Active Ingredient: Mitapivat
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 5 milligrams mitapivat, 2 times daily, over the duration of 4 weeks. Afterwards, oral, 20 milligrams mitapivat, 2 times daily, over the duration of 4 weeks. Afterwards, oral, 50 milligrams mitapivat, 2 times daily, over the duration of 4 weeks.
The recommended starting dose is 5 mg taken orally twice daily.
To gradually increase haemoglobin (Hb) levels and maximise the effect, mitapivat should be titrated through sequential doses of 5 mg twice daily, 20 mg twice daily and 50 mg twice daily, with sequential dose increases occurring every 4 weeks (see Table 1). Hb level and transfusion requirement should be assessed before increasing to the next dose level as some patients may reach and maintain normal Hb levels at 5 mg twice daily or 20 mg twice daily. The maximum recommended dose is 50 mg twice daily.
Treatment with mitapivat is intended to be long-term. Mitapivat should be discontinued if a patient does not experience an improvement of haemolytic anaemia at the maximum recommended dose, based on the totality of laboratory results and clinical status of the patient, unless there is another explanation for response failure (e.g. bleeding, surgery, other concomitant illnesses).
Table 1. Dose titration and maintenance schedule:
| Duration | Dose titration and maintenance |
|---|---|
| Day 1 to Week 4 | All patients: • 5 mg twice daily |
| Week 5 to Week 8 | If Hb level is below normal range or patient has required a transfusion within the last 8 weeks: • Increase to 20 mg twice daily and maintain for 4 weeks. If Hb level is within normal range and patient has not required a transfusion within the last 8 weeks: • Maintain 5 mg twice daily. |
| Week 9 to Week 12 | If Hb level is below normal range or patient has required a transfusion within the last 8 weeks: • Increase to 50 mg dose twice daily and maintain thereafter. If Hb level is within normal range and patient has not required a transfusion within the last 8 weeks: • Maintain current dose (5 mg twice daily or 20 mg twice daily). |
| Maintenance | If Hb level decreases, consider up-titration to the maximum of 50 mg twice daily as per the above schedule. |
To minimise the risk of acute haemolysis, abrupt interruption or discontinuation of mitapivat should be avoided. The dose should be tapered to gradually discontinue the medicinal product over a 1-2 week period (see Table 2). Patients should be monitored for signs of acute haemolysis with worsening of anaemia.
Table 2. Dose taper schedule:
| Current dose | Dose taper schedule | ||
|---|---|---|---|
| Day 1-7 | Day 8-14 | Day 15 | |
| 5 mg twice daily | 5 mg once daily | Discontinue | N/A |
| 20 mg twice daily | 20 mg once daily | 5 mg once daily | Discontinue |
| 50 mg twice daily | 50 mg once daily | 20 mg once daily | Discontinue |
N/A: not applicable.
If a dose of mitapivat is missed by 4 hours or less, the dose should be administered as soon as possible. If a dose is missed by more than 4 hours, a replacement dose should not be administered, and the patient should wait until the next scheduled dose. Subsequently, the patient should return to their normal dosing schedule.
If a dose reduction is required for adverse event management and/or tolerability, the dose may be reduced to the next lower dose level, 20 mg twice daily or 5 mg twice daily.
If a patient needs to discontinue the medicinal product due to an adverse event, the dose taper schedule (Table 2) should be followed. In situations where the risk to the patient due to the adverse event is greater than the risk of acute haemolysis due to sudden withdrawal of the medicinal product, treatment may be stopped without taper and patients should be monitored for signs of acute haemolysis with worsening of anaemia.
There are limited data available in elderly patients. No dose modifications are recommended in elderly patients.
It may be taken with or without food.
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