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FDA issued a safety announcement on November 29, 2018, that symptoms of differentiation syndrome are not being recognized in patients receiving enasidenib for the treatment of acute myeloid leukemia (AML). Enasidenib is labeled to treat AML in patients with a specific isocitrate dehydrogenase‑2 mutation who have not improved or progressed with other chemotherapies. Enasidenib carries a Boxed Warning for risk of differentiation syndrome. FDA became aware of cases where symptoms went unrecognized and patients did not received treatment. Symptoms can begin anywhere from 10 days to 5 months after starting treatment and may include unexplained:
- Bone pain
- Cough or shortness of breath
- Dizziness
- Fever
- Rapid weight gain (10 lbs or more in 1 week)
- Swelling of extremities, groin, neck, or underarm
Health care providers should provide a Medication Guide to patients and discuss signs and symptoms of differentiation syndrome when starting therapy and at each follow-up visit. Consider a diagnosis of differentiation syndrome if a patient experiences any unexplained symptoms. In addition to the symptoms above, differentiation syndrome can result in:
- Acute respiratory distress
- Hepatic, renal, or multiorgan dysfunction
- Lymphadenopathy
- Pleural effusion
- Pericardial effusion
Differentiation syndrome can be life-threatening or fatal. Treat promptly with intravenous or oral corticosteroids and do not taper until symptoms are completely resolved. Continue to monitor patients and provide additional care as needed. Hold enasidenib treatment if renal dysfunction or severe pulmonary dysfunction requiring intubation for longer than 48 hours occur. Do not restart therapy until symptoms are no longer severe.
Patients should contact a health care professional or go to a hospital emergency room immediately if they develop signs and symptoms of differentiation syndrome.
Report adverse events with enasidenib or other medications to the FDA MedWatch program.
- FDA Drug Safety Report link:
www.fda.gov/downloads/Drugs/DrugSafety/UCM626958.pdf - MedWatch Safety Report link:
www.fda.gov/Drugs/DrugSafety/ucm626923.htm