Siltuximab

Siltuximab is used to treat multicentric Castleman disease in patients who are negative for HIV and human herpesvirus-8.

Siltuximab is available under the following different brand names: Sylvant

Dosages of Siltuximab:

Dosage Forms and Strengths

Lyophilized Powder for Reconstitution

• 100 mg/vial
• 400 mg/vial

Dosage Considerations – Should be Given as Follows:

Castleman Disease

• Indicated for multicentric Castleman disease in patients who are negative for HIV and human herpesvirus-8
• 11 mg/kg intravenously (IV) every 3 weeks; infuse over 1 hour
• Continue until treatment failure

Dosage Modifications

Renal impairment

• CrCl 15 mL/minute or greater: 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 is required
• Severe (Child-Pugh C): No information

Dosage Considerations

• Do not administer with severe infection until resolved
• Discontinue severe infusion-related reactions, anaphylaxis, severe allergic reactions, or cytokine release syndromes; do not reinstitute treatment
• Safety and efficacy not established in pediatric patients

Hematology lab tests

• Perform hematology tests before each dose for the first 12 months and every 3 dosing cycles thereafter
• If the following criteria are not met, consider delaying treatment (do NOT reduce dose):
• If the following criteria are not met, consider delaying treatment (do NOT reduce dose)
  • ANC: 1 x 10^9/L or greater
  • Platelets: 75 x 10^9/L (before 1st dose) or greater; 50 x 10^9/L (retreatment criteria) or greater
  • Hgb: less than17 g/dL

Common side effects of Siltuximab include:

• Itching
• Rash
• Fluid retention (edema)
• Upper respiratory tract infection
• Weight gain
• Abdominal pain/distension
• Hyperuricemia

Less common side effects of siltuximab include:

• Low blood platelets (thrombocytopenia)
• Lower respiratory tract infection
• Constipation
• Mouth and throat pain
• Renal impairment
• Headache
• High triglycerides (hypertriglyceridemia)
• Low blood pressure (hypotension)
• High cholesterol (hypercholesterolemia)
• Skin hyperpigmentation
• Eczema
• Psoriasis
• Dry skin
• Decreased appetite
• Dehydration

Postmarketing side effects of siltuximab reported include:

• Infections and infestations: Runny or stuffy noses, urinary tract infection (UTI)
• Blood and lymphatic system disorders: low white blood cell counts (neutropenia)
• Nervous system disorders: Dizziness
• Vascular disorders: High blood pressure (hypertension)
• Gastrointestinal disorders: Nausea, abdominal pain, vomiting, diarrhea, gastroesophageal reflux disease (GERD), mouth ulceration, gastrointestinal perforation

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

Siltuximab has no listed severe interactions with other drugs.

Serious interactions of siltuximab include:

• baricitinib
• palifermin

Siltuximab has moderate interactions with at least 28 different drugs.

Siltuximab has no listed mild interactions with other drugs.

Warnings

This medication contains siltuximab. Do not take Sylvant if you are allergic to siltuximab or any ingredients contained in this drug.

Contraindications

• Severe hypersensitivity

Effects of Drug Abuse

• No information is available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Siltuximab?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Siltuximab?"

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 premedication 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

There are no adequate or well-controlled studies of siltuximab in pregnant women. In animal reproduction studies, administration of a human antibody to IL-6 to pregnant cynomolgus monkeys caused decreases in globulin levels in pregnant animals and the offspring; the drug crossed the placenta in monkeys.

Infants born to pregnant women receiving therapy may be at increased risk of infection, and caution is advised in the administration of live vaccines to these infants; siltuximab therapy should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus; advise patients of childbearing potential to avoid pregnancy.