Skip to main content

Can Idhifa cause differentiation syndrome?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Sep 26, 2022.

Official answer


Yes, Idhifa (enasidenib) labeling contains a Boxed Warning, the most prominent warning issued from the FDA, about serious side effects due to differentiation syndrome.

In studies conducted by the manufacturer, 14% of patients treated with Idhifa experienced differentiation syndrome, which may be life-threatening or fatal if not treated.

Idhifa is an FDA-approved targeted treatment for acute myeloid leukemia (AML) that works by blocking the enzyme isocitrate dehydrogenase-2 (IDH2).

Blocking IDH2 helps immature blood cells in your bone marrow to mature into functioning red and white blood cells and platelets. These cells help to deliver oxygen to tissues, fight infection, and help prevent bleeding.

What is differentiation syndrome?

Differentiation syndrome is a condition that affects your immune system. It occurs due to a large, rapid release of cytokines (inflammatory immune proteins) due to the anticancer effect of the medicine on the leukemia cells.

  • The onset of differentiation syndrome has been seen from the first day of treatment with Idhifa until 5 months after treatment was started.
  • Differentiation syndrome can result in rapid expansion of myeloid cells (such as neutrophils, monocytes, and macrophages), all important components of the immune system.
  • Other drugs used to treat AML, such as Xospata (gilteritinib) and Tibsovo (ivosidenib), can also be associated with differentiation syndrome.

What are the symptoms of differentiation syndrome?

There is no diagnostic test for differentiation syndrome, so it is important to watch for symptoms.

Call your doctor or go to the nearest hospital emergency room right away if you develop any of the following symptoms of differentiation syndrome while taking Idhifa:

  • fever
  • cough
  • shortness of breath, trouble breathing
  • swelling of arms and legs
  • swelling around neck, groin, or underarm area
  • fast weight gain (more than 10 pounds within a week)
  • bone pain
  • low blood pressure

If you develop any of these symptoms of differentiation syndrome, your doctor may start you on a type of oral or intravenous (given through a vein) medicine called a corticosteroid (for example, dexamethasone). You may need to be monitored in the hospital. Differentiation syndrome can be fatal if not treated.

Bottom Line

  • The Idhifa (enasidenib) product labeling contains a Boxed Warning about serious side effects due to differentiation syndrome.
  • Differential syndrome occurs due to a large, rapid release of cytokines (inflammatory immune proteins) and can be life-threatening.
  • Learn about the symptoms of differentiation syndrome and call your doctor or get emergency treatment right away if you develop any of these symptoms.

This is not all the information you need to know about Idhifa for safe and effective use. Review the full Idhifa (enasidenib) information here, and discuss this information with your doctor or other health care provider.


Related medical questions

Drug information

Related support groups

  • Idhifa (4 questions, 3 members)