Version July 2025
Note: Consider delaying first dose if ANC <1000/mm3, platelets <75,000/mm3, and hemoglobin ≥17 g/dL; subsequent doses may be delayed if ANC <1000/mm3, platelets <50,000/mm3, and hemoglobin ≥17 g/dL. Do not administer to patients with severe infections until infection resolves. Do not reduce dose.
Castleman disease, multicentric (in patients who are HIV negative and HHV-8 negative): IV: 11 mg/kg once every 3 weeks until treatment failure (Ref). For initial disease control, adjunctive corticosteroids may be also administered for 4 to 8 weeks, followed by a corticosteroid taper; patients who are more symptomatic may require higher initial doses of adjunctive corticosteroids and a more gradual taper (Ref).
Severe disease in critically ill patients (off-label dosing): IV: 11 mg/kg once weekly for one month (Ref), followed by 11 mg/kg once every 3 weeks until treatment failure. For initial disease control, also administer adjunctive high-dose corticosteroids, followed by a slow corticosteroid taper (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥15 mL/minute: No initial dosage adjustment is necessary.
CrCl <15 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
End-stage renal disease (ESRD): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Hepatic impairment prior to treatment initiation:
Mild to moderate impairment (Child-Turcotte-Pugh class A, B): No initial dosage adjustment is necessary.
Severe impairment (Child-Turcotte-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: The dosing in the FDA-approved prescribing information should be followed in all patients, regardless of obesity status. If a patient with a BMI ≥30 kg/m2 experiences high-grade toxicity from systemic anticancer therapy, the same dosage modification recommendations should be followed for all patients, regardless of obesity status (Ref).
Cytokine release syndrome: Permanently discontinue siltuximab.
Hematologic toxicity: ANC <1,000/mm3, platelets <50,000/mm3, and hemoglobin ≥17 g/dL: Consider delaying treatment with siltuximab until ANC ≥1,000/mm3, platelets ≥50,000/mm3, and hemoglobin <17 g/dL.
Infection, severe: Withhold siltuximab until infection resolves; initiate appropriate anti-infective therapy as clinically indicated.
Infusion reactions: Immediately interrupt siltuximab infusion for reaction of any severity. Manage symptoms as clinically appropriate.
Grade 1 or 2 (mild to moderate) infusion reactions: Once symptoms resolve, resume siltuximab infusion at a lower infusion rate. Consider antihistamines, acetaminophen, and corticosteroids. If patient does not tolerate infusion following intervention, permanently discontinue siltuximab.
Grade 3 (severe) infusion reactions: Permanently discontinue siltuximab.
Grade 4 (anaphylactic reaction or life-threatening) infusion reaction: Permanently discontinue siltuximab.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Edema (≤26%)
Dermatologic: Pruritus (28%), skin rash (28%)
Endocrine & metabolic: Weight gain (19%), hyperuricemia (11%)
Local: Localized edema (≤26%)
Respiratory: Upper respiratory tract infection (26%)
1% to 10%:
Cardiovascular: Hypotension (4%)
Central nervous system: Headache (8%)
Dermatologic: Eczema (4%), psoriasis (4%), skin hyperpigmentation (4%), xeroderma (4%)
Endocrine & metabolic: Hypertriglyceridemia (8%), hypercholesterolemia (4%)
Gastrointestinal: Constipation (8%)
Hematologic & oncologic: Thrombocytopenia (9%)
Hypersensitivity: Hypersensitivity reaction (≤6.3%)
Immunologic: Antibody development (2%, non-neutralizing)
Renal: Renal insufficiency (8%)
Respiratory: Lower respiratory tract infection (8%), oropharyngeal pain (8%)
Miscellaneous: Infusion related reaction (≤6.3%)
Frequency not defined:
Cardiovascular: Hypertension
Central nervous system: Dizziness
Gastrointestinal: Abdominal pain, diarrhea, gastroesophageal reflux disease, nausea, oral mucosa ulcer, vomiting
Genitourinary: Urinary tract infection
Hematologic & oncologic: Neutropenia
Respiratory: Nasopharyngitis
<1%: Anaphylaxis
Severe hypersensitivity to siltuximab or any component of the formulation.
Concerns related to adverse effects:
• Gastrointestinal perforation: Gastrointestinal perforation has been observed in clinical trials. Use with caution in patients at risk for perforation; promptly evaluate concerning symptoms.
• Hemoglobin levels: Siltuximab administration may result in elevated hemoglobin levels in patients with multicentric Castleman disease.
• Infection: Siltuximab may mask signs and symptoms of infection, including signs of acute inflammation (eg, fever, C-reactive protein elevation).
• Infusion-related/hypersensitivity reactions: Hypersensitivity, anaphylactic reaction, and drug hypersensitivity have been observed with siltuximab. Symptoms of infusion reactions include back pain, chest pain or discomfort, nausea and vomiting, flushing, erythema, and/or palpitations.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Vaccinations: Do not administer live vaccines to patients receiving siltuximab; interleukin 6 (IL-6) inhibition may interfere with immune response to vaccination.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Sylvant: 100 mg (1 ea); 400 mg (1 ea) [contains polysorbate 80]
No
Solution (reconstituted) (Sylvant Intravenous)
100 mg (per each): $1,909.56
400 mg (per each): $7,638.25
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Sylvant: 100 mg (1 ea); 400 mg (1 ea) [contains mouse (murine) and/or hamster protein, polysorbate 80]
Siltuximab is available through specialty pharmacies and various specialty institutions or accounts. Examples from the manufacturer may be found at https://sylvant.com/hcp/resources-for-idiopathic-multicentric-castleman-disease.
IV: Administer IV over 1 hour using administration sets lined with polyvinyl chloride (PVC), polyurethane (PU), or polyethylene (PE), which contain a 0.2-micron inline polyethersulfone (PES) filter. Do not infuse in the same line with other medications. Complete infusion within 4 hours of dilution of the reconstituted solution to the infusion container.
Administer in a setting equipped to provide resuscitation equipment; medications for the treatment of hypersensitivity reactions (eg, bronchodilators, epinephrine, antihistamines, corticosteroids) should be readily available.
Castleman disease: Treatment of multicentric Castleman disease (MCD) in patients who are HIV negative and human herpesvirus-8 (HHV-8) negative.
Limitations of use: Siltuximab has not been studied in patients with MCD who are HIV positive or HHV-8 positive because in a nonclinical study, siltuximab did not bind to virally produced interleukin 6 (IL-6).
Siltuximab may be confused with isatuximab, loncastuximab tesirine, margetuximab, rituximab, sarilumab, sutimlimab.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CycloSPORINE (Systemic): Interleukin-6 (IL-6) Inhibiting Therapies may decrease serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
HMG-CoA Reductase Inhibitors (Statins): Interleukin-6 (IL-6) Inhibiting Therapies may decrease serum concentration of HMG-CoA Reductase Inhibitors (Statins). Risk C: Monitor
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Theophylline: Interleukin-6 (IL-6) Inhibiting Therapies may decrease serum concentration of Theophylline. Risk C: Monitor
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Patients who could become pregnant should use effective contraception during treatment and for 3 months after the last dose of siltuximab.
Siltuximab is a humanized monoclonal antibody; monoclonal antibodies are expected to cross the placenta, generally increasing as pregnancy progresses. Infants born to pregnant patients treated with siltuximab may be at increased risk for infection.
It is not known if siltuximab is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 3 months following the last dose of siltuximab.
Monitor CBC with differential prior to each dose for the first 12 months and every 3 dosing cycles thereafter, or as clinically necessary. Monitor for anaphylaxis and signs/symptoms of infusion-related, allergic, or cytokine release reactions; monitor for infection and signs/symptoms of GI perforation.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Chimeric monoclonal antibody which binds with high affinity and specificity to IL-6; prevents IL-6 from binding to both soluble and membrane-bound IL-6 receptors. Overproduction of IL-6 may lead to systemic manifestations in multicentric Castleman disease (MCD) patients by inducing C-reactive protein (CRP) synthesis (Kurzrock 2013). Lowering serum IL-6 levels may improve systemic symptoms of Castleman disease.
Onset: Response is usually evident after 3 to 4 doses; lymphadenopathy resolves at a median of 5 months (van Rhee 2018)
Distribution: 4.5 L
Half-life elimination: ~21 days (range: 14.2 to 29.7 days)
