Dosing and uses of Sylvant (siltuximab)
Adult dosage forms and strengths
lyophilized powder for reconstitution
- 100mg/vial
- 400mg/vial
Castleman Disease
Indicated for multicentric Castleman disease in patients who are negative for HIV and human herpesvirus-8
11 mg/kg IV q3weeks; infuse over 1 hr
Continue until treatment failure
Dosage modifications
Renal impairment
- CrCl ≥15 mL/min: No initial dosage adjustment required
- End-stage renal disease: No information
Hepatic impairment
- Mild-to-moderate (Child-Pugh A and B): No initial dosage adjustment required
- Severe (Child-Pugh C): No information
Dosing Considerations
Do not administer with severe infection until resolved
Discontinue with severe infusion-related reactions, anaphylaxis, severe allergic reactions, or cytokine release syndromes; do not reinstitute treatment
Hematology lab tests
- Perform hematology tests before each dose for first 12 months and every 3 dosing cycles thereafter
- If following criteria not met, consider delaying treatment (do NOT reduce dose):
- If following criteria not met, consider delaying treatment (do NOT reduce dose)
- ANC: ≥1 x 10^9/L
- Platelets: ≥75 x 10^9/L (before 1st dose); ≥50 x 10^9/L (retreatment criteria)
- Hgb: <17 g/dL
Pediatric dosage forms and strengths
Safety and efficacy not established
Sylvant (siltuximab) adverse (side) effects
>10%
Pruritus (28%)
Rash (28%)
Edema (16-26%)
Upper respiratory tract infection (26%)
Increased weight (19%)
Abdominal pain/distension (12%)
Hyperuricemia (11%)
1-10%
Thrombocytopenia (9%)
Lower respiratory tract infection (8%)
Constipation (8%)
Oropharyngeal pain (8%)
Renal impairment (8%)
Headache (8%)
Hypertriglyceridemia (8%)
Hypotension (4-6%)
Hypercholesterolemia (4%)
Skin hyperpigmentation (4%)
Eczema (4%)
Psoriasis (4%)
Dry skin (4%)
Decreased appetite (4%)
Dehydration (4%)
Warnings
Contraindications
Severe hypersensitivity
Cautions
Do not administer to patients with severe infections until the infection resolves; may mask signs and symptoms of acute inflammation, including suppression of fever and of acute phase reactants such as C-reactive protein
Monitor closely for infections; institute prompt, anti-infective therapy and do not administer further therapy with siltuximab until the infection resolves
Do not administer with live vaccines; may interfere with normal immune response
Stop infusion if signs of anaphylaxis occur; if mild-to-moderate reaction, may restart at lower infusion rate; consider premedicating with antihistamines, acetaminophen, and corticosteroids; discontinue if infusion not tolerated after these interventions
Advise women to avoid pregnancy; women of childbearing potential should use contraception during and for 3 months after treatment
Gastrointestinal perforation reported
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if distributed in human breast milk; because many drugs and immunoglobulins are excreted in human milk, a decision should be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of the drug to the mother
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Sylvant (siltuximab)
Mechanism of action
Anti-interleukin-6 (IL-6) monoclonal antibody
Binds human IL-6 and prevents the binding of IL-6 to both soluble and membrane-bound IL-6 receptors; overproduction of IL-6 has been linked to systemic manifestations of multicentric Castleman disease
Absorption
Peak plasma time: Occurs at end of IV infusion
Peak plasma concentration: 332 mcg/mL
Predose trough level: 84 mcg/mL
Distribution
Vd: 4.5 L (70 kg male)
Elimination
Half-life: 20.6 days
Clearance: 0.23 L/day
Administration
IV Preparation
Use aseptic technique
Calculate the dose and total volume of reconstituted solution required and the number of vials needed
Allow the vial(s) to come to room temperature over ~30 minutes
Siltuximab should remain at room temperature for the duration of the preparation
Reconstitute vials with sterile water for injection; 100-mg vial with 5.2 mL and 400-mg vial with 20 mL
Reconstituted concentration is 20 mg/mL
Gently swirl vials to aid dissolution of lyophilized powder; do NOT shake or swirl vigorously
Do not withdraw contents until all solids are completely dissolved (should dissolve in <60 minutes)
Within 2 hr of reconstitution, further dilute in D5W (PVC with DEHP, or polyolefin)
Withdraw volume from 250-mL bag of D5W that is equal to total calculated volume of reconstituted siltuximab, then slowly add calculated volume of reconstituted siltuximab; gently invert to mix solution
IV Administration
Administer in a setting that has resuscitation equipment, medication, and personnel trained to provide resuscitation
Administer IV over 1 hr using administration sets lined with PVC with DEHP or polyurethane containing a 0.2 micron inline polyethersulfone filter
Complete infusion within 4 hr of dilution of the reconstituted solution to the infusion bag
Do not infuse concomitantly in the same IV line with other agents
Do not store any unused portion of the reconstituted product or of the infusion solution
Storage
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF)
- Protect from light
- Contains no preservatives
