Endari is a brand-name prescription medication. It’s FDA-approved to reduce the number of sudden complications of sickle cell disease (SCD) and how severe they are. One of the main complications is pain crisis, which is severe pain across the body.

Endari is approved for use in adults as well as children ages 5 years and older.

SCD is an inherited disease that causes red blood cells to change shape. This can block blood flow, leading to a pain crisis.

Drug details

The active ingredient in Endari is an amino acid called L-glutamine. Amino acids make up proteins and are considered the “building blocks” of cells.

Endari comes as a powder that you can mix with certain foods or drinks and take by mouth. The drug is typically taken twice daily. Endari is available in one strength: 5 grams.

For more information on how to take Endari, see the “How to take Endari” section below.

FDA approval

Endari was approved by the Food and Drug Administration (FDA) in 2017. It is one of only three medications the FDA has approved for SCD in almost 20 years.

Effectiveness

For information about the effectiveness of Endari, see the “Endari for sickle cell disease” section below.

Endari is available only as a brand-name medication. It’s not currently available in generic form.

A generic drug is an exact copy of the active drug in a brand-name medication. Generics usually cost less than brand-name drugs.

The active ingredient in Endari is L-glutamine.

The Food and Drug Administration (FDA) approves prescription drugs such as Endari to treat certain conditions.

Endari for sickle cell disease

Endari is FDA-approved to reduce the number of sudden complications in people who have sickle cell disease (SCD) and how severe they are. For a list of complications, see “Sickle cell disease explained” below.

Endari is approved for use in adults as well as children ages 5 years and older.

Sickle cell disease explained

SCD is an inherited disease that causes red blood cells (RBCs) to change shape. Typically, RBCs are shaped like a disc. But with SCD, the cells become curved like a C (similar to a sickle). This can cause the RBCs to block normal blood flow.

RBCs carry oxygen throughout the body. But when they are sickle shaped, they can become stuck in blood vessels and block the normal flow of blood. When blood and oxygen can’t get to parts of the body easily, it can cause tissue damage. As a result, there can be complications such as:

  • pain crises* (episodes of pain in the fingers, arms, chest, legs, or toes that can be sudden and severe)
  • infections, such as blood infections, meningitis, or pneumonia
  • tiredness
  • swelling in the arms and legs
  • priapism (painful erection of the penis that lasts more than 4 hours)
  • stroke caused by blood clots that block blood flow to the brain
  • chest syndrome (blockage of small blood vessels in the lungs)
  • splenic sequestration (blockage of blood vessels in the spleen)

* If you have any of the above complications of SCD, it’s known as a sickle cell crisis.

Symptoms of SCD itself can include jaundice (a yellowing of the skin and the whites of the eyes), and pain and swelling in the hands and feet.

Effectiveness for sickle cell disease

Endari was studied in 230 people ages 5 to 58 years who had SCD. They had two or more pain crises within 12 months before starting the trial. People took either Endari or a placebo (a treatment with no active drug) twice daily for 48 weeks.

At the end of the trial, researchers compared the number of pain crises that occurred between the Endari and placebo groups. In addition, the number of visits to the hospital or emergency department for pain crisis was also assessed.

At 48 weeks, the following results were found:

People who took EndariPeople who took a placebo
Median* number of pain crises†34
Median number of hospitalizations for pain crisis in 48 weeks23
Median number of days in hospital6.511
Median number of days before having a pain crisis8454
Percentage of people who had chest syndrome8.6%23.1%

* “Median” means that at least half of the people in the study experienced this number of events.
† This includes chest syndrome, priapism, and splenic sequestration.

Over the 48 weeks, taking Endari reduced the average number of pain crises by 25% compared with a placebo.

Endari and children

The clinical trials that evaluated the safety and effectiveness of Endari included children ages 5 years and older. Therefore, Endari is considered to be just as safe and effective in children as in adults. For more information on Endari’s effectiveness, see the “Effectiveness for sickle cell disease” section above.

Endari can cause mild or serious side effects. The following lists contain some of the key side effects that may occur while taking Endari. These lists do not include all possible side effects.

For more information about the possible side effects of Endari, talk with your doctor or pharmacist. They can give you tips on how to deal with any side effects that may be bothersome.

Note: The Food and Drug Administration (FDA) tracks side effects of drugs it has approved. If you would like to notify the FDA about a side effect you’ve had with Endari, you can do so through MedWatch.

Mild side effects

Mild side effects* of Endari can include:

Most of these side effects may go away within a few days or a couple of weeks. But if they become more severe or don’t go away, talk with your doctor or pharmacist.

* This is a partial list of mild side effects from Endari. To learn about other mild side effects, talk with your doctor or pharmacist, or refer to Endari’s drug label information.
† For more information about this side effect, see “Side effect details” below.

Serious side effects

Serious side effects from Endari aren’t common, but they can occur. Call your doctor right away if you have serious side effects. Call 911 or your local emergency number if your symptoms feel life threatening or if you think you’re having a medical emergency.

Serious side effects and their symptoms can include:

* For more information about this side effect, see “Side effect details” below.

Side effects in children

Clinical studies that looked at side effects of Endari included children ages 5 years and older as well as adults. Therefore, it’s expected that children would have the same side effects as those reported for adults. No side effects were reported specifically for children.

Side effect details

You may wonder how often certain side effects occur with this drug, or whether certain side effects pertain to it.Here’s some detail on certain side effects this drug may cause.

Allergic reaction

As with most drugs, some people can have an allergic reaction after taking Endari. But it’s not known how often allergic reaction may have occurred in clinical studies.

Symptoms of a mild allergic reaction can include:

A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include:

  • swelling under your skin, typically in your eyelids, lips, hands, or feet
  • swelling of your tongue, mouth, or throat
  • trouble breathing

Call your doctor right away if you have an allergic reaction to Endari, as the reaction could become severe. Call 911 or your local emergency number if your symptoms feel life threatening or if you think you’re having a medical emergency.

Constipation

Constipation can occur while taking Endari. Clinical studies looked at people with sickle cell disease (SCD) who took Endari or a placebo twice daily for 48 weeks. (A placebo is a treatment with no active drug). Constipation occurred in:

  • 21% of people who took Endari
  • 18% of people who took a placebo

While taking Endari, if you feel that you’re passing stools less frequently or are having a hard time passing stools, talk with your doctor. They may be able to recommend ways to treat this side effect.

Pain

Some people have had pain in certain parts of the body when using Endari. This includes pain in the:

The percentages of people in clinical trials who had each type of pain are as follows:

People who took EndariPeople who took a placebo
Abdominal pain17%16%
Back pain12%5%
Chest pain12%8%
Arm and leg pain13%7%

If you have abdominal pain while taking Endari, talk with your doctor. They may want to see you to help determine whether the drug or something else is causing the pain.

You should also talk with your doctor if you have pain in your back, arms, or legs during your Endari treatment. They may be able to recommend ways to help you feel more comfortable.

In addition, if you have chest pain while using Endari, call 911 or your local emergency number right away. Chest pain may be sign of a more serious condition, including:

The Endari dosage your doctor prescribes will depend on your weight.

The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to fit your needs.

Drug forms and strengths

Endari comes in 5-gram (g) packets of powder that you can mix with certain foods or drinks and take by mouth.

Dosage for sickle cell disease

You’ll likely take Endari twice daily. The dose depends on your body weight. Here are the recommended dosages:

  • Less than 66 pounds (lb), or 30 kilograms (kg): A 5-g dose twice per day for a total of 10 g. You’ll use one packet of Endari per dose.
  • 66 lb to 143 lb (30 kg to 65 kg): A 10-g dose twice per day for a total of 20 g. You’ll use two packets of Endari per dose.
  • Greater than 143 lb (65 kg): A 15-g dose twice per day for a total of 30 g. You’ll use three packets of Endari per dose.

For each dose of Endari, you’ll mix the powder with either:

  • 8 ounces (oz) of cold or room temperature water, milk, or apple juice
  • 4 oz to 6 oz of food such as applesauce or yogurt

Then you’ll consume the drink or food. The powder doesn’t need to be completely dissolved in your drink or food before you take the dose.

Children’s dosage

Endari is approved for use in children ages 5 years and older. The drug is typically taken twice daily, and the dose depends on your child’s body weight. The dosage information is the same for adults and children. For more information, see “Dosage for sickle cell disease” right above.

Dosage questions

Below are answers to some questions you may have about taking Endari.

What if I miss a dose?

If you miss a dose of Endari, try to take the dose as soon as you remember. However, don’t double up your doses to make up for any missed ones.

To help make sure that you don’t miss a dose, try using a medication reminder. This can include setting an alarm on your phone or downloading a reminder app. A kitchen timer can work, too.

Will I need to use this drug long term?

Endari is meant to be used as a long-term treatment. If you and your doctor determine that Endari is safe and effective for you, you’ll likely take it long term.

You may wonder how Endari compares with other medications that are prescribed for similar uses. Here we look at how Endari and hydroxyurea are alike and different.

Ingredients

The active ingredient in Endari is L-glutamine.

Hydroxyurea is the active drug in Siklos, Hydrea, and Droxia.

Endari and hydroxyurea belong to different drug classes. A drug class describes a group of medications that work in a similar way. Endari is a type of medication called an amino acid. Hydroxyurea is in a class of medications called antineoplastic agents.

Uses

Here is a list of conditions that the Food and Drug Administration (FDA) has approved Endari and hydroxyurea to treat.

  • Endari is FDA-approved to:
    • Reduce the number of sudden complications of sickle cell disease (SCD) and how severe they are. These complications can include a pain crisis, which is severe pain across the body. Endari is approved for use in adults as well as children ages 5 years and older.
  • Hydroxyurea (Siklos, Droxia) is FDA-approved to:
    • Decrease the number of pain crises and the need for blood transfusions in people with SCD. For this purpose, the people must have moderate to severe pain crises that keep returning. Siklos is approved for use in adults as well as children ages 2 years and older. Droxia is approved for use in adults.

Drug forms and administration

Endari comes as a powder that you mix with certain foods or drinks and take by mouth. You’ll likely take the drug twice daily.

Hydroxyurea comes as a capsule or tablet that you take by mouth. You’ll likely take the drug once daily.

Side effects and risks

Endari and hydroxyurea are both used to ease certain complications related to SCD. Therefore, these medications can cause very similar side effects, but some different ones as well. Below are examples of these side effects.

Mild side effects

These lists contain up to 10 of the most common mild side effects that can occur with either Endari or hydroxyurea, as well as mild side effects that both drugs may share.

Serious side effects

These lists contain examples of serious side effects that can occur with either Endari or hydroxyurea, as well as serious side effects that both drugs may share.

* Hydroxyurea is the active drug in Siklos and Droxia. Both Siklos and Droxia have boxed warnings regarding bone marrow suppression and cancer. A boxed warning is the strongest warning required by the FDA. Boxed warnings alert doctors and patients about drug effects that may be dangerous.

Effectiveness

Endari and hydroxyurea have different FDA-approved uses, but they’re both used to ease complications in people who have SCD.

These drugs haven’t been directly compared in clinical studies, but studies have found both Endari and hydroxyurea to be effective for treating SCD.

Endari and hydroxyurea can also be used together to further ease complications of SCD. For example, in a clinical trial of Endari, 66% of people enrolled were already taking hydroxyurea before the study started. They kept taking hydroxyurea throughout the study while taking Endari or a placebo (a treatment with no active drug).

Costs

According to estimates on WellRx.com, the costs of Endari and hydroxyurea may vary depending on your treatment plan. The actual price you’ll pay for either drug depends on your insurance plan, your location, and the pharmacy you use.

Endari is a brand-name drug. It doesn’t have a generic form.

Hydroxyurea is a generic drug. It’s available as the brand-name drugs Siklos, Hydrea, and Droxia.

Brand-name medications usually cost more than generics.

Other drugs are available that can treat your condition. Some may be a better fit for you than others. If you’re interested in finding an alternative to Endari, talk with your doctor. They can tell you about other medications that may work well for you.

Note: Some of the drugs listed here are used off-label to treat these specific conditions. Off-label drug use means using a drug for a purpose other than what it’s been approved for by the Food and Drug Administration (FDA.)

Alternatives for sickle cell disease

Examples of other drugs that may be used to ease complications of sickle cell disease include:

Endari is approved to reduce the number of sudden complications of sickle cell disease (SCD) and how severe they are.

Sickle cell disease explained

SCD is an inherited disease that causes red blood cells (RBC) to change shape. The cells become curved like a C (similar to a sickle) instead of staying disc shaped. This can cause the RBCs to get stuck in blood vessels and block normal blood flow.

Red blood cells carry oxygen throughout the body. When blood and oxygen can’t easily get to some parts of the body, this can cause tissue damage and pain. This is called a pain crisis, which is an episode of severe pain across the body.

Examples of other SCD complications include chest syndrome (blockage of small blood vessels in the lung), blood clots, and stroke.

What Endari does

The mechanism of action of Endari is not fully understood. A mechanism of action is how a drug acts to cause an effect in the body.

Endari is an amino acid called L-glutamine. Amino acids make up proteins and are considered to be the building blocks of cells. It’s thought that Endari helps make antioxidants to protect sickle-shaped red blood cells from further damage.

How long does it take to work?

How long Endari takes to work to reduce complications of SCD varies from person to person. For example, your doctor can assess if and how fast the drug is working by looking at whether your pain has lessened. They can also see if you’re less short of breath and have reduced chest pain over time.

It is possible that your doctor may prescribe Endari for you with another medication used to treat sickle cell disease. They may do this to further help ease complications of SCD.

An example of such a medication is hydroxyurea (Droxia, Siklos).

In clinical studies of Endari, some people took hydroxyurea (Droxia, Siklos). Those who were stable on their dose for at least 3 months kept taking hydroxyurea while being treated with Endari.

If you have questions about whether it’s safe for you to take Endari with other medications, talk with your doctor or pharmacist.

It’s not known whether Endari interacts with alcohol. However, drinking too much alcohol can cause you to become dehydrated, which may lead to a pain crisis (an episode of severe pain) if you have sickle cell disease.

If you have questions about whether it’s safe for you to drink alcohol while taking Endari, talk with your doctor.

There aren’t any known interactions between Endari and other medications, herbs, supplements, or foods. This is because there haven’t been any studies of drug interactions with Endari.

However, to be safe, talk with your doctor and pharmacist before taking Endari. Tell them about all prescription, over-the-counter, and other drugs you take. Also tell them about any vitamins, herbs, and supplements you use. Sharing this information can help you avoid potential interactions.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

As with all medications, the cost of Endari can vary. To find current prices for Endari in your area, check out WellRx.com.

The cost you find on WellRx.com is what you may pay without insurance. The actual price you’ll pay depends on your insurance plan, your location, and the pharmacy you use.

It’s important to note that you’ll have to get Endari at a specialty pharmacy. This type of pharmacy is authorized to carry specialty medications. These are drugs that may be expensive or may require help from healthcare professionals to be used safely and effectively.

Before approving coverage for Endari, your insurance company may require you to get prior authorization. This means that your doctor and insurance company will need to communicate about your prescription before the insurance company will cover the drug. The insurance company will review the prior authorization request and decide if the drug will be covered.

If you’re not sure if you’ll need to get prior authorization for Endari, contact your insurance company.

Financial and insurance assistance

If you need financial support to pay for Endari, or if you need help understanding your insurance coverage, help is available.

Emmaus Medical, Inc., the manufacturer of Endari, offers a copay assistance program. For more information and to find out if you’re eligible for support, call 855-723-5646 or visit the program website.

Generic version

Endari isn’t available in a generic form. A generic drug is an exact copy of the active drug in a brand-name medication. Generics tend to cost less than brand-name drugs.

You should take Endari according to your doctor’s or healthcare provider’s instructions.

Endari comes as a powder. You should mix it with either of the following:

  • 8 ounces (oz) of cold or room-temperature water, milk, or apple juice
  • 4 oz to 6 oz of food, such as applesauce or yogurt

Then you’ll consume the drink or food. It’s not important for Endari to dissolve completely before you take it. However, make sure to take Endari right after mixing it with your drink or food.

When to take

Endari is typically taken twice daily. You can take it at any time during the day.

To help make sure that you don’t miss a dose, try using a medication reminder. This can include setting an alarm on your phone or downloading a reminder app. A kitchen timer can work, too.

Taking Endari with food

To take Endari, you’ll mix it with certain foods or drinks. For details, see “How to take Endari” above.

You can take Endari without regard to meals.

It’s not known whether it’s safe to take Endari during pregnancy.

If you’re pregnant or planning to become pregnant, talk with your doctor before taking Endari. They can review the pros and cons of the medication with you.

It’s not known if Endari is safe to take during pregnancy. If you’re sexually active and you or your partner can become pregnant, talk with your doctor about your birth control needs while you’re using Endari.

For more information about taking Endari during pregnancy, see the “Endari and pregnancy” section above.

It’s not known whether it’s safe to breastfeed while taking Endari. This is because it’s not known whether Endari passes into breast milk or how it can affect a breastfeeding child.

If you’re breastfeeding or planning to breastfeed, talk with your doctor before taking Endari. They can review the drug’s risks and benefits with you.

Here are answers to some frequently asked questions about Endari.

Will Endari cure my sickle cell disease?

No, Endari won’t cure sickle cell disease. Currently, there isn’t a cure for SCD.

However, Endari is approved to ease complications in people who have SCD. For information on Endari effectiveness for SCD, please see the “Endari for sickle cell disease” section above.

If you have questions about using Endari for SCD, talk with your doctor.

Can I have blood transfusions during my Endari treatment?

Yes. You should be able to have blood tranfusions while you take Endari. During clinical trials, some people who took Endari also received blood transfusions.

Blood transfusions may sometimes be needed if you have certain complications. These include stroke, organ failure, severe anemia, or an enlarged spleen.

If you have questions about having a blood transfusion while taking Endari, talk with your doctor.

Why do I have to get Endari at a specialty pharmacy?

Endari is available only at specialty pharmacies because it’s a specialty medication. These are drugs used to treat complicated or rare conditions, such as sickle cell disease.

Specialty pharmacies can provide support services for your medication. For example, many of the pharmacies have healthcare providers who can monitor your health status. Some specialty pharmacies can also offer patient education to help you take your medications safely and stay on track with them.

To find a specialty pharmacy near you, you can use this pharmacy locator.

Should I take Endari with food or something to drink?

Yes. You should mix Endari powder with either of the following:

  • at least 4 ounces (oz) to 6 oz of food, such as applesauce or yogurt
  • 8 oz of liquid, such as water or milk

Endari should be taken right after mixing. Endari doesn’t have to fully dissolve before you can take it. For more information on how to take Endari, see the “How to take Endari” section above.

This drug comes with several precautions. Before taking Endari, talk with your doctor about your health history. Endari may not be right for you if you have certain medical conditions or other factors affecting your health. These include:

  • Allergic reaction. If you’ve had an allergic reaction to Endari or any of its ingredients, you shouldn’t take Endari. Ask your doctor what other medications are better options for you.
  • Pregnancy. It’s not known whether Endari is safe to take while pregnant. For more information, see the “Endari and pregnancy” section above.
  • Breastfeeding. It’s not known whether it’s safe to breastfeed while taking Endari. For more information, see the “Endari and breastfeeding” section above.

Note: For more information about the potential negative effects of Endari, see the “Endari side effects” section above.

Using more than the recommended dosage of Endari can lead to serious side effects. Do not use more Endari than your doctor recommends.

What to do in case of overdose

Do not take more Endari than your doctor recommends. For some drugs, doing so may lead to unwanted side effects or overdose.

When you get Endari from the pharmacy, the pharmacist will add an expiration date to the label on the package. This date is typically 1 year from the date they dispensed the medication.

The expiration date helps guarantee that the medication is effective during this time. The current stance of the Food and Drug Administration (FDA) is to avoid using expired medications. If you have unused medication that has gone past the expiration date, talk to your pharmacist about whether you might still be able to use it.

Storage

How long a medication remains good can depend on many factors, including how and where you store the medication.

You should store Endari packets at room temperature (68°F to 77°F/20°C to 25°C) in a tightly sealed container away from light. Avoid storing this medication in areas where it could get damp or wet, such as bathrooms.

Disposal

If you no longer need to take Endari and have leftover medication, it’s important to dispose of it safely. This helps prevent others, including children and pets, from taking the drug by accident. It also helps keep the drug from harming the environment.

This article provides several useful tips on medication disposal. You can also ask your pharmacist for information about how to dispose of your medication.

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.