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. 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.
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).
8). 4 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.
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. 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.
). 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. 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.
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