HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use SYLVANT™ safely and effectively. See full prescribing information for SYLVANT.
SYLVANT (siltuximab) for Injection, for Intravenous Infusion
Initial U.S. Approval: [2014]
3 月20 日，CHMP 基于质量、安全性和有效性数据，建议批准Sylvant(siltuximab)100 mg 和400 mg 配置溶液的粉末上市，治疗多中心性Castleman’s 病(MCD)。2007年11 月30 日siltuximab 被授予孤儿药称号。Siltuximab为一种人小鼠嵌合的单抗，与人白介素6(IL-6)高亲和度特异性结合。批准的适应证为“ 治疗人免疫缺陷病毒(HIV)和人疱疹病毒-8型(HHV-8)阴性的MCD”。
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use SYLVANT™ safely and effectively. See full prescribing information for SYLVANT.
SYLVANT (siltuximab) for Injection, for Intravenous Infusion
Initial U.S. Approval: [2014]
INDICATIONS AND USAGE
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. (1)
Limitation 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.
DOSAGE AND ADMINISTRATION
For intravenous infusion only.
Administer as an 11 mg/kg dose given over 1 hour by intravenous infusion every 3 weeks. (2)
DOSAGE FORMS AND STRENGTHS
100 mg of lyophilized powder in a single-use vial. (3)
400 mg of lyophilized powder in a single-use vial. (3)
CONTRAINDICATIONS
Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT. (4)
WARNINGS AND PRECAUTIONS
Concurrent Active Severe Infections
Do not administer SYLVANT to patients with severe infections until the infection resolves. (2)
Monitor patients receiving SYLVANT closely for infections. Institute prompt anti-infective therapy and do not administer SYLVANT until the infection resolves. (2)
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. (6.1)
Gastrointestinal (GI) perforation: Use with caution in patients who may be at increased risk. Promptly eva luate patients presenting with symptoms that may be associated or suggestive of GI perforation. (5.4)
ADVERSE REACTIONS
The most common adverse reactions (>10% compared to placebo) during treatment with SYLVANT in the MCD clinical trial were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection.
To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 6/2014
3 月20 日，CHMP 基于质量、安全性和有效性数据，建议批准Sylvant(siltuximab)100 mg 和400 mg 配置溶液的粉末上市，治疗多中心性Castleman’s 病(MCD)。2007年11 月30 日siltuximab 被授予孤儿药称号。Siltuximab为一种人小鼠嵌合的单抗，与人白介素6(IL-6)高亲和度特异性结合。批准的适应证为“ 治疗人免疫缺陷病毒(HIV)和人疱疹病毒-8型(HHV-8)阴性的MCD”。
Back to Highlights and Tabs
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Dosage
2.2 Instructions for Preparation and Administration
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Concurrent Active Severe Infections
5.2 Vaccinations
5.3 Infusion Related Reactions and Hypersensitivity
5.4 Gastrointestinal Perforation
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
7 DRUG INTERACTIONS
7.1 Cytochrome P450 Substrates
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Patients with Renal Impairment
8.7 Patients with Hepatic Impairment
10 OVERDOSAGE
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage and Stability
17 PATIENT COUNSELING INFORMATION
*
Sections or subsections omitted from the full prescribing information are not listed.
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
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.
Limitation 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.
2 DOSAGE AND ADMINISTRATION
2.1 Dosage
SYLVANT 11 mg/kg is given over 1 hour as an intravenous infusion administered 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 × 109/L |
≥1.0 × 109/L |
|
Platelet count |
≥75 × 109/L |
≥50 × 109/L |
|
Hemoglobin* |
<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.
1. Calculate the dose (mg), total volume (mL) of reconstituted SYLVANT solution required and the number of vials needed. A 21-gauge 1-½ inch needle is recommended for preparation. Infusion bags (250 mL) must contain Dextrose 5% in Water and must be made of Polyvinyl chloride (PVC) with Di-{2-ethylhexyl}phthalate (DEHP), or Polyolefin (PO).
2. 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.
3. Aseptically reconstitute each SYLVANT vial as instructed in Table 2.
Table 2: Reconstitution Instructions
|
Strength |
Amount of Sterile Water for Injection, USP required for reconstitution |
Post-reconstitution concentration |
|
100 mg vial |
5.2 mL |
20 mg/mL |
|
400 mg vial |
20 mL |
20 mg/mL |
Gently swirl the reconstituted vials to aid the dissolution of the lyophilized powder. DO NOT SHAKE or SWIRL VIGOROUSLY. Do not remove the contents until all of the solids have been completely dissolved. The lyophilized powder should dissolve in less than 60 minutes.
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 two hours prior to addition into the infusion bag.
4. Dilute the reconstituted SYLVANT solution dose to 250 mL with sterile Dextrose 5% in Water by withdrawing a volume equal to the total calculated volume of reconstituted SYLVANT from the Dextrose 5% in Water, 250 mL bag. Slowly add the total calculated volume (mL) of reconstituted SYLVANT solution to the Dextrose 5% in Water infusion bag. Gently invert the bag to mix the solution.
5. Administer the diluted SYLVANT solution in 5% Dextrose in Water 250 mL by intravenous infusion over a period of 1 hour using administration sets lined with polyvinyl chloride (PVC) or polyurethane (PU), containing a 0.2-micron inline polyethersulfone (PES) filter. The infusion should be completed within 4 hours of the dilution of the reconstituted solution to the infusion bag.
6. Do not infuse SYLVANT concomitantly in the same intravenous line with other agents.
7. Do not store any unused portion of the reconstituted product or of the infusion solution. Waste material should be disposed of in accordance with local requirements.
3 DOSAGE FORMS AND STRENGTHS
SYLVANT (siltuximab) for Injection is available as:
100 mg of lyophilized powder in a single-use vial for intravenous infusion.
400 mg of lyophilized powder in a single-use vial for intravenous infusion.
4 CONTRAINDICATIONS
Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT.
5 WARNINGS AND PRECAUTIONS
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 receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens.
5.3 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 medication with antihistamines, acetaminophen, and corticosteroids. Discontinue SYLVANT if the patient does not tolerate the infusion following these interventions [see Adverse Reactions (6)].
Administer SYLVANT in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation.
5.4 Gastrointestinal 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 eva luate patients presenting with symptoms that may be associated or suggestive of GI perforation.
6 ADVERSE REACTIONS
The following adverse reactions are also discussed in other sections of the labeling:
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 tr
