Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Infections
Canakinumab is associated with an increased incidence of serious infections. Therefore patients should be monitored carefully for signs and symptoms of infections during and after treatment with canakinumab.
Physicians should exercise caution when administering canakinumab to patients with infections, a history of recurring infections or underlying conditions which may predispose them to infections.

Treatment of CAPS, TRAPS, HIDS/MKD, FMF and Still’s disease (SJIA and AOSD) Canakinumab should not be initiated or continued in patients during an active infection requiring medical intervention.

Treatment of gouty arthritis
Canakinumab should not be administered during an active infection.

Concomitant use of canakinumab with tumour necrosis factor (TNF) inhibitors is not recommended because this may increase the risk of serious infections (see section 4.5).
Isolated cases of unusual or opportunistic infections (including aspergillosis, atypical mycobacterial infections, herpes zoster) have been reported during canakinumab treatment. The causal relationship of canakinumab to these events cannot be excluded.

Tuberculosis screening

ILR API Dec21 V4                           Based on EU SmPC 28.09.2021 In approximately 12% of CAPS patients tested with a PPD (purified protein derivative) skin test in clinical trials, follow-up testing yielded a positive test result while treated with canakinumab without clinical evidence of a latent or active tuberculosis infection.

It is unknown whether the use of interleukin-1 (IL-1) inhibitors such as canakinumab increases the risk of reactivation of tuberculosis. Before initiation of therapy, all patients must be evaluated for both active and latent tuberculosis infection. Particularly in adult patients, this evaluation should include a detailed medical history. Appropriate screening tests (e.g., tuberculin skin test, interferon gamma release assay or chest X-ray) should be performed in all patients (local recommendations may apply). Patients must be monitored closely for signs and symptoms of tuberculosis during and after treatment with canakinumab .
All patients should be instructed to seek medical advice if signs or symptoms suggestive of tuberculosis (e.g. persistent cough, weight loss, subfebrile temperature) appear during canakinumab therapy. In the event of conversion from a negative to a positive PPD test, especially in high-risk patients, alternative means of screening for a tuberculosis infection should be considered.

Neutropenia and leukopenia
Neutropenia (absolute neutrophil count [ANC] < 1.5 x 109/l) and leukopenia have been observed with medicinal products that inhibit IL-1, including canakinumab. Treatment with canakinumab should not be initiated in patients with neutropenia or leukopenia. It is recommended that white blood cell (WBC) counts including neutrophil counts be assessed prior to initiating treatment and again after 1 to 2 months.
For chronic or repeated therapies, it is also recommended to assess WBC counts periodically during treatment. If a patient becomes neutropenic or leukopenic, the WBC counts should be monitored closely and treatment discontinuation should be considered.

Malignancies
Malignancy events have been reported in patients treated with canakinumab.
The risk for the development of malignancies with anti-interleukin (IL)-1 therapy is unknown.

Hypersensitivity reactions
Hypersensitivity reactions with canakinumab therapy have been reported. The majority of these events were mild in severity. During clinical development of canakinumab in over 2,600 patients, no anaphylactoid or anaphylactic reactions attributable to treatment with canakinumab were reported.
However, the risk of severe hypersensitivity reactions, which is not uncommon for injectable proteins, cannot be excluded (see section 4.3).

Hepatic function
Transient and asymptomatic cases of elevations of serum transaminases or bilirubin have been reported in clinical trials (see section 4.8).

Vaccinations
No data are available on the risk of secondary transmission of infection by live (attenuated) vaccines in patients receiving canakinumab . Therefore, live vaccines should not be given concurrently with canakinumab unless the benefits clearly outweigh the risks (see section 4.5).

Prior to initiation of canakinumab therapy it is recommended that adult and paediatric patients receive all vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza vaccine (see section 4.5).

Mutation in NLRP3 gene in CAPS patients
Clinical experience in CAPS patients without a confirmed mutation in the NLRP3 gene is limited.

Macrophage activation syndrome in patients with Still’s disease (SJIA and AOSD) Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in patients with rheumatic conditions, in particular Still’s disease . If MAS occurs, or is suspected, evaluation and treatment should be started as early as possible. Physicians should be attentive to symptoms of infection or worsening of Still’s disease, as these are known triggers for MAS. Based on 
ILR API Dec21 V4                          Based on EU SmPC 28.09.2021 clinical trial experience, canakinumab does not appear to increase the incidence of MAS in Still’s disease patients, but no definitive conclusion can be made.


Drug reaction with eosinophilia and systemic symptoms (DRESS)
Drug reaction with eosinophilia and systemic symptoms (DRESS) has rarely been reported in patients treated with Ilaris, predominantly in patients with systemic juvenile idiopathic arthritis (sJIA). Patients with DRESS may require hospitalization, as this condition may be fatal. If signs and symptoms of DRESS are present and an alternative aetiology cannot be established, Ilaris should not be re-administered and a different treatment considered.

Effects on Driving

4.7     Effects on ability to drive and use machines

Ilaris has minor influence on the ability to drive and use machines. Treatment with Ilaris may result in dizziness/vertigo or asthenia (see section 4.8). Patients who experience such symptoms during Ilaris treatment should wait for this to resolve completely before driving or operating machines.