Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Serious infections caused by encapsulated bacteria
The use of pegcetacoplan may predispose individuals to serious infections caused by encapsulated bacteria including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. To reduce the risk of infection, all patients must be vaccinated against these bacteria according to applicable local guidelines at least 2 weeks prior to receiving ASPAVELI, unless the risk of delaying therapy outweighs the risk of developing an infection.

Patients with known history of vaccination
Before receiving treatment with ASPAVELI, in patients with a known history of vaccination, it should be ensured that patients have received vaccines against encapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitidis types A, C, W, Y, and B, and Haemophilus influenzae Type B within 2 years prior to starting ASPAVELI.

Patients without known history of vaccination
For patients without known history of vaccination, the required vaccines should be administered at least 2 weeks prior to receiving the first dose of ASPAVELI. If immediate therapy is indicated, the required vaccines should be administered as soon as possible and the patient treated with appropriate antibiotics until 2 weeks after vaccination.

Monitoring patients for serious infections
Vaccination may not be sufficient to prevent serious infection. Consideration should be given to official guidance on the appropriate use of antibacterial agents. All patients should be monitored for early signs of infections caused by encapsulated bacteria including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, evaluated immediately if infection is suspected, and treated with appropriate antibiotics if necessary. Patients should be informed of these signs and symptoms, and steps taken to seek medical care immediately. Physicians must discuss the benefits and risks of ASPAVELI therapy with patients.

Hypersensitivity
Hypersensitivity reactions have been reported. If a severe hypersensitivity reaction (including anaphylaxis) occurs, infusion with ASPAVELI must be discontinued immediately, and appropriate treatment instituted.


Injection site reactions
Injection site reactions have been reported with the use of subcutaneous ASPAVELI (see section 4.8).
Patients should be trained appropriately in proper injection technique.

PNH laboratory monitoring
Patients with PNH receiving ASPAVELI should be monitored regularly for signs and symptoms of haemolysis, including measuring LDH levels, and may require dose adjustment within the recommended dosing schedule (see section 4.2).

Effects on laboratory tests
There may be interference between silica reagents in coagulation panels and pegcetacoplan that results in artificially prolonged activated partial thromboplastin time (aPTT); therefore, the use of silica reagents in coagulation panels should be avoided.

Treatment discontinuation for PNH
If patients with PNH discontinue treatment with ASPAVELI, they should be closely monitored for signs and symptoms of serious intravascular haemolysis. Serious intravascular haemolysis is identified by elevated LDH levels along with sudden decrease in PNH clone size or haemoglobin, or reappearance of symptoms such as fatigue, haemoglobinuria, abdominal pain, dyspnoea, major adverse vascular event (including thrombosis), dysphagia, or erectile dysfunction. If discontinuation of this medicinal product is necessary, alternate therapy should be considered. If serious haemolysis occurs after discontinuation, consider the following procedures/treatments: blood transfusion (packed RBCs), exchange transfusion, anticoagulation, and corticosteroids. Patients should be closely monitored for at least 8 weeks from the last dose, representing more than 5 half-lives of this medicinal product, to allow for medicinal product washout (see section 5.2) to detect serious haemolysis and other reactions. In addition, slow weaning should be considered.

Contraception in women of childbearing potential
It is recommended that women of childbearing potential use effective contraception methods to prevent pregnancy during treatment with pegcetacoplan and for at least 8 weeks after the last dose of pegcetacoplan (see section 4.6).

Polyethylene glycol (PEG) accumulation
ASPAVELI is a PEGylated medicinal product. The potential long-term effects of PEG accumulation in the kidneys, the choroid plexus of the brain, and other organs are unknown (see section 5.3).
Regular laboratory testing of renal function is recommended.

Excipients with known effect
Sorbitol content
ASPAVELI 1,080 mg contains 820 mg sorbitol in each vial.
Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product.

Sodium content
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say, essentially ‘sodium-free’.

Effects on Driving

4.7   Effects on ability to drive and use machines

ASPAVELI has no or negligible influence on the ability to drive and use machines.