AQVESME

The population pharmacokinetic model simulated C max , C trough , AUC 0-12 and accumulation ratio of mitapivat at the recommended dosage is listed in Table 3.

Table 3Steady State Mitapivat Exposure at the Recommended Dosage a Mitapivat Dosage C max (ng/mL) C trough (ng/mL) AUC 0-12 (ng*h/mL) Accumulation Ratio 100 mg twice daily b 1641.7 (12.9%) 71 (18.5%) 4835.6 (5.8%) 0.83 a Pharmacokinetic parameters are presented as geometric mean (CV%). The interval of the last 12 hours was selected for s...

Patients with Transfusion-Dependent and Non-Transfusion-Dependent alpha- or beta-Thalassemia Transfusion-Dependent alpha- or beta-Thalassemia The efficacy of AQVESME was evaluated in ENERGIZE-T, a multinational, randomized, double-blind, placebo-controlled clinical study (NCT04770779) of 258 adult patients with transfusion-dependent alpha- or beta-thalassemia, defined as having had 6 to 20 RBC units transfused and no longer than a 6-week transfusion-free period during the 24 weeks prior to randomization. Patients were included if they had a documented diagnosis of thalassemia (beta-thalassemia...

The following clinically significant adverse reaction is described elsewhere in labeling: Hepatocellular Injury [see Warnings and Precautions (5.1) ]. The most common adverse reactions were headache and insomnia. ( 6.1 ) 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. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in...

None. None. ( 4 )

5.1 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...

7 DRUG INTERACTIONS Strong CYP3A Inhibitors and Inducers: Avoid concomitant use. ( 7.1 ) Moderate CYP3A Inhibitors: Avoid concomitant use. ( 7.1 ) Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, see Full Prescribing Information for recommended dosage for drug interactions with moderate CYP3A inducers. ( 2.4 , 7.1 ) Sensitive CYP3A substr...