ASPAVELI Solution for infusion Ref.[49950] Active ingredients: Pegcetacoplan

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.

Switches from complement inhibitors other than eculizumab have not been studied. Discontinuing other complement inhibitors before reaching steady-state of pegcetacoplan should be done with caution (see section 5.2).

Dose adjustment

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 patient has a lactate dehydrogenase (LDH) level greater than 2 x upper limit of normal (ULN). In the event of a dose increase, LDH should be monitored twice weekly for at least 4 weeks (see section 4.4).

Missed dose

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

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, thighs, hips, or upper arms. Infusion sites should be at least 7.5 cm apart from each other. The infusion sites should be rotated between administrations. 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.

No case of overdose has been reported to date. In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted.

2 years.

Store in a refrigerator (2°C–8°C).

Store in the original carton to protect from light.

A Type I glass vial with a stopper (chlorobutyl), and a seal (aluminium) with a flip-off cap (polypropylene) containing 54 mg/mL of sterile solution.

Each single pack contains 1 vial.

Multipack containing 8 (8 packs of 1) vials.

Not all pack sizes may be marketed.

ASPAVELI comes as a ready-to-use solution in single-use vials. Because the solution contains no preservative, this medicinal product should be infused immediately after preparing the syringe.

ASPAVELI is a clear, colourless to slightly yellowish aqueous solution. Do not use if the liquid looks cloudy, contains particles, or is dark yellow.

Always bring the vial to the room temperature for approximately 30 minutes before use.

Remove the protective flip cap from the vial to expose the central portion of the gray rubber stopper of the vial. Clean the stopper with a new alcohol wipe and allow the stopper to dry. Do not use if the protective flip cap is missing or damaged.

Option 1: If using a needleless transfer device (such as a vial adapter), follow the instructions provided by the device manufacturer.

Option 2: If transfer is done using a transfer needle and a syringe, follow the instructions below:

• Attach a sterile transfer needle to a sterile syringe.
• Pull back the plunger to fill the syringe with air, which should be about 20 mL.
• Make sure the vial is in upright position. Do not turn the vial upside down.
• Push the air-filled syringe with transfer needle attached through the centre of the vial stopper.
• The tip of the transfer needle should not be in the solution to avoid creating bubbles.
• Gently push the air from the syringe into the vial. This will inject the air from the syringe into the vial.
• Invert the vial.
• With the transfer needle tip in the solution, slowly pull the plunger to fill the syringe with all the liquid.
• Remove the filled syringe and the transfer needle from the vial.
• Do not recap the transfer needle. Unscrew the needle and throw it away in the sharps container.

Follow the device manufacturer’s instructions to prepare the infusion pump and tubing.

Potential areas for infusion include the abdomen, thighs, hips, or upper arms. Rotate infusion sites from one infusion to the next. If there are multiple infusion sites, they should be at least 7.5 cm apart.

The typical infusion time is approximately 30 minutes (if using two sites) or approximately 60 minutes (if using one site).

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