Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use

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

Concurrent active serious infections
Infections, including localised infections, should be treated prior to administration of SYLVANT.
Serious infections, including pneumonia and sepsis, were observed during clinical studies (see section 4.8).

Hypoglobulinaemia was observed in 4 to 11.3% of patients in the clinical study.
Decreases in total IgG, IgA, or IgM levels below normal were observed in the range of 4 to 11% patients in the MCD trial (Study 1).


All clinical studies with SYLVANT excluded patients with clinically significant infections, including those known to be hepatitis B surface antigen positive. Two cases of reactivated hepatitis B have been reported when SYLVANT was administered concomitantly with high dose dexamethasone, and bortezomib, melphalan and prednisone in multiple myeloma patients.

SYLVANT may mask signs and symptoms of acute inflammation including suppression of fever and of acute-phase reactants, such as C-reactive protein (CRP). Therefore, prescribers should diligently monitor patients receiving treatment in order to detect serious infections.

Vaccinations
Live, attentuated vaccines should not be given concurrently or within 4 weeks before initiating SYLVANT as clinical safety has not been established.

Lipid parameters
Elevations in triglycerides and cholesterol (lipid parameters) were observed in patients treated with SYLVANT (see section 4.8). Patients should be managed according to current clinical guidelines for management of hyperlipidaemia.

Infusion related reactions and hypersensitivity
During intravenous infusion of SYLVANT, mild to moderate infusion reactions may improve following slowing of or stopping the infusion. Upon resolution of the reaction, reinitiating the infusion at a lower infusion rate and therapeutic administration of antihistamines, acetaminophen, and corticosteroids may be considered. For patients who do not tolerate the infusion following these interventions, SYLVANT should be discontinued. During or following infusion, treatment should be discontinued in patients who have severe infusion related hypersensitivity reactions (e.g., anaphylaxis). The management of severe infusion reactions should be dictated by the signs and symptoms of the reaction. Appropriate personnel and medicinal product should be available to treat anaphylaxis if it occurs (see section 4.8).

Malignancy
Immunomodulatory medicinal products may increase the risk of malignancy. On the basis of limited experience with siltuximab the present data do not suggest any increased risk of malignancy.

Gastrointestinal perforation
Gastrointestinal (GI) perforation has been reported in siltuximab clinical trials although not in MCD trials. Use with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with symptoms that may be associated with or suggestive of GI perforation.

Hepatic impairment
Following treatment with SYLVANT in clinical trials, transient or intermittent mild-to-moderate elevation of hepatic transaminase levels or other liver function tests such as bilirubin have been reported. SYLVANT-treated patients with known hepatic impairment as well as patients with elevated transaminase or bilirubin levels should be monitored.

Effects on Driving

4.7   Effects on ability to drive and use machines

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