Drug Detail:Pyrukynd taper pack (Mitapivat [ mye-ta-piv-at ])
Generic Name: mitapivat 5mg
Dosage Form: tablet, film coated
Drug Class: Miscellaneous metabolic agents
Recommended Dosage
PYRUKYND is taken with or without food and swallowed whole. Do not split, crush, chew, or dissolve the tablets.
The starting dosage for PYRUKYND is 5 mg orally twice daily. To gradually increase hemoglobin (Hb), titrate PYRUKYND from 5 mg twice daily to 20 mg twice daily, and then to the maximum recommended dose of 50 mg twice daily, with these dose increases occurring every 4 weeks (see Table 1). Assess Hb and transfusion requirement before increasing to the next dose level, as some patients may reach and maintain normal Hb at 5 mg twice daily or 20 mg twice daily.
Discontinue PYRUKYND if no benefit has been observed by 24 weeks, based on the hemoglobin and hemolysis laboratory results and transfusion requirements.
| Duration | Dosage |
|---|---|
| Week 1 through Week 4 | 5 mg twice daily |
| Week 5 through Week 8 | If Hb is below normal range or patient has required a transfusion within the last 8 weeks:
|
| Week 9 through Week 12 | If Hb is below normal range or patient has required a transfusion within the last 8 weeks:
|
| Maintenance | If Hb decreases, consider up-titration to the maximum of 50 mg twice daily as per the above schedule. |
Missed Dose
If a dose of PYRUKYND is missed by 4 hours or less, administer the dose as soon as possible. If a dose of PYRUKYND is missed by more than 4 hours, do not administer a replacement dose, and wait until the next scheduled dose. Subsequently, return to the normal dosing schedule.
Interruption or Discontinuation
To reduce the risk of acute hemolysis, avoid abrupt interruption or abrupt discontinuation of PYRUKYND when possible [see Warnings and Precautions (5.1)]. Taper the dose to gradually discontinue the medication (see Table 2). Monitor patients for signs of acute hemolysis and worsening of anemia.
| Current Dose | Dose Taper Schedule | ||
|---|---|---|---|
| Day 1-7 | Day 8-14 | Day 15 | |
| Abbreviations: N/A = not applicable. | |||
| 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 |
Recommended Dosage for Hepatic Impairment
Avoid use of PYRUKYND in patients with moderate or severe hepatic impairment [see Use in Special Populations (8.6) and Clinical Pharmacology (12.3)].
Recommended Dosage for Drug Interactions
Strong CYP3A Inhibitors
Avoid co-administration of strong CYP3A inhibitors with PYRUKYND [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Moderate CYP3A Inhibitors
Monitor Hb and for increased risks of adverse reactions from PYRUKYND. When used with a moderate CYP3A inhibitor, do not titrate PYRUKYND beyond 20 mg twice daily [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Strong CYP3A Inducers
Avoid co-administration of strong CYP3A inducers with PYRUKYND [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Moderate CYP3A Inducers
Consider alternative therapies that are not moderate CYP3A inducers during treatment with PYRUKYND. If there are no alternative therapies, monitor Hb and titrate beyond the 50 mg twice daily dose, if necessary, but do not exceed a maximum recommended dose of 100 mg twice daily [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
Dose Modifications for Adverse Reactions and Hemoglobin Levels Above Normal
If a dose reduction is required because of an adverse reaction or tolerability, or for Hb above normal, 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 PYRUKYND, the dose taper schedule (Table 2) should be followed. In situations where the risk to the patient due to the adverse reaction or Hb above normal is greater than the risk of acute hemolysis due to sudden withdrawal of the drug, treatment may be stopped without taper and patients should be monitored for signs of acute hemolysis.
