Siltuximab

Siltuximab binds human IL-6 and prevents the binding of IL-6 to both soluble and membrane-bound IL-6 receptors. IL-6 has been shown to be involved in diverse normal physiologic processes such as induction of immunoglobulin secretion.

• SYLVANT is indicated for the treatment of patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. SYLVANT is an interleukin-6 (IL-6) antagonist indicated for the treatment of patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.ICD-10: B20

• Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT [see Warnings and Precautions (5.3) ] . Hypersensitivity reactions, including anaphylactic reaction, hypersensitivity, and drug hypersensitivity have been reported in patients treated with siltuximab.contraindicated

For intravenous infusion only. Administer as an 11 mg/kg dose given over 1 hour by intravenous infusion every 3 weeks. ( 2 ) 2.1 Recommended Dosage Administer SYLVANT 11 mg/kg over 1 hour as an intravenous infusion every 3 weeks until treatment failure. Perform hematology laboratory tests prior to each dose of SYLVANT therapy for the first 12 months and every 3 dosing cycles thereafter. If treatment criteria outlined in Table 1 are not met, consider delaying treatment with SYLVANT. Do not reduce dose. Table 1: Treatment Criteria Laboratory parameter Requirements before first SYLVANT administration Retreatment criteria Absolute Neutrophil Count ≥1.0 × 10 9 /L ≥1.0 × 10 9 /L Platelet count ≥75 × 10 9 /L ≥50 × 10 9 /L Hemoglobin SYLVANT may increase hemoglobin levels in MCD patients <17 g/dL <17 g/dL Do not administer SYLVANT to patients with severe infections until the infection resolves. Discontinue SYLVANT in patients with severe infusion related reactions, anaphylaxis, severe allergic reactions, or cytokine release syndromes. Do not reinstitute treatment. 2.2 Instructions for Preparation and Administration Use aseptic technique for reconstitution and preparation of dosing solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit 1. Calculate the dose (mg), total volume (mL) of reconstituted SYLVANT solution required and the number of vials needed. A 21-gauge 1½ inch needle is recommended for preparation.

Concurrent Active Severe Infections: Do not administer SYLVANT to patients with severe infections, monitor for infections, institute prompt treatment, and interrupt SYLVANT until resolution of infection. ( 2 , 5.1 ) Vaccinations: Do not administer live vaccines because IL-6 inhibition may interfere with the normal immune response to new antigens. ( 5.2 ) Infusion Related Reactions: Administer SYLVANT in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation. ( 5.3 , 6.1 ) Gastrointestinal (GI) perforation: Promptly evaluate patients presenting with symptoms that may be associated or suggestive of GI perforation. ( 5.4 ) 5.1 Concurrent Active Severe Infections Do not administer SYLVANT 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 receiving SYLVANT closely for infections. Institute prompt anti-infective therapy and do not administer further SYLVANT until the infection resolves. 5.2 Vaccinations Do not administer live vaccines to patients or infants born to patients receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens [see Use in Specific Populations (8.1) ]. 5.3 Infusion Related Reactions and Hypersensitivity SYLVANT may cause infusion related reactions and anaphylaxis. Approximately 945 patients have been treated with SYLVANT in clinical trials.

The following clinically significant adverse reactions are also discussed in other sections of the labeling: Concurrent active severe infections [see Warnings and Precautions (5.1) ] Infusion-related reactions and hypersensitivity [see Warnings and Precautions (5.3) ] Gastrointestinal perforation [see Warnings and Precautions (5.4) ] The most common adverse reactions (>10% of patients) were rash, pruritus, upper respiratory tract infection, increased weight, and hyperuricemia. To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc., at 1-888-575-8344 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Study 1, in MCD, was an international, multicenter, randomized Phase 2 study of every 3 week infusions comparing SYLVANT and best supportive care (BSC) to placebo and BSC. There were 53 patients randomized to the SYLVANT arm at a dosage of 11 mg/kg and 26 patients randomized to the placebo arm. Of the 26 placebo-treated patients, 13 patients subsequently crossed-over to receive SYLVANT. The median age was 48 years (range 20 to 78), 66% male, 48% Asian, 39% White, 4% Black or African American, 7% other.

Pregnancy: May cause fetal harm ( 8.1 ) 8.1 Pregnancy Risk-Summary In an animal reproduction study, intravenous administration of a human antibody to IL-6 to pregnant monkeys from the onset of organogenesis through delivery caused functional impairment in pregnant animals and in the offspring. Siltuximab and the human antibody to IL-6 crossed the placenta in monkeys ( see Data ). The limited available information on SYLVANT use during pregnancy is not sufficient to inform a drug-associated risk of major birth defects or miscarriage. Infants born to pregnant women treated with SYLVANT may be at increased risk of infection (see Clinical Considerations ). Advise pregnant women of the potential risk to a fetus. The estimated background risk for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Clinical Considerations Fetal/Neonatal adverse reactions Monoclonal antibodies are transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Infants born to pregnant women treated with SYLVANT may be at increased risk of infection.

Metabolism

The pharmacokinetics of siltuximab were evaluated in patients with multicentric Castleman's disease and hematological and non-hematological malignancies. The serum siltuximab pharmacokinetics are adequately described by a linear two-compartment intravenous model with first-order elimination.

• Apr 23, 2014BLABLA125496Recordati Rare Diseases, Inc.

1. 1Off Label Use12821%
2. 2Drug Ineffective9416%
3. 3Cytokine Release Syndrome538.9%
4. 4Immune Effector Cell-associated Neurotoxicity Syndrome427.0%
5. 5Hypertension416.9%
6. 6Disease Progression366.0%
7. 7Cataract325.4%
8. 8Death325.4%
9. 9Drug Effective For Unapproved Indication325.4%
10. 10Hepatic Steatosis315.2%
11. 11Cushingoid305.0%
12. 12Osteopenia305.0%
13. 13Short Stature305.0%
14. 14Product Use In Unapproved Indication274.5%
15. 15Spinal Instability254.2%

The 10 most recently updated of 44 ClinicalTrials.gov registrations naming Siltuximab as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Clinical Trial of MK-1045 in People With B-cell Acute Lymphoblastic Leukemia (MK-1045-005)
  Recruiting · Phase 2 · Phase 3 · Interventional · 340 enrolled · Merck Sharp & Dohme LLC
  NCT07570173updated 2026-06-05
• Study to Evaluate the Role of Siltuximab in Treatment of Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) Related to CAR-T Cell Therapy
  Completed · Phase 2 · Interventional · 24 enrolled · University of Alabama at Birmingham
  NCT04975555updated 2026-06-03
• A Study of Melphalan With or Without Siltuximab in People With Multiple Myeloma Having an Autologous Stem Cell Transplant
  Recruiting · Phase 2 · Interventional · 215 enrolled · Memorial Sloan Kettering Cancer Center
  NCT06679829updated 2026-04-24
• Screening Trial for Pain Relief in Schwannomatosis (STARFISH)
  Recruiting · Phase 2 · Interventional · 40 enrolled · Massachusetts General Hospital
  NCT05684692updated 2026-04-23
• Siltuximab in Large Granular Lymphocytic Leukemia (LGLL)
  Terminated · Early phase 1 · Interventional · 6 enrolled · H. Lee Moffitt Cancer Center and Research Institute
  NCT05316116updated 2026-02-05
• Siltuximab for the Prevention of Severe Immune-Related Adverse Events During Immune Checkpoint Inhibitor Rechallenge in Patients With Advanced Cancer, CIRES Trial
  Recruiting · Phase 2 · Interventional · 40 enrolled · Yuanquan Yang
  NCT06470971updated 2026-01-20
• A Phase 1 Clinical Trial of Siltuximab for the Treatment of Antibody-Mediated Rejection After Lung Transplantation
  Recruiting · Phase 1 · Interventional · 30 enrolled · Washington University School of Medicine
  NCT06990711updated 2025-12-31
• Siltuximab to Decrease Symptom Burden After Autologous Stem Cell Transplantation for Patients With Multiple Myeloma and AL Amyloidosis
  Active not recruiting · Phase 2 · Interventional · 30 enrolled · Memorial Sloan Kettering Cancer Center
  NCT03315026updated 2025-11-04
• Siltuximab and Spartalizumab in Patients With Metastatic Pancreatic Cancer
  Completed · Phase 1 · Phase 2 · Interventional · 35 enrolled · Emory University
  NCT04191421updated 2025-08-22
• A Phase II Study of Siltuximab for CRS/ICANs After CAR-T in Multiple Myeloma
  Recruiting · Phase 2 · Interventional · 20 enrolled · Institute of Hematology & Blood Diseases Hospital, China
  NCT07106671updated 2025-08-06

Frequently asked questions

How does Siltuximab work?

Siltuximab binds human IL-6 and prevents the binding of IL-6 to both soluble and membrane-bound IL-6 receptors. IL-6 has been shown to be involved in diverse normal physiologic processes such as induction of immunoglobulin secretion.

What is Siltuximab used for?

According to FDA labeling, Siltuximab carries indications including: SYLVANT is indicated for the treatment of patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. SYLVANT is an interleukin-6 (IL-6) antagonist indicated for the treatment of patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Siltuximab?

Siltuximab is classified as Interleukin inhibitors, Interleukin-6 Antagonist, Interleukin-6 Antagonists, Decreased Immunologic Activity.

What are the brand names for Siltuximab?

Siltuximab is marketed under brand names including Sylvant.

What are the contraindications for Siltuximab?

Siltuximab labeling lists contraindications including: Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT [see Warnings and Precautions (5.3) ] . Hypersensitivity reactions, including anaphylactic reaction, hypersensitivity, and drug hypersensitivity have been reported in patients treated with siltuximab.. Always consult the full prescribing information and a clinician.