Dosage & Administration

Administer SYLVANT® (siltuximab) intravenously
once every 3 weeks1

Preadministration
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 are not met, consider delaying treatment with SYLVANT. Do not reduce dose.1

Laboratory tests for effective use of SYLVANT1

Laboratory parameter
Requirements before first Retreatment criteria SYLVANT administration
Retreatment criteria
Absolute neutrophil count
≥1.0 x 109/L
≥1.0 x 109/L
Platelet count
≥75 x 109/L
≥50 x 109/L
Hemoglobina
<17 g/dL
<17 g/dL
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11 mg/kg administered by intravenous infusion until
treatment failure.1

dSYLVANT may increase hemoglobin levels in patients with multicentric 
Castleman disease.

Dosing

  • Do not administer SYLVANT to patients with severe infections until the infection resolves1
  • Discontinue SYLVANT in patients with severe infusion-related reactions, anaphylaxis, severe allergic reactions, or cytokine release syndromes. Do not reinstitute treatment1

Dosing Calculator

Accurate dosing is important for the optimal therapeutic benefits of SYLVANT. This user-friendly interface helps facilitate convenient and reliable calculations. Prior to infusion, enter the patient’s weight into the calculator tool to determine the correct dosage of SYLVANT. SYLVANT uses weight-based dosing (11 mg/kg).

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Perform hematology laboratory tests prior to each dose of SYLVANT therapy for the first 12 months and every 3 dosing cycles thereafter. See full Prescribing Information for treatment criteria.

Dosing & Administration Guide

Download this detailed Guide for specific information related to tests, infusion preparation, and more.

SYLVANT should be administered until treatment failure1

In the SYLVANT Phase 2 trial, a durable response was defined as tumor and symptomatic response that persisted
for a minimum of 18 weeks without treatment failure.1

The CDCN established assessment criteria for evaluating response to treatment,
taking into account all features of iMCD. These include:

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Objective biochemical markers of inflammatory response
and organ function (hemoglobin, CRP, albumin, eGFR)2
Response Evaluation: Monthly

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Lymph node size2
Response Evaluation: First recommended at 6 weeks and 
at 3-month intervals thereafter until maximum regression

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Clinical symptoms (fatigue, anorexia, fever, weight change)
as assessed by the clinician2
Response Evaluation: Monthly

Complete response requires normalization of biochemical markers, lymph node response by CT scan, and improvements in clinical symptoms2

Infusion-related reaction and hypersensitivity

  • If your patient has a mild to moderate infusion reaction or an allergic reaction while receiving SYLVANT, you must stop the infusion and treat their reaction. If the reaction resolves, then treatment with SYLVANT can be restarted at a lower infusion rate1
  • If your patient has a severe infusion or allergic reaction, you must stop treatment with SYLVANT completely1

For more information, see “International, Evidence-Based Consensus Treatment Guidelines for iMCD.”2

CDCN, Castleman Disease Collaborative Network; CRP, C-reactive protein; CT, computed tomography; eGFR, estimated glomerular filtration rate.

DID YOU KNOW?

In patients treated with anti–IL-6 treatments, lymph node response may take several months, with a median time to lymph node response of 5 months.2

Order SYLVANT

Order SYLVANT and access helpful patient resources and tools.

References: 1. SYLVANT [package insert]. Hertfordshire, UK: EUSA Pharma (UK) Ltd; 2019. 2. 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.

INDICATIONS AND USAGE

SYLVANT® (siltuximab) 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.

Limitations of Use
SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL-6 in a nonclinical study.

IMPORTANT SAFETY INFORMATION

SYLVANT is contraindicated in patients experiencing a 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 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.

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.

Infusion Related Reactions and Hypersensitivity: SYLVANT may cause infusion-related reactions and anaphylaxis. Stop the infusion of SYLVANT 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 SYLVANT infusion may be restarted at a lower infusion rate. Consider medicating 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: GI perforation has been reported in clinical trials although not in MCD trials. Use with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with symptoms that may be associated or suggestive of GI perforation.

The most common adverse reactions (>10% compared to placebo) during treatment with SYLVANT in the MCD clinical trial 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.

Drug Interactions with Cytochrome P450 (CYP450) Substrates: Inhibition of IL-6 signaling in patients treated with SYLVANT may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment with SYLVANT.

Upon initiation or discontinuation of SYLVANT, in patients being treated with CYP450 substrates with a narrow therapeutic index, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) as needed and adjust dose. The effect of SYLVANT on CYP450 enzyme activity can persist for several weeks after stopping therapy. 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).

Pregnancy and Lactation: SYLVANT may cause embryo-fetal harm when administered to pregnant women. Advise female patients of reproductive potential to use effective contraception during treatment with SYLVANT and for 3 months after the last dose. Advise patients not to breastfeed during treatment with SYLVANT and for 3 months after the final dose.

Pediatric Use: The safety and efficacy of SYLVANT have not been established in pediatric patients.

Dosing and Administration: 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 of the Prescribing Information are not met, consider delaying treatment with SYLVANT. Do not reduce dose.

SYLVANT® (siltuximab) for injection, for intravenous use, is available as 100 mg or 400 mg of lyophilized powder in a single-dose vial.

Please see the accompanying full Prescribing Information.

INDICATIONS AND USAGE

SYLVANT® (siltuximab) 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.

Limitations of Use

SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL-6 in a nonclinical study.

IMPORTANT SAFETY INFORMATION

SYLVANT is contraindicated in patients experiencing a 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.