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Indications and Dosage
Intravenous
Multicentric Castleman’s disease Adult: In patients who are HIV-negative and human herpesvirus-8 (HHV-8) negative: 11 mg/kg given via infusion over 1 hour once every 3 weeks until treatment failure. Consider delaying doses if absolute neutrophil count (ANC) is <1,000 cells/mm3, platelet count <75,000 cells/mm3 before the 1st dose or <50,000 cells/mm3 before any subsequent doses, and Hb ≥17 g/dL. Dose reduction is not recommended.
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Reconstitution
Reconstitute vial labelled as 100 mg and 400 mg with 5.2 mL and 20 mL sterile water for inj respectively, to make a final concentration of 20 mg/mL. Gently swirl to mix; do not shake. To prepare the solution for infusion, further dilute the reconstituted solution with 250 mL of dextrose 5% in water (D5W) within 2 hours. Slowly add the reconstituted solution to the 250 mL D5W infusion bag and gently invert to mix.
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Contraindications
Severe infections (until resolved). Concomitant use with live vaccines.
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Special Precautions
Patient with chronic infections, history of recurrent infection, or underlying conditions predisposing to infection; at risk of gastrointestinal perforation (e.g. diverticulitis, ulcers). Not indicated for use in HIV-positive and HHV-8 positive patients. Pregnancy and lactation.
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Adverse Reactions
Significant: Hypersensitivity, anaphylactic reactions, cytokine-release syndrome, infusion-related reaction, mask signs and symptoms of infection and acute inflammation (e.g. C-reactive protein elevation, fever), serious infection (e.g. pneumonia, sepsis), gastrointestinal perforation, increased risk of malignancy, transient or intermittent increase in hepatic transaminases or other LFTs, including bilirubin; elevated lipid, cholesterol, and Hb levels.
Blood and lymphatic system disorders: Neutropenia, thrombocytopenia. Gastrointestinal disorders: Nausea, abdominal pain, vomiting, constipation, diarrhoea, GERD, mouth ulceration. General disorders and administration site conditions: General or localised oedema. Immune system disorders: Antibody development. Investigations: Increased weight. Metabolism and nutrition disorders: Hypertriglyceridaemia, hypercholesterolaemia, hyperuricaemia. Musculoskeletal and connective tissue disorders: Pain in extremity, arthralgia. Nervous system disorders: Headache, dizziness. Renal and urinary disorders: Renal impairment, UTI. Respiratory, thoracic and mediastinal disorders: Upper and lower respiratory tract infection, oropharyngeal pain, nasopharyngitis. Skin and subcutaneous tissue disorders: Rash, pruritus, psoriasis, eczema, skin hyperpigmentation, xeroderma. Vascular disorders: Hypotension, hypertension. |
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IV/Parenteral: C
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Patient Counseling Information
Women of childbearing potential must use proven birth control methods during therapy and for 3 months after stopping the treatment.
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Monitoring Parameters
Obtain CBC with differential prior to each dose for the 1st 12 months and every 3 dosing cycles thereafter, or as necessary. Monitor for signs or symptoms of anaphylaxis, infusion-related or cytokine release reactions, gastrointestinal perforation, and infection.
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Drug Interactions
May increase the metabolism of CYP450 substrates (e.g. warfarin, theophylline, ciclosporin). May decrease the effects of CYP3A4 substrates (e.g. oral contraceptives, atorvastatin, lovastatin).
Potentially Fatal: May enhance the adverse effects of live vaccines. |
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Action
Description: Siltuximab is a recombinant chimeric human-murine monoclonal antibody that binds with high affinity and specificity to interleukin-6 (IL-6). It prevents the binding of human IL-6 to both soluble and membrane-bound IL-6 receptors. The overproduction of IL-6 may result in systemic manifestations of multicentric Castleman’s disease (MCD) by induction of C-reactive protein synthesis. Lowering the serum IL-6 levels may improve these systemic symptoms.
Pharmacokinetics: Distribution: Volume of distribution: 4.5 L. Excretion: Elimination half-life: Approx 21 days (range: 14.2-29.7 days). |
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Storage
Intact vial: Store between 2-8°C. Do not freeze. Protect from light. Reconstituted and diluted solutions are stable for 8 hours between 15-25°C.
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MIMS Class
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ATC Classification
L04AC11 - siltuximab ; Belongs to the class of interleukin inhibitors. Used as immunosuppressants.
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References
Anon. Siltuximab. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/10/2022. Anon. Siltuximab. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/10/2022. Buckingham R (ed). Siltuximab. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/10/2022. Joint Formulary Committee. Siltuximab. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/10/2022. Link Pharmaceuticals Ltd. Sylvant 100 mg and 400 mg Powder for Infusion Concentrate data sheet 4 February 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 06/10/2022. Sylvant 100 mg and 400 mg Powder for Concentrate for Solution for Infusion (Link Healthcare Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/10/2022. Sylvant 100 mg Powder for Concentrate for Solution for Infusion (EUSA Pharma [UK] Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 06/10/2022. Sylvant Injection, Powder for Solution (EUSA Pharma [UK] Ltd). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/10/2022.
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