Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Infusion related reactions
Infusion related reactions have been reported with imlifidase administration in clinical studies (seesection 4.8). If any serious allergic or anaphylactic reaction occurs, imlifidase therapy should be discontinued immediately and appropriate therapy initiated. Mild or moderate infusion-related reactions occurring during imlifidase treatment can be managed by temporarily interrupting the infusion, and/or by administration of medicinal products, such as antihistamines, antipyretics and corticosteroids. An interrupted infusion can be restarted when the symptoms have abated.
Infection and infection prophylaxis

For kidney transplantation, ongoing serious infections of any origin (bacterial, viral or fungal) are considered a contraindication, and chronic infections such as HBV or HIV have to be well controlled. The temporary reduction of
IgG by imlifidase must be taken into consideration. The most common infections in patients with hypogammaglobulinemia are respiratory tract infections. Therefore, in addition to the standard of care infection prophylaxis in kidney transplantation in general (against Pneumocystis carinii, cytomegalovirus and oral candida), all patients should also receive prophylacticoral antibiotics covering respiratory tract pathogens for 4 weeks. Should a patient for any reason not be transplanted after imlifidase treatment, prophylactic oral antibiotics covering respiratory tract pathogens should still be given for 4 weeks.


Use of imlifidase and T-cell depleting induction therapy with or without memory B-cell depleting therapies may increase the risk of reactivation of live-attenuated vaccines and/or latent tuberculosis.

Vaccinations

Due to the reduced IgG levels after treatment with imlifidase, there is a risk for a temporary reduction of vaccine protection for up to 4 weeks following imlifidase treatment.

Antibody-mediated rejection (AMR)

AMR may occur as a consequence of rebound of donor-specific antibodies (DSA). Patients with very high levels of DSA before transplantation are more likely to experience early AMR that requires intervention. Most patients in the clinical studies had rebound of DSA that peaked between 7 and
21 days after imlifidase treatment, and AMR occurred in approximately 30% of the patients. All patients with AMR in clinical studies were successfully managed with standard of care treatment. The re-appearance of DSAs and increased risk of AMR in highly sensitised patients require physician’s previous experience from managing sensitised patients, resources and preparedness to diagnose and treat acute AMRs according to standard clinical practice. Management of patients should include closemonitoring of anti-HLA (human leukocyte antigen) antibodies and serum or plasma creatinine as well as readiness to perform biopsies when AMR is suspected.

Patients with positive T-cell complement-dependent cytotoxicity (CDC) crossmatch test 
There is very limited experience in patients with a confirmed positive T-cell CDC-crossmatch test before imlifidase treatment (see section 5.1).

Immunogenicity

The potential influence of anti-imlifidase antibodies (anti-drug antibodies, ADA) on the efficacy and safety of a second imlifidase dose given within 24 hours of the first is expected to be negligible, since the production of ADA in response to the first dose has not yet started to develop.

Confirmation of crossmatch conversion

Each clinic should follow its standard protocol for confirmation of crossmatch conversion from positive to negative. If complement-dependent cytotoxicity crossmatch (CDCXM) is used, the following needs to be considered to avoid false positive results: IgM has to be inactivated to be able to specifically assess the cytotoxic capacity of IgG. The use of an anti-human globulin (AHG) step should be avoided. If used, it should be confirmed that the AHG is directed against the Fc-part and not against the Fab-part of the IgG. Use of AHG, directed against the Fab-part, will not allow correct readout of a CDCXM in an imlifidase-treated patient.
Antibody-based medicinal products

Imlifidase is a cysteine protease that specifically cleaves IgG. As a consequence, IgG-based medicinalproducts may be inactivated if given in connection with imlifidase. Antibody-based medicinal products cleaved by imlifidase include, but are not limited to basiliximab, rituximab, alemtuzumab, adalimumab, denosumab, belatacept, etanercept, rabbit anti-thymocyte globulin (rATG) and intravenous immunoglobulin (IVIg) (see section 4.5 for recommended time intervals between administration of imlifidase and antibody-based medicinal products).

IVIg may contain neutralising antibodies against imlifidase, which may inactivate imlifidase if IVIg is given before imlifidase (see section 4.5).

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
Not relevant.