Mechanism of Action
Target the underlying cause of PK deficiency1,2
PYRUKYND® is an allosteric activator of pyruvate kinase (PK) that increases the activity of the PK enzyme, improving glycolytic function.1
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- PYRUKYND allosterically binds to the PK enzyme, improving enzyme stability and activity1-3
- Increased PK activity is believed to improve ATP production and increase RBC energy1-3*
- Lifespan of the RBC is extended, hemolysis is reduced, and anemia is improved1-3
ATP=adenosine triphosphate; PK=pyruvate kinase; RBC=red blood cell.
*PYRUKYND was shown to increase ATP in healthy volunteers.1
References: 1. PYRUKYND. Prescribing Information. Agios Pharmaceuticals, Inc.; 2022. 2. Rab MAE, van Oirschot BA, Kosinski PA, et al. AG-348 (mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2021;106(1):238-249. 3. Kung C, Hixon J, Kosinski PA, et al. AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency. Blood. 2017;130(11):1347-1356.
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.
Important Safety Information
Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.
Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, 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.
- Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
- Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
- Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
- Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
- UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
- P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.
Please see full Prescribing Information for PYRUKYND.