Posology : מינונים

4.2    Posology and method of administration

Therapy should be initiated under the supervision of a healthcare professional experienced in the management of patients with haematological disorders. Self-administration and home infusion should be considered for patients who have tolerated treatment well in experienced treatment centres. The decision of a possibility of self-administration and home infusions should be made after evaluation and recommendation from the treating physician.

Posology
Pegcetacoplan can be given by a healthcare professional, or administered by the patient or caregiver following proper instruction.


Pegcetacoplan is administered twice weekly as a 1,080 mg subcutaneous infusion with a commercially available syringe system infusion pump that can deliver doses up to 20 mL. The twice weekly dose should be administered on Day 1 and Day 4 of each treatment week.

PNH is a chronic disease and treatment with ASPAVELI is recommended to continue for the patient’s lifetime, unless the discontinuation of this medicinal product is clinically indicated (see section 4.4).

Patients switching to ASPAVELI from a C5 inhibitor
For the first 4 weeks, pegcetacoplan is administered as twice weekly subcutaneous doses of 1,080 mg in addition to the patient’s current dose of C5 inhibitor treatment to minimise the risk of haemolysis with abrupt treatment discontinuation. After 4 weeks, the patient should discontinue C5 inhibitor before continuing on monotherapy with ASPAVELI.

Dose adjustment for ASPAVELI
The dosing regimen may be changed to 1,080 mg every third day (e.g., Day 1, Day 4, Day 7, Day 10, Day 13, and so forth) if a subject has a lactate dehydrogenase (LDH) level greater than 2 x upper limit of normal. In the event of a dose increase, LDH should be monitored twice weekly for at least 4 weeks (see section 4.4).

Missed dose of ASPAVELI
If a dose of pegcetacoplan is missed, it should be administered as soon as possible, then the regular schedule should be resumed.

Special populations

Elderly (>65 years old)
Although there were no apparent age-related differences observed in clinical studies, the number of patients aged 65 and over is not sufficient to determine whether they respond differently from younger patients. There is no evidence indicating any special precautions are required for treating an elderly population.

Renal impairment
Severe renal impairment (creatinine clearance <30 mL/min) had no effect on the pharmacokinetics (PK) of pegcetacoplan; therefore, pegcetacoplan dose adjustment in patients with renal impairment is not necessary. There are no data available for the use of pegcetacoplan in patients with end-stage renal disease (ESRD) requiring haemodialysis (see section 5.2).

Hepatic impairment
The safety and efficacy of pegcetacoplan have not been studied in patients with hepatic impairment; however, no dose adjustment is recommended, as hepatic impairment is not expected to impact clearance of pegcetacoplan.

Paediatric population
The safety and efficacy of ASPAVELI in children with PNH aged 0 to <18 years have not yet been established. No data are available.
This medicinal product should not be used in children <12 years of age, as non-clinical safety data are not available for this age group.

Method of administration

ASPAVELI should only be administered via subcutaneous administration using a commercially available syringe system infusion pump. This medicinal product can be self-administered. When self-administration is initiated, the patient will be instructed by a qualified healthcare professional in infusion techniques, the use of a syringe system infusion pump, the keeping of a treatment record, the recognition of possible adverse reactions, and measures to be taken in case these occur.


ASPAVELI should be infused in the abdomen, thigh, or upper arms. Infusion sites should be at least 7.5 cm apart from each other. The infusion sites should be rotated between administration. Infusion into areas where the skin is tender, bruised, red, or hard should be avoided. Infusion into tattoos, scars, or stretch marks should be avoided. The typical infusion time is approximately 30 minutes (if using two sites) or approximately 60 minutes (if using one site). The infusion should be started promptly after drawing this medicinal product into the syringe. Administration should be completed within 2 hours after preparing the syringe. For instructions on the preparation and infusion of the medicinal product, see section 6.6.