Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: EUSA Pharma (Netherlands) B.V., Johannes Vermeerplein 11, 1071 DV, Amsterdam, Netherlands
SYLVANT is indicated for the treatment of adult patients with multicentric Castleman’s disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.
This medicinal product should be administered by qualified healthcare professionals and under appropriate medical supervision.
The recommended dose is 11 mg/kg siltuximab given over 1 hour as an intravenous infusion administered every 3 weeks until treatment failure.
Haematology laboratory tests should be performed prior to each dose of SYLVANT therapy for the first 12 months and every third dosing cycle thereafter. Before administering the infusion, the prescriber should consider delaying treatment, if the treatment criteria outlined in Table 1 are not met. Dose reduction is not recommended.
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 |
| Haemoglobina | <170 g/L (10.6 mmol/L) | <170 g/L (10.6 mmol/L) |
a SYLVANT may increase haemoglobin levels in MCD patients
The SYLVANT therapy should be withheld if the patient has a severe infection or any severe non-haematological toxicity and can be restarted at the same dose after recovery.
If the patient develops a severe infusion related reaction, anaphylaxis, severe allergic reaction, or cytokine release syndrome related to the infusion, further administration of SYLVANT should be discontinued. Discontinuing the medicinal product should be considered if there are more than 2 dose delays due to toxicities related to the treatment during the first 48 weeks.
No major age-related differences in pharmacokinetics (PK) or in safety profile were observed in clinical studies. No dose adjustment is required (see section 5.2).
No formal studies have been conducted to investigate the PK of siltuximab in patients with renal or hepatic impairment (see section 4.4).
The safety and efficacy of siltuximab in children aged 17 years and younger have not been established.
No data are available.
Siltuximab must be administered as an intravenous infusion. For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.
No case of overdose has been reported in clinical trials. In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse effects and appropriate symptomatic treatment should be instituted immediately.
Unopened vial: 3 years.
After reconstitution and dilution: Chemical and physical in-use stability has been demonstrated for up to 8 hours at room temperature (see section 6.6).
From a microbiological point of view, unless the method of opening/reconstitution/dilution precludes the risk of microbial contamination, the product should be used immediately.
If not used immediately, in-use storage times and conditions are the responsibility of the user.
Store in a refrigerator (2°C-8°C). Do not freeze. Store in the original package in order to protect from light.
For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.
SYLVANT 100 mg powder for concentrate for solution for infusion: 8 mL Type 1 glass vial with an elastomeric closure and an aluminium seal with a flip-off button containing 100 mg of siltuximab. Pack size of 1 vial.
SYLVANT 400 mg powder for concentrate for solution for infusion: 30 mL Type 1 glass vial with an elastomeric closure and an aluminium seal with a flip-off button containing 400 mg of siltuximab. Pack size of 1 vial.
This medicinal product is for single use only.
Use aseptic technique.
Calculate the dose, total volume of reconstituted SYLVANT solution required and the number of vials needed. The recommended needle for preparation is 21-gauge 1½ inch (38 mm). Infusion bags (250 mL) must contain dextrose 5% and must be made of polyvinyl chloride (PVC), or polyolefin (PO), or polypropylene (PP), or polyethylene (PE). Alternatively PE bottles may be used.
Allow vial(s) of SYLVANT to come to room temperature (15°C to 25°C) over approximately 30 minutes. SYLVANT should remain at room temperature for the duration of the preparation.
Each 100 mg vial should be reconstituted with 5.2 mL of single-use water for injections to yield a 20 mg/mL solution.
Each 400 mg vial should be reconstituted with 20 mL of single-use water for injections to yield a 20 mg/mL solution.
Gently swirl (DO NOT SHAKE OR VORTEX OR SWIRL VIGOROUSLY) the reconstituted vials to aid the dissolution of the powder. Do not remove contents until all of the powder has been completely dissolved. The powder should dissolve in less than 60 minutes. Inspect the vials for particulate matter and discolouration prior to dose preparation. Do not use if visibly opaque or if foreign particles and/or solution discolouration are present.
Dilute the total volume of the reconstituted solution dose to 250 mL with sterile dextrose 5%, by withdrawing a volume equal to the volume of reconstituted SYLVANT from the dextrose 5%, 250 mL bag. Slowly add the total volume of reconstituted SYLVANT solution to the 250 mL infusion bag. Gently mix.
The reconstituted solution should be kept for no more than 2 hours prior to addition into the intravenous bag. The infusion should be completed within 6 hours of the addition of the reconstituted solution to the infusion bag. Administer the diluted solution over a period of 1 hour using administration sets lined with PVC, or polyurethane (PU), or PE, containing a 0.2-micron inline polyethersulfone (PES) filter. SYLVANT does not contain preservatives; therefore do not store any unused portion of the infusion solution for re-use.
No physical biochemical compatibility studies have been conducted to evaluate the co-administration of SYLVANT with other medicinal products. Do not infuse SYLVANT concomitantly in the same intravenous line with other agents.
Any unused product or waste material should be disposed of in accordance with local requirements.
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