Sylvant Siltuximab for Injection

1. Indications and Usage
Multicentric Castleman’s Disease (MCD):
Treatment of adult patients with human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative multicentric Castleman’s disease.
2. Dosage and Administration
Route of Administration:
For Intravenous (IV) Infusion ONLY.
Recommended Dosage:
Dose: 11 mg/kg administered every 3 weeks.
Duration: Administered until disease progression (defined as worsening of symptoms, radiologic progression, or worsening performance status) or unacceptable toxicity.
Infusion Rate: Administer the first infusion over 1 hour. If the first infusion is tolerated, subsequent infusions may be administered over 1 hour.
Preparation:
Reconstitute with Sterile Water for Injection and dilute with 5% Dextrose Injection.
3. Mechanism of Action
IL-6 Antagonist:
Siltuximab is a chimeric monoclonal antibody that binds with high specificity to human interleukin-6 (IL-6).
Blocking Signaling:
By binding to IL-6, siltuximab blocks the interaction of IL-6 with both soluble and membrane-bound IL-6 receptors.
Pathogenesis:
In MCD patients, overproduction of IL-6 is associated with systemic symptoms and lymphoproliferation. Blocking IL-6 signaling reduces the release of proinflammatory cytokines, thereby inhibiting the inflammatory cascade and lymph node growth.
4. Safety and Warnings
Serious Infections (Boxed Warning):
Siltuximab may increase the risk of infections. Patients should be evaluated for active infections prior to initiation. Do not administer during active infection.
Hypersensitivity and Infusion-Related Reactions:
Serious hypersensitivity reactions (e.g., anaphylaxis) and infusion-related reactions have been reported.
Gastrointestinal Perforation:
Cases of GI perforation have been reported in MCD patients treated with siltuximab. Monitor patients for signs and symptoms of GI perforation.
Masking of Inflammation:
Suppression of acute phase reactants (e.g., C-reactive protein, CRP) may mask the signs and symptoms of infection.
Vaccinations:
Avoid live vaccines during treatment.
5.Adverse Reactions
Most Common:
Rash, pruritus, upper respiratory tract infections, diarrhea, pyrexia, cough, and fatigue.
6.Drug Interactions
CYP450 Substrates:
Chronic inflammation can suppress CYP450 enzyme activity. Blocking IL-6 signaling with siltuximab may normalize CYP450 activity.
Caution: Monitor dosage of CYP1A2, CYP2C9, or CYP3A4 substrates (e.g., theophylline, warfarin, cyclosporine) when starting siltuximab, as their metabolism may increase.
7.Pharmaceutical Information
Chemical Composition:
Active Ingredient: Siltuximab.
Available Strength: 100 mg and 400 mg lyophilized powder for IV infusion in a single-dose vial.
Appearance: White to off-white powder.
Storage: Store at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.