PYRUKYND (mitapivat sulfate)

Mitapivat exposure increased in an approximately dose proportional manner over the clinically relevant dose range of 5 mg to 50 mg twice daily. The population pharmacokinetic model simulated Cmax, Ctrough, AUC0-12 and accumulation ratio of mitapivat at recommended dosages are listed in the table below.

Table 5Steady State Mitapivat Exposure at Recommended Dosages a Mitapivat Dosage C max (ng/mL) C trough (ng/mL) AUC 0-12 (ng*h/mL) Accumulation Ratio 5 mg twice daily 101.2 (17%) 10.1 (74%) 450....

Patients with PK Deficiency Patients Not Regularly Transfused The efficacy of PYRUKYND was evaluated in ACTIVATE, a multinational, randomized, double-blind, placebo-controlled clinical study (NCT03548220) of 80 adults with PK deficiency who were not regularly transfused, defined as having had no more than 4 transfusions in the 52- week period prior to treatment and no transfusions in the 3-month period prior to treatment. Patients were included if they had documented presence of at least 2 variant alleles in the pyruvate kinase liver and red blood cell (PKLR) gene, of which at least 1 was a mi...

The following clinically significant adverse reaction is described elsewhere in labeling: Acute Hemolysis with Abrupt Treatment Discontinuation [see Warn ings and Preca utions (5.1) ]. Hepatocellular Injury in Another Condition [see Warnings and Precautions (5.2) ] . The most common adverse reactions including laboratory abnormalities (≥ 10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia. ( 6.1 ) To report S...

None None ( 4 )

Acute Hemolysis: Avoid abrupt interruption or abrupt discontinuation of PYRUKYND to minimize the risk of acute hemolysis. A gradual reduction in dosing rather than abrupt cessation is recommended when possible. ( 5.1 ) Hepatocellular Injury in Another Condition: Obtain liver tests prior to the initiation of PYRUKYND and monthly thereafter for the first 6 months and as clinically indicated. Interrupt PYRUKYND if clinically significant increases in liver tests are observed or alanine aminotransfer...

7 DRUG INTERACTIONS Strong CYP3A Inhibitors and Inducers: Avoid concomitant use. ( 7.1 ) Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily. ( 7.1 ) Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage. ( 7.1 ) Sensitive CYP3A, CYP2B6, CYP2C substrates including hormonal contraceptives: Avoid co...