PYRUKYND
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PYRUKYND (PYRUKYND).
PYRUKYND (mitapivat) is an oral, small-molecule activator of pyruvate kinase (PK). It binds to PK and increases its enzymatic activity, thereby improving glycolytic flux and ATP production in red blood cells. This reduces hemolysis and improves anemia in patients with pyruvate kinase deficiency.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C8; also undergoes glucuronidation via UGT1A1, UGT1A3, and UGT1A9. A minor metabolic pathway involves oxidation by aldehyde oxidase. |
| Excretion | Primarily metabolized, with <5% excreted unchanged in urine. No significant biliary/fecal elimination reported. |
| Half-life | Terminal half-life approximately 18 hours (range 14-22 h) in healthy volunteers; supports twice-daily dosing. |
| Protein binding | 99.9% bound; primarily to albumin. |
| Volume of Distribution | Approximately 0.2 L/kg, indicating limited extravascular distribution. |
| Bioavailability | Absolute bioavailability not determined; oral administration results in rapid absorption with high exposure. |
| Onset of Action | PK: peak plasma concentration at 2-3 hours; clinical effect on hemoglobin increase observed within 2-4 weeks of initiation. |
| Duration of Action | Hemoglobin elevation persists with continued dosing; trough concentrations maintain target >20% after 12 hours. |
50 mg orally once daily, taken with food; for patients with pyruvate kinase deficiency, dose may be increased to 100 mg once daily based on hemoglobin response and tolerability.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min); not studied in severe renal impairment (eGFR <30 mL/min) or dialysis, use caution. |
| Liver impairment | Child-Pugh A: no dose adjustment; Child-Pugh B: reduce dose to 50 mg once daily; Child-Pugh C: avoid use. |
| Pediatric use | Age ≥5 years: same dosing as adults based on body weight ≥18 kg; for <18 kg, no established dosing; safety and efficacy not established in children <5 years. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor renal function and tolerability due to potential age-related decline in renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PYRUKYND (PYRUKYND).
| Breastfeeding | No data on presence in human milk; M/P ratio unknown. Consider developmental and health benefits of breastfeeding along with mother’s clinical need and potential adverse effects on the breastfed child from PYRUKYND or underlying condition. |
| Teratogenic Risk | First trimester: No adequate human data; animal studies not available. Pyruvate kinase deficiency (PKD) itself may increase pregnancy risks. Second and third trimesters: Potential for maternal anemia worsening, leading to reduced fetal oxygenation and growth restriction. |
■ FDA Black Box Warning
None.
| Serious Effects |
None.
| Precautions | ["Acute hemolytic anemia: Monitor for signs of hemolysis and discontinue if hemolysis occurs.","Risk of gout/hyperuricemia: Monitor uric acid levels and manage appropriately.","Embryo-fetal toxicity: May cause fetal harm; advise females of reproductive potential to use effective contraception."] |
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| Fetal Monitoring |
| Monitor hemoglobin, hematocrit, reticulocyte count, and signs of hemolysis monthly during pregnancy; fetal growth ultrasound and nonstress testing in third trimester; assess for need for transfusions or early delivery if severe anemia develops. |
| Fertility Effects | No studies on fertility in humans; animal reproduction studies not available. Impact on fertility is unknown, but underlying PKD may affect fertility due to chronic anemia and iron overload. |