PYRUKYND Film-coated tablet Ref.[50547] Active ingredients: Mitapivat

Posology

The recommended starting dose is 5 mg taken orally twice daily.

To gradually increase haemoglobin (Hb) levels and maximise the effect, Pyrukynd 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 Pyrukynd is intended to be long-term. Pyrukynd 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:

Interruption or discontinuation

To minimise the risk of acute haemolysis, abrupt interruption or discontinuation of Pyrukynd 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 (see sections 4.4 and 4.8).

Table 2. Dose taper schedule:

N/A: not applicable.

Missed dose

If a dose of Pyrukynd 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.

Dose adjustments due to adverse events

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.

Special populations

Elderly

There are limited data available in elderly patients. No dose modifications are recommended in elderly patients (see sections 5.1 and 5.2).

Hepatic impairment

There are no data available in patients with hepatic impairment. No dose recommendations can be made.

Renal impairment

There are limited data available in patients with mild or moderate renal impairment. No dose modifications are recommended in patients with mild or moderate renal impairment (see section 5.2).

There are no data available in patients with severe renal impairment. No dose recommendations can be made.

Paediatric population

The safety and efficacy of Pyrukynd in children and adolescents less than 18 years old have not been established. No data are available. Non-clinical studies in juvenile animals have been conducted (see section 5.3).

Method of administration

For oral use.

Pyrukynd may be taken with or without food. The tablets should be swallowed whole. The tablets should not be split, crushed, chewed or dissolved because there are no data currently available to support other methods of administration.

In clinical studies in patients with PK deficiency, doses of mitapivat were assessed up to 300 mg twice daily. Healthy volunteers received up to 2 500 mg as a single dose and 700 mg twice daily for 14 days. One patient in a clinical study took 150 mg twice daily, a dose greater than the recommended dose in that study (50 mg twice daily) and did not experience any associated adverse events.

Patients who received higher than the recommended maximum dose of 50 mg twice daily in clinical studies reported adverse events consistent with the safety profile of mitapivat in all patients.

In case of overdose, patients should be treated symptomatically and provided with appropriate supportive measures as needed.

2 years.

Store below 25°C.

Mitapivat tablets are supplied in PVC/PCTFE/Al blister wallets in cartons.

Dose titration and maintenance packs

Pyrukynd 5 mg film-coated tablets:

Carton containing 56 film-coated tablets in 4 blister wallets, each containing 14 film-coated tablets.

Pyrukynd 20 mg film-coated tablets:

Carton containing 56 film-coated tablets in 4 blister wallets, each containing 14 film-coated tablets.

Pyrukynd 50 mg film-coated tablets:

Carton containing 56 film-coated tablets in 4 blister wallets, each containing 14 film-coated tablets.

Dose taper packs

Pyrukynd 5 mg film-coated tablets:

Carton containing 7 film-coated tablets in a blister wallet.

Pyrukynd 20 mg film-coated tablets + Pyrukynd 5 mg film-coated tablets:

Each carton of 14 film-coated tablets contains:

7 film-coated tablets of Pyrukynd 20 mg
7 film-coated tablets of Pyrukynd 5 mg

Pyrukynd 50 mg film-coated tablets + Pyrukynd 20 mg film-coated tablets:

Each carton of 14 film-coated tablets contains:

7 film-coated tablets of Pyrukynd 50 mg
7 film-coated tablets of Pyrukynd 20 mg

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.