mitapivat
Hepatocellular Injury
AQVESME can cause hepatocellular injury. Avoid use of AQVESME in patients with cirrhosis. In patients with thalassemia treated with AQVESME, liver injury with and without jaundice has been observed within the first 6 months of exposure. Obtain liver tests (including ALT, AST, alkaline phosphatase, total bilirubin with fractionation) prior to the initiation of AQVESME, then every 4 weeks for the first 24 weeks, and as clinically indicated thereafter. Interrupt AQVESME if clinically significant increases in liver tests are observed or alanine aminotransferase is >5 times the upper limit of normal (ULN). Complete a comprehensive evaluation to rule out other causes of liver injury when drug-induced liver injury (DILI) is suspected. Discontinue AQVESME if hepatocellular injury due to AQVESME is suspected.
Symptoms and signs of early liver injury may mimic those of thalassemia. Advise patients to report new or worsening symptoms of loss of appetite, nausea, right upper quadrant abdominal pain, vomiting, scleral icterus, jaundice, or dark urine while on AQVESME treatment.
During the double-blind period, 2 of 301 patients (0.66%) with thalassemia treated with AQVESME experienced adverse reactions suggestive of hepatocellular injury. Three additional patients experienced adverse reactions suggestive of hepatocellular injury during the open-label extension periods after switching from placebo to AQVESME. Of these 5 patients, two had serious liver injury and were hospitalized including 1 patient who developed jaundice (peak bilirubin 32 mg/dL). Another patient developed jaundice (peak bilirubin 4 mg/dL) without being hospitalized. These reactions were characterized by a time to onset within the first 6 months of treatment with peak elevations of alanine aminotransferase of >5×ULN with or without jaundice. All patients discontinued treatment with AQVESME, and these reactions improved upon treatment discontinuation.
AQVESME is available only through a restricted program under a REMS
Monitoring data
To report SUSPECTED ADVERSE REACTIONS, contact Agios Pharmaceuticals, Inc. at 1-833-228-8474 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
REMS
- Prescribers must be certified by enrolling in the REMS and completing training.
- Prescribers must counsel patients receiving AQVESME about the risk of hepatocellular injury.
- Prescribers must monitor liver tests (including ALT, AST, alkaline phosphatase, total bilirubin with fractionation, and other tests as clinically indicated) to determine if the patient is appropriate to receive AQVESME treatment.
- Patients must enroll in the REMS and comply with the monitoring requirements.
- Pharmacies must be certified by enrolling in the REMS and must only dispense to patients who are authorized to receive AQVESME.
- Further information is available at www.aqvesmerems.com or 1-800-625-9951.
Medical guidelines
Package inserts
Additional information
AQVESME (mitapivat) is approved for anemia in adults with alpha- or beta-thalassemia, and its FDA label includes a Boxed Warning for hepatocellular injury (serious liver injury).
PYRUKYND (mitapivat) is approved for hemolytic anemia in adults with pyruvate kinase (PK) deficiency and does not include a boxed warning in its FDA prescribing information.