death from heart failure:
- Compared to enalapril, Entresto reduced the risk of people going to the hospital or dying due to their heart failure. People taking Entresto had a lower percentage of heart failure events that lead to hospitalization or death at 21.8% compared to enalapril at 26.5%.
- Compared to valsartan, Entresto reduced the risk of people going to the hospital or dying from their heart failure. People taking Entresto had lower hospitalization/death rates (894 events) compared to valsartan (1,009 events).
For showing heart failure benefits in children:
- Entresto showed a lower NT-proBNP in the body compared to enalapril, which may lead to an improvement in heart failure in children.
How Can I Tell If It Is Working?
Entresto relaxes blood vessels and removes fluid from the body. You should start to see your body carrying less fluid, which may result in weight loss. Talk to your health care provider if you are still experiencing symptoms that are bothering you. Your health care provider may add other medicines or change your medicines to manage your heart failure symptoms. Entresto also lowers your chances of going to the hospital and of death from heart failure.
What Are the Side Effects, and How Can I Manage Them?
The most common side effects are low blood pressure, high potassium level, cough, dizziness, and kidney failure.
Low blood pressure can cause confusion, dizziness, fainting, headache, nausea, and heart palpitations. Drinking water and eating salty foods can help raise your blood pressure.
If you are experiencing dizziness, immediately sit down to prevent yourself from fainting.
If you are experiencing a cough that is bothering you or won’t go away, call your health care provider. They can offer advice on how to manage it.
Because Entresto can cause low blood pressure and dizziness, do not drive or do other activities that require alertness or coordination until you know how Entresto affects you.
Taking Entresto may increase your potassium levels (hyperkalemia). Generally, slightly higher potassium levels should not cause symptoms. On the other hand, very high levels of potassium can cause you to experience tiredness, muscle weakness, slow heartbeat or feeling of skipped heartbeats, nausea, vomiting, trouble breathing, or abnormal heart rhythm. Call your health care provider right away if you experience any of these symptoms.
Kidney failure may occur when taking Entresto. Talk to your health care provider if you already have kidney problems or have had kidney problems in the past. Call your health care provider right away if you have any of the following symptoms:
- Reduced need to pee
- Swelling in your feet, ankles, or legs
- Weakness or unusual tiredness
- Difficulty catching your breath
- Chest pain/pressure
- Confusion
- Nausea
- Seizures
What Types of Drug Interactions Can Happen?
You should not take Entresto with a medicine called an ACE inhibitor. Taking these two medicines together can increase your risk of developing swelling all around your body, also known as angioedema. Do not take Entresto within 36 hours of stopping an ACE inhibitor and vice versa.
Entresto contains two medicines, sacubitril and valsartan. Valsartan is classified as an angiotensin II receptor blocker (ARB). Entresto should not be taken with another ARB, as this can increase the risk of side effects. Tell your health care provider if you have ever had angioedema from taking an ACE inhibitor or an ARB. If you have, then you should not take Entresto.
You should not take Entresto with a medicine called aliskiren, which is a blood pressure medicine, if you have diabetes or kidney problems.
Taking certain medicines with Entresto can increase the potassium level in your blood. These medicines include amiloride, spironolactone, triamterene, potassium supplements, or salt substitutes. Having too much potassium in your blood can increase the risk of side effects.
People with kidney problems, especially older adults, may worsen their kidney problems when taking Entresto with NSAIDs.
Taking Entresto with lithium can increase the lithium levels in the blood. Too much lithium in your blood can increase your risk of side effects.
This is not a complete list of medicines that may interact with Entresto. Tell your pharmacist or health care provider about all the prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, or other supplements you take or have recently taken. This will help them determine if there are any interactions with Entresto or if you need a dosage adjustment. Talk to your health care provider about all your medical conditions.
Is There a Cost Savings Program?
There is a free trial offer from the manufacturer that may allow you to receive a onetime, 30-day supply of Entresto. Whether you are eligible depends on if you have a prescription for Entresto and if you have just recently started treatment. You can find out more at www.entresto.com/financial-support.
