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Idhifa

enasidenib
Used for Leukemia
Used for Leukemia

Idhifa (enasidenib) is a targeted therapy used to treat acute myeloid leukemia (AML). But Idhifa (enasidenib) is only for adults who've a specific mutation in the IDH2 protein. This medication is taken by mouth, typically once daily. It can cause side effects such as nausea, diarrhea, and a serious condition called differentiation syndrome.

Reviewed by:
reviewer
Allison Baxley, PharmD, BCOP
reviewer
Connie Zheng, PharmD
Last reviewed on September 22, 2023
BasicsSide effectsPros & consPharmacist tipsFAQsWarningsDosageReferencesPricesMedicare
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What is Idhifa (enasidenib)?

What is Idhifa (enasidenib) used for?

How Idhifa (enasidenib) works

Acute myeloid leukemia (AML) is caused by gene changes (mutation) that prevent immature blood cells from developing into healthy cells. Instead, these cells turn into cancer cells. Some people with AML have a mutation in the gene that makes the isocitrate dehydrogenase 2 (IDH2) protein.

Idhifa (enasidenib) is an IDH2 inhibitor. When Idhifa (enasidenib) blocks IDH2, it lowers the number of cancer cells and allows the young blood cells to mature into healthy cells .

Drug Facts

Common BrandsIdhifa
Drug ClassIDH2 Inhibitor
Controlled Substance ClassificationNot a controlled medication
Generic StatusNo lower-cost generic available
AvailabilityPrescription only
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What are the side effects of Idhifa (enasidenib)?

The following side effects may get better over time as your body gets used to the medication. Let your healthcare provider know immediately if you continue to experience these symptoms or if they worsen over time.

Common Side Effects

Other Side Effects

Serious Side Effects

Contact your healthcare provider immediately if you experience any of the following.
  • Differentiation syndrome: fever, sudden weight gain, trouble breathing, chest pain, swelling in legs

Source: DailyMed

The following side effects have also been reported

Side effects that you should report to your care team as soon as possible:

  • Allergic reactions—skin rash, itching, hives, swelling of the face, lips, tongue, or throat
  • Fever, cough, dizziness, feeling faint or lightheaded, shortness of breath, bone pain, sudden weight gain, swelling of the ankles, hands, or feet, which may be signs of differentiation syndrome
  • High white blood cell level—fever, fatigue, trouble breathing, night sweats, change in vision, weight loss
  • Liver injury—right upper belly pain, loss of appetite, nausea, light-colored stool, dark yellow or brown urine, yellowing skin or eyes, unusual weakness or fatigue
  • Tumor lysis syndrome (TLS)—nausea, vomiting, diarrhea, decrease in the amount of urine, dark urine, unusual weakness or fatigue, confusion, muscle pain or cramps, fast or irregular heartbeat, joint pain

Side effects that usually do not require medical attention (report these to your care team if they continue or are bothersome):

pros-and-cons

Pros and cons of Idhifa (enasidenib)

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Pros

Taken by mouth, so good for people who don’t like needles

Recommended treatment for certain people with AML and an IDH2 mutation

Works in a more specific, targeted way than traditional chemotherapy

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Cons

Might interact with other oral medications, such as birth controls

Can’t be used in people who don’t have an IDH2 mutation

Can cause a serious side effect called differentiation syndrome

pharmacist-tips

Pharmacist tips for Idhifa (enasidenib)

pharmacist

  • Based on animal studies, there’s a possibility that taking Idhifa (enasidenib) might affect your fertility. In other words, it may make it more difficult for you to have children. If you’re concerned about being able to have children in the future, talk to your provider before starting Idhifa (enasidenib).

    • Check your body temperature regularly, ideally once a day. Call your provider immediately if your temperature is 100.4 degrees Fahrenheit or higher; this means you have a fever. Sometimes a fever might be the only sign that you’re sick.

      • Take Idhifa (enasidenib) around the same time each day. You can take it with or without food, but make sure to take the tablets whole and do not crush or split them. If you miss a dose and remember that same day, go ahead and take it. If you miss a dose and it’s already the next day, just skip it and start with your next scheduled dose.

        • Females who are taking Idhifa (enasidenib)] should avoid breastfeeding during treatment and for 2 months after the last dose. We don’t know whether Idhifa (enasidenib)] is found in breast milk and whether it affects breastfed babies, but there’s a possible risk of harm to a baby.

          • It’s possible that Idhifa (enasidenib) can cause hormonal birth control pills not work as well. If you’re a female able to have children, talk to your provider about which birth control is best for you. Your provider might recommend a non-hormonal birth control option.

            • Ask your provider about the best way to handle and throw away Idhifa (enasidenib) safely. Anticancer medications can be harmful to people who handle or come in contact with them. You should store the medication up and away, so children and pets won’t be able to reach it.

              • You might experience some diarrhea when you first start Idhifa (enasidenib) treatment, but this should improve over time. Your provider might suggest an over-the-counter medication, like loperamide (Imodium A-D), to help manage diarrhea. If you have diarrhea, it’s important to drink a lot of fluids to stay hydrated and to replace the liquids you've lost. But try to avoid sugary sports drinks because they can make diarrhea worse.

                faqs

                Frequently asked questions about Idhifa (enasidenib)

                Is Idhifa (enasidenib) chemotherapy?
                No, Idhifa (enasidenib) is not a chemotherapy medication. Chemotherapy works by attacking cells that are growing quickly. Idhifa (enasidenib) works in a more specific way, and because of that is called a type of targeted therapy. It targets and blocks a specific protein called IDH2. As a result, leukemia cells aren’t able to grow and spread as well.
                Can I take Idhifa (enasidenib) if I don’t have an IDH2 mutation?
                No, your provider won’t prescribe Idhifa (enasidenib) if you don’t have an IDH2 mutation. Because Idhifa (enasidenib) is a targeted therapy, it only targets and blocks the IDH2 protein. If your AML doesn’t have a problem with the IDH2 protein, then Idhifa (enasidenib) won’t work well to treat the cancer. Before you start treatment for AML, your provider will take a sample of the cancer to check it for any specific mutations. Based on the test results, your provider can talk with you about treatment options that would work best for you.
                Why do I need to monitor my temperature regularly while taking Idhifa (enasidenib)?
                When you have AML, typically this means your white blood cells don’t work as well to help fight against infections. This can be true even after you start taking Idhifa (enasidenib). As a result, you’re more likely to get sick. And sometimes, fever is the only symptom you’ll have when you’re sick. Your body might not show other signs of infection, like chills or body aches. It’s important to detect infection early, and checking for a fever is one of the best ways to do this. If you have a temperature of 100.4 degrees Fahrenheit or higher, contact your provider right away.
                Does Idhifa (enasidenib) cause nausea and vomiting?
                Some people taking Idhifa (enasidenib) can experience nausea and vomiting, but it’s usually not severe. To prevent nausea, your provider might recommend that you take an antiemetic, such as ondansetron (Zofran), before you take your Idhifa (enasidenib) dose. They might also recommend other medications to either take with your Idhifa (enasidenib) dose, or to take in between doses. If you have nausea and your current medications aren’t helping, contact your provider.
                What is differentiation syndrome and why might Idhifa (enasidenib) cause it?
                Differentiation syndrome is a immune reaction that some people experience after taking Idhifa (enasidenib). It’s thought to happen because many young blood cells grow into mature blood cells at the same time. These changes sometimes trigger an immune-related response that can cause tissue damage and inflammation in multiple parts of the body. Symptoms of differentiation syndrome can include fever, trouble breathing, weight gain, chest pain, and bone pain. This reaction is a medical emergency and it must be treated right away. Treatment typically involves corticosteroids, such as dexamethasone. Sometimes you might also require medications to help keep your blood pressure in a normal range. Most people can restart Idhifa (enasidenib) once differentiation syndrome has gotten better.
                What is tumor lysis syndrome?
                Tumor lysis syndrome is a side effect that some people experience after taking Idhifa (enasidenib). It occurs when cancer cells are destroyed and release what was inside them into the bloodstream. This can be dangerous because it can lead to high levels of potassium and uric acid in the blood, which can cause problems with your heart and kidneys. Tumor lysis syndrome is most common in cancers such as lymphoma, leukemia, and multiple myeloma. Because Idhifa (enasidenib) works to kill leukemia cancer cells, it’s possible for tumor lysis syndrome to happen while you’re taking it. Your provider will monitor you closely when you start Idhifa (enasidenib). They also might recommend other medications like allopurinol (Zyloprim) to prevent complications.
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                What are the risks and warnings for Idhifa (enasidenib)?

                Idhifa (enasidenib) can cause some serious health issues. This risk may be even higher for certain groups. If this worries you, talk to your doctor or pharmacist about other options.

                risk-warning

                Differentiation syndrome

                Some people taking Idhifa (enasidenib) experienced a serious immune reaction called differentiation syndrome. This side effect can happen up to 5 months after starting treatment, but sometimes as early as after the first dose. Differentiation syndrome is a medical emergency and must be treated right away. Treatment typically involves corticosteroids, such as dexamethasone. Sometimes you might also require medications to help keep your blood pressure in a normal range. If you have any of the symptoms of differentiation syndrome, including fever, trouble breathing, rapid weight gain, chest pain, bone pain, and low blood pressure, seek medical attention right away.

                risk-warning

                Harm to unborn baby

                Based on animal studies, Idhifa (enasidenib) might harm an unborn baby or raise the risk for miscarriage (pregnancy loss). Because of these risks, if you’re a female who can get pregnant, you should use birth control while taking Idhifa (enasidenib) and for 2 months after the last dose. Your provider might require a negative pregnancy test before you start treatment. Let your provider know right away if you become pregnant while taking Idhifa (enasidenib).

                If you’re a male who's sexually active with a partner who can get pregnant, you should use condoms while taking Idhifa (enasidenib) and for 2 months after the last dose.

                dosage

                Idhifa (enasidenib) dosage forms

                Typical dosing for Idhifa (enasidenib)

                The typical dose is 100 mg by mouth once a day.

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                References

                Best studies we found

                Adeyinka, A., et al. (2022). Tumor lysis syndrome. StatPearls.

                American Cancer Society. (2019). Chemotherapy safety.

                American Cancer Society. (2020). Fever.

                View All References (19)

                American Cancer Society. (2021). How targeted therapies are used to treat cancer.

                American Cancer Society. (2022). Biomarker tests and cancer treatment.

                American Cancer Society. (2023). Targeted therapy drugs for acute myeloid leukemia (AML).

                Celgene Corporation. (2023). Idhifa- enasidenib mesylate tablet, film coated [package insert]. DailyMed.

                Fathi, A. T., et al. (2018). Differentiation syndrome associated with enasidenib, a selective inhibitor of mutant isocitrate dehydrogenase 2: Analysis of a phase 1/2 study. Journal of the American Medical Association Oncology.

                Howard, S. C., et al. (2011). The tumor lysis syndrome. The New England Journal of Medicine.

                Issa, G. C., et al. (2021). Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm. Blood Cancer Journal.

                Leukemia and Lymphoma Society. (n.d.). Relapsed and refractory.

                Leukemia and Lymphoma Society. (n.d.). Side effects.

                Logan, C., et al. (2020). Updates in infection risk and management in acute leukemia. Hematology, American Society of Hematology Education Program.

                MedlinePlus. (2023). Phosphate in blood.

                Myers, R. A., et al. (2018). Enasidenib: An oral IDH2 inhibitor for the treatment of acute myeloid leukemia. Journal of the Advanced Practitioner in Oncology.

                National Cancer Institute. (2023). Acute myeloid leukemia treatment (PDQ®)–Patient version.

                National Comprehensive Cancer Network. (2022). Nausea and vomiting.

                National Comprehensive Cancer Network. (2023). Acute myeloid leukemia.

                Reed, D. R., et al. (2019). Enasidenib in acute myeloid leukemia: Clinical development and perspectives on treatment. Cancer Management and Research.

                Stein, E. M., et al. (2017). Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood.

                U.S. Food and Drug Administration. (2018). FDA warns that symptoms of a serious condition affecting the blood cells are not being recognized with the leukemia medicine Idhifa (enasidenib).

                Zeidner, J. F. (2020). Differentiating the differentiation syndrome associated with IDH inhibitors in AML. Clinical Cancer Research.

                GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.
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