CONTRAINDICATIONS – Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT®. Hypersensitivity reactions, including anaphylactic reaction, hypersensitivity, and drug hypersensitivity have been reported in patients treated with siltuximab.
Concurrent Active Severe Infections – Do not administer to patients with severe infections until the infection resolves. SYLVANT® may mask signs and symptoms of acute inflammation including suppression of fever and of acute phase reactants such as C-reactive protein (CRP). Monitor patients closely for infections. Institute prompt anti-infective therapy and do not administer further SYLVANT® until the infection resolves.
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.
Infusion Related Reactions and Hypersensitivity – SYLVANT® may cause infusion related reactions and anaphylaxis. In clinical trials, one out of approximately 945 patients experienced an anaphylactic reaction. Infusion related reactions were reported in 5.1% of 254 patients. Two (0.8%) were Grade 3 or higher, and 1 (0.4%) was serious; none were fatal. Symptoms of infusion reactions consisted of back pain, chest pain or discomfort, nausea and vomiting, flushing, erythema, and palpitations.
In long-term treatment of MCD patients with siltuximab at the recommended dosage of 11 mg/kg every 3 weeks, infusion related reactions or hypersensitivity reactions occurred at a frequency of 6.3% (1.3% for severe reactions).
Stop the infusion if the patient develops signs of anaphylaxis. Discontinue further therapy with SYLVANT®.
Stop the infusion if the patient develops a mild to moderate infusion reaction. If the reaction resolves, the infusion may be restarted at a lower infusion rate. Consider medication with antihistamines, acetaminophen, and corticosteroids. Discontinue SYLVANT® if the patient does not tolerate the infusion following these interventions.
Administer SYLVANT® in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation.
Gastrointestinal (GI) Perforation – 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.
Adverse Reactions – The most common adverse reactions (>10% compared to placebo) in the MCD clinical trial were rash (28%), pruritus (28%), upper respiratory tract infection (26%), increased weight (19%), and hyperuricemia (11%).
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) 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).
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