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Sylvant in the multicentric Castleman’s disease: important safety information

Siltuximab ( Sylvant ) is an anti-interleukin-6 ( IL-6 ) chimeric monoclonal antibody that binds to human IL-6.1 IL-6 is a multifunctional cytokine produced by various cells such as T cells, B cells, monocytes, fibroblasts and endothelial cells. Dysregulated overproduction of IL-6 from activated B cells in affected lymph nodes has been implicated in the pathogenesis of, or mechanism causing, multicentric Castleman’s disease ( MCD ).

Multicentric Castleman’s disease is a rare blood disorder with high morbidity in which lymphocytes, a type of white blood cell, are over-produced and lead to enlargement of lymph nodes.
Multicentric Castleman’s disease can also affect lymphoid tissue of internal organs, causing the liver, spleen or other organs to enlarge.
Signs and symptoms are driven by dysregulated IL-6 production. Common symptoms include enlarged lymph nodes ( appearing as lumps under the skin ), fever, weakness, fatigue, night sweats, weight loss, loss of appetite, nausea, vomiting and nerve damage that leads to numbness and weakness.
Some symptoms can be life threatening. Infections, multisystem organ failure and malignancies including malignant lymphoma are common causes of death in patients with multicentric Castleman’s disease.

Unlike unicentric Castleman’s disease, which is localized and affects only a single area or group of lymph nodes, patients with multicentric Castleman’s disease have more than one group of lymph nodes in different anatomical areas that are affected.
Unicentric disease can be treated by surgically removing the diseased lymph node, while multicentric disease is usually much more difficult to treat.

Castleman’s disease is formally diagnosed through a lymph node biopsy. The number of people diagnosed with Castleman’s disease is unknown, but the disease is known to be rare.

Important safety information

a) Contraindications - Severe hypersensitivity reaction to Siltuximab or any of the excipients in Sylvant.

b) Concurrent active severe infections - Do not administer to patients with severe infections until the infection resolves. Monitor patients closely for infections. Institute prompt anti-infective therapy and do not administer further Sylvant until the infection resolves.

c) Vaccinations - Do not administer live vaccines to patients receiving Sylvant because interleukin-6 ( IL-6 ) inhibition may interfere with the normal immune response to new antigens.

d) Infusion related reactions and hypersensitivity - Stop the infusion if the patient develops signs of anaphylaxis. Discontinue further therapy. Stop the infusion if the patient develops mild to moderate infusion reactions. If the reaction resolves, the infusion may be restarted at a lower infusion rate. Consider medicating with antihistamines, Acetaminophen ( Paracetamol ), and corticosteroids. Discontinue Sylvant if the patient does not tolerate the infusion following these interventions.

e) Gastrointestinal perforation - Use with caution in patients who may be at increased risk for gastrointestinal perforation. Promptly evaluate patients presenting with symptoms that may be associated or suggestive of gastrointestinal perforation.

f) Adverse reactions - The most common adverse reactions ( greater than 10% compared to placebo ) in the clinical trial were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.

g) Drug interactions - Cytochrome P450 ( CYP450 ) substrates - Upon initiation or discontinuation of Sylvant, in patients being treated with CYP450 substrates with narrow therapeutic index, perform therapeutic monitoring of effect ( e.g., Warfarin [ Coumadin ] ) or drug concentration ( e.g. Cyclosporine or Theophylline ) as needed and adjust dose. Exercise caution when Sylvant is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable ( e.g., oral contraceptives, Lovastatin, Atorvastatin ).

Source: Janssen Biotech, 2014