Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Infections
Ilaris 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 Ilaris. Physicians should exercise caution when administering Ilaris 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 SJIA
Ilaris should not be initiated or continued in patients during an active infection requiring medical intervention.
Treatment of gouty arthritis
Ilaris should not be administered during an active infection.
Concomitant use of Ilaris 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 Ilaris treatment. The causal relationship of Ilaris to these events cannot be excluded.
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 Ilaris without clinical evidence of a latent or active tuberculosis infection.
It is unknown whether the use of interleukin-1 (IL-1) inhibitors such as Ilaris 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 Ilaris. All patients should be instructed to seek medical advice if signs or symptoms suggestive of tuberculosis (e.g.
ILA API MAR17 CL V6                                         REF EMA SmPC APP 2.3.17 persistent cough, weight loss, subfebrile temperature) appear during Ilaris 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 Ilaris. Treatment with Ilaris 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 Ilaris.
The risk for the development of malignancies with anti-interleukin (IL)-1 therapy is unknown.

Hypersensitivity reactions
Hypersensitivity reactions with Ilaris therapy have been reported. The majority of these events were mild in severity. During clinical development of Ilaris in over 2,600 patients, no anaphylactoid or anaphylactic reactions 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 Ilaris. Therefore, live vaccines should not be given concurrently with Ilaris unless the benefits clearly outweigh the risks (see section 4.5).
Prior to initiation of Ilaris 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 SJIA patients
Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in patients with rheumatic conditions, in particular SJIA. 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 SJIA, as these are known triggers for MAS. Based on clinical trial experience, Ilaris does not appear to increase the incidence of MAS in SJIA patients, but no definitive conclusion can be made.

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