Detailed instructions and usage of mitapivat sulfate-Pyrukynd

1. Common name: mitapivat

Product name: Pyrukynd

Other names: Mitapiva sulfate, Mitapivat

2. Indications:

Mitapivat-Pyrukynd is indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.

3. Usage and dosage:

1. How to take: Swallow the tablet whole. Do not break, crush, chew or dissolve. It can be taken with food or on an empty stomach.

2. Recommended dose: The starting dose of Pyrukynd is 5 mg, taken orally twice a day. To gradually increase hemoglobin (Hb), titrate pyruvate from 5 mg twice daily to 20 mg twice daily and then to the maximum recommended dose of 50 mg twice daily, increasing the dose every 4 weeks. Before increasing to the next dose level, assess Hb and transfusion requirements as some patients may achieve and maintain normal Hb at 5 mg twice daily or 20 mg twice daily.

1) The first1-4 weeks: 5mg, twice daily;

2) Weeks 5-8: If hemoglobin is lower than the normal range or blood transfusion is required within the past 8 weeks, the dose is increased to 20 mg twice daily. If hemoglobin is within the normal range and transfusions have not been required within the past 8 weeks, the dose is maintenance 5 mg twice daily.

3) Weeks 9-12: If hemoglobin is below the normal range or blood transfusion is required within the past 8 weeks, the dose is increased to 50 mg twice daily (maximum recommended dose). If hemoglobin is within the normal range and transfusions have not been required within the past 8 weeks, maintain the current dose (5 mg or 20 mg twice daily).

If no efficacy is observed after 24 weeks of treatment (based on hemoglobin, hemolysis indicators and blood transfusion requirements), use should be discontinued.

3. Missed dose: If the missed dose does not exceed 4 hours, the dose should be taken as soon as possible; If the missed dose exceedsAfter 4 hours, skip this dose and take the medicine normally at the next scheduled time.

4. Adverse reactions:

In clinical studies of Pyrukynd, the most common adverse reactions included laboratory abnormalities (≥10%) including decreased estrone (men), increased urate, back pain, decreased estradiol (men) and joint pain.

5. Supply and storage:

Metapival may be stored 20°C to 25°C (68°F to 77°F), with a tolerance of 15°C to 30°C (59°F to 86°F).

6. Special groups:

1. Pregnancy: The available data from clinical trials of Pyrukynd are insufficient to assess drug-related risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

2. Untreated PK deficiency in pregnant women may lead to acute hemolysis, premature delivery, miscarriage and severe anemia, requiring frequent blood transfusions. Additionally, preeclampsia and severe hypertension have been reported.

3. Renal impairment: Pyrukynd undergoes extensive hepatic metabolism. Moderate and severe hepatic impairment are expected to increase systemic exposure of mitapival. Pyrukynd should be avoided in patients with moderate and severe hepatic impairment.

7. Mechanism of action:

Metapival is a pyruvate kinase activator that acts by allosterically binding to the pyruvate kinase tetramer and increasing pyruvate kinase (PK) activity. The red blood cell (RBC) form of pyruvate kinase (PK-R)mutates inPK deficiency, resulting in reduced adenosine triphosphate (ATP), shortened RBC lifespan, and chronic hemolysis.

8. Listing situation:

Original drug:

United States: 2022-02-17, approved for marketing (trade name: Pyrukynd)

EU: 2022-11-09, approved for marketing (trade name: Pyrukynd)

China: Not yet listed

Reference materials:https://www.ema.europa.eu/en/medicines/human/EPAR/pyrukynd