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Siltuximab: Drug information

Siltuximab: Drug information
(For additional information see "Siltuximab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
Siltuximab: Coronavirus disease 2019 (COVID-19) October 2020

Most recent update(s): The National Institute of Health’s COVID-19 guidelines recommend against the use of anti-IL-6 monoclonal antibodies, such as siltuximab, for the treatment of COVID-19, except in a clinical trial.

As part of our response to the evolving COVID-19 pandemic, published literature and guidelines from major health organizations are continuously monitored for potential content updates. At this time, only investigational medications with data determined to be of relatively high quality and/or consistently showing positive clinical outcomes to support dosing recommendations will be included in the Lexicomp monograph, outside of this Special Alert field.

Further information may be found at:

Infectious Diseases Society of America: https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/

ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/results?cond=covid19&term=siltuximab&cntry=&state=&city=&dist=&Search=Searchi

Brand Names: US
  • Sylvant
Brand Names: Canada
  • Sylvant
Pharmacologic Category
  • Antineoplastic Agent, Monoclonal Antibody;
  • Interleukin-6 Inhibitor
Dosing: Adult

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 reduce dose.

Castleman disease, multicentric

Castleman disease, multicentric (in patients who are HIV negative and HHV-8 negative): IV: 11 mg/kg once every 3 weeks until treatment failure (van Rhee 2014; manufacturer's labeling). 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 (van Rhee 2018).

Severe disease in critically ill patients (off-label dosing): IV: 11 mg/kg once weekly for one month, 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 (van Rhee 2018).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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).

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment (Child Pugh class A or B): No initial dosage adjustment is necessary.

Severe impairment (Child Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Adjustment for Toxicity: Adult

Hematologic toxicity: ANC <1000/mm3, platelets <50,000/mm3, and hemoglobin ≥17 g/dL: Consider delaying treatment until ANC ≥1000/mm3, platelets ≥50,000/mm3, and hemoglobin <17 g/dL

Anaphylaxis, cytokine release syndromes, and/or severe infusion-related or allergic reactions: Discontinue permanently.

Infection, severe: Withhold treatment until infection resolves.

Dosage Forms: US

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]

Generic Equivalent Available: US

No

Dosage Forms: Canada

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]

Administration: Adult

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.

Use: Labeled Indications

Castleman disease: Treatment of multicentric Castleman disease (MCD) in patients who are human immunodeficiency virus (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 IL-6

Medication Safety Issues
Sound-alike/look-alike issues:

Siltuximab may be confused with isatuximab, loncastuximab tesirine, rituximab, sarilumab.

Adverse Reactions

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

Contraindications

Severe hypersensitivity to siltuximab or any component of the formulation

Warnings/Precautions

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; monitor blood counts prior to each dose for the first 12 months and every 3 dosing cycles thereafter, or as clinically necessary. May require therapy interruption.

• Infection: Siltuximab may mask signs and symptoms of infection, including signs of acute inflammation (eg, fever, C-reactive protein elevation). Do not administer to patients with severe infections (until infection resolves); monitor closely for infections and initiate appropriate anti-infective therapy if needed. If infection develops, withhold therapy until resolved.

• Infusion-related/hypersensitivity reactions: Hypersensitivity, anaphylactic reaction, and drug hypersensitivity have been observed with siltuximab. Discontinue infusion immediately (and permanently) if signs of anaphylaxis occur; do not reinitiate therapy. Discontinue in patients with severe infusion reaction, severe allergic reactions, or cytokine release syndromes. If a mild to moderate infusion reaction develops, temporarily discontinue the infusion; if the reaction resolves, may reinitiate at a lower infusion rate. Consider premedication with acetaminophen, antihistamines, and corticosteroids. If infusion-related reactions recur despite appropriate premedication and infusion rate reduction, discontinue therapy. Administer in a setting equipped to provide resuscitation equipment; medications for the treatment of hypersensitivity reactions (eg, bronchodilators, epinephrine, antihistamines, and corticosteroids) should be readily available.

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; IL-6 inhibition may interfere with immune response to vaccination.

Metabolism/Transport Effects

None known.

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA vaccine at least 28 days after the primary vaccine dose. Patients should also receive 2 booster doses of mRNA vaccine - one 2 months after the 2nd (additional) dose and another 4 months after the first booster dose. Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 based on the brand of mRNA vaccine received. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CYP2C9 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Interleukin-6 (IL-6) Inhibiting Therapies may decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect 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

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If post-exposure rabies vaccination is required during immunosuppressant therapy, administer a 5th dose of vaccine and check for rabies antibodies. Risk D: Consider therapy modification

Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Females of reproductive potential should use effective contraception during treatment and for 3 months after the last dose of siltuximab.

Pregnancy Considerations

Siltuximab is a humanized monoclonal antibody; monoclonal antibodies are expected to cross the placenta, generally increasing as pregnancy progresses. Infants born to pregnant females treated with siltuximab may be at increased risk for infection.

Breastfeeding Considerations

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.

Monitoring Parameters

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.

Mechanism of Action

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.

Pharmacokinetics

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)

Pricing: US

Solution (reconstituted) (Sylvant Intravenous)

100 mg (per each): $1,523.27

400 mg (per each): $6,093.07

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.

Brand Names: International
  • Sylvant (AU, BE, BR, CH, CY, CZ, DE, DK, EE, ES, FR, GB, HK, HR, HU, IE, IL, KR, LT, LU, MT, NL, NO, NZ, PL, RO, SE, SG, SI, SK)


For country abbreviations used in Lexicomp (show table)
  1. Alade SL, Brown RE, Paquet A Jr. Polysorbate 80 and E-Ferol toxicity. Pediatrics. 1986;77(4):593-597. [PubMed 3960626]
  2. Centers for Disease Control (CDC). Unusual syndrome with fatalities among premature infants: association with a new intravenous vitamin E product. MMWR Morb Mortal Wkly Rep. 1984;33(14):198-199. [PubMed 6423951]
  3. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  4. Isaksson M, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002;47(5):312-313. doi:10.1034/j.1600-0536.2002.4705104.x. [PubMed 12534540]
  5. Kurzrock R, Voorhees PM, Casper C, et al. A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Clin Cancer Res. 2013;19(13):3659-3670. [PubMed 23659971]
  6. Lucente P, Iorizzo M, Pazzaglia M. Contact sensitivity to Tween 80 in a child. Contact Dermatitis. 2000;43(3):172. [PubMed 10985636]
  7. National Institutes of Health (NIH). COVID-19 Treatment Guidelines Panel. Coronavirus disease 2019 (COVID-19) treatment guidelines. https://www.covid19treatmentguidelines.nih.gov/. Updated September 1, 2020. Accessed September 3, 2020.
  8. Shelley WB, Talanin N, Shelley ED. Polysorbate 80 hypersensitivity. Lancet. 1995;345(8960):1312-1313. doi: 10.1016/s0140-6736(95)90963-x. [PubMed 7746084]
  9. Sylvant (siltuximab) [prescribing information]. Hemel Hempstead, Hertfordshire, United Kingdom: EUSA Pharma (UK); December 2019.
  10. van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124. doi: 10.1182/blood-2018-07-862334. [PubMed 30181172]
  11. van Rhee F, Wong RS, Munshi N, et al. Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial [published correction appears in: Lancet Oncol. 2014;15(10):417.]. Lancet Oncol. 2014;15(9):966-974. doi: 10.1016/S1470-2045(14)70319-5. [PubMed 25042199]
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