Dosing
SYLVANT® (siltuximab) Dosing and Administration1
SYLVANT is administered by intravenous infusion once every 3 weeks until treatment failure. Preadministration tests are conducted before the treatment. See below or download the detailed Dosing and Administration Guide for specific information related to testing, infusion preparation, and more.
- Dosing
- Preadministration
- Preparation
- Administration
3 weeks
11 mg/kg administered over 1 hour by intravenous infusion, every 3 weeks until treatment failure
Preadministration
Laboratory Tests Ensure Effective Use of SYLVANT1
Hematology laboratory tests should be performed prior to each dose of SYLVANT therapy for the first 12 months and every 3 dosing cycles thereafter. If the treatment criteria in the table below are not met, consider delaying treatment until values improve. Do not reduce the dose.
It is not safe to administer SYLVANT to patients with severe infections.
| Laboratory parameter | Requirements before first SYLVANT administration | Re-treatment 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 |
- SYLVANT may increase hemoglobin levels in patients with MCD.
Administration
Preparing for an Infusion1
-
Strength 100-mg vial 400-mg vial Amount of Sterile Water for Injection, USP required for reconstitution 5.2 mL 20 mL Post-reconstitution concentration 20 mg/mL 20 mg/mL - Calculate the dose (mg) and total volume (mL) of reconstituted SYLVANT solution required and the number of vials needed
- Allow the vial(s) of SYLVANT to come to room temperature over approximately 30 minutes. SYLVANT should remain at room temperature for the duration of the preparation
- Aseptically reconstitute each SYLVANT vial as instructed in the table to the right
- Once reconstituted, and prior to further dilution, inspect the vials for particulates and discoloration. Do not use if particles or solution discoloration are present or if visibly opaque. The reconstituted product should be kept for no more than 2 hours prior to addition into the infusion bag
- Dilute the reconstituted SYLVANT solution dose in the infusion bag
- Administer SYLVANT over 1 hour by infusion
- DO NOT SHAKE or SWIRL VIGOROUSLY
- GENTLY swirl the reconstituted vials to aid the dissolution of the lyophilized powder
- Do not remove the contents until all of the solids have been
completely dissolved - The lyophilized powder should dissolve in less than 60 minutes
SYLVANT [package insert]. Hertfordshire, UK: EUSA Pharma UK Ltd; 2019.
Important Safety Information
Indications and Usage
SYLVANT® (siltuximab) 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.
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.
Contraindications
Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.
Warnings and Precautions
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 receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens.
Infusion Related Reactions and Hypersensitivity
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
Gastrointestinal (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.
Adverse Reactions
The most common adverse reactions (>10% compared to placebo) in the MCD clinical trial were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infections.
Drug Interactions
Cytochrome P450 Substrates
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).
Dosage 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 the Prescribing Information are not met, consider delaying treatment with SYLVANT. Do not reduce dose.
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.
Please see full Prescribing Information for additional important safety information.
Important Safety Information
Indications and Usage
SYLVANT® (siltuximab) 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.
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.
Contraindications
Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.
Warnings and Precautions
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 receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens.
Infusion Related Reactions and Hypersensitivity
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
Gastrointestinal (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.
Adverse Reactions
The most common adverse reactions (>10% compared to placebo) in the MCD clinical trial were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infections.
Drug Interactions
Cytochrome P450 Substrates
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).
Dosage 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 the Prescribing Information are not met, consider delaying treatment with SYLVANT. Do not reduce dose.
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.
Please see full Prescribing Information for additional important safety information.
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