Sylvant

Last reviewed on RxList: 6/22/2020
Sylvant Side Effects Center

What Is Sylvant?

Sylvant (siltuximab) is a human-mouse chimeric monoclonal antibody used to treat patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.

What Are Side Effects of Sylvant?

Common side effects of Sylvant include:

Dosage for Sylvant

The dose of Sylvant is 11 mg/kg given over 1 hour as an intravenous infusion administered every 3 weeks until treatment failure.

What Drugs, Substances, or Supplements Interact with Sylvant?

Sylvant may interact with warfarin, cyclosporine, theophylline, oral contraceptives, lovastatin, and atorvastatin. Tell your doctor all medications and supplements you use.

Sylvant During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Sylvant. It is unknown if this drug will harm a fetus. Use birth control during treatment with Sylvant and for 3 months after stopping treatment. It is unknown if this drug passes into breast milk. Breastfeeding while using Sylvant is not recommended.

Additional Information

Our Sylvant (siltuximab) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Sylvant Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; chest tightness, difficult breathing; swelling of your face, lips, tongue, or throat.

Some side effects may occur during the injection. Tell your caregiver right away if you feel nauseated, or have back pain, warmth or redness under your skin, chest pain, pounding heartbeats, fluttering in your chest, or swelling in your face.

Call your doctor at once if you have:

  • bloody or tarry stools, cough with bloody mucus or vomit that looks like coffee grounds;
  • signs of infection, such as fever, chills, painful mouth sores, pain when swallowing, cold or flu symptoms, cough, trouble breathing; or
  • signs of a kidney problem--little or no urination; painful or difficult urination; swelling in your feet or ankles; severe pain in your side or lower back.

Common side effects may include:

  • weight gain;
  • itching or rash;
  • cold symptoms such as stuffy nose, sneezing, sore throat; or
  • high levels of uric acid in your blood (can lead to kidney problems or gout symptoms such as joint stiffness, pain, or swelling).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Sylvant (Siltuximab Injection, for Intravenous Infusion)

Sylvant Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are also discussed in other sections of the labeling:

  • Concurrent active severe infections [see WARNINGS AND PRECAUTIONS]
  • Infusion-related reactions and hypersensitivity [see WARNINGS AND PRECAUTIONS]
  • Gastrointestinal perforation [see WARNINGS AND PRECAUTIONS]

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 trials of another drug and may not reflect the rates observed in clinical practice.

Study 1, in MCD, was an international, multicenter, randomized Phase 2 study of every 3 week infusions comparing SYLVANT and best supportive care (BSC) to placebo and BSC. There were 53 patients randomized to the SYLVANT arm at a dosage of 11 mg/kg and 26 patients randomized to the placebo arm. Of the 26 placebo-treated patients, 13 patients subsequently crossed-over to receive SYLVANT. The median age was 48 years (range 20 to 78), 66% male, 48% Asian, 39% White, 4% Black or African American, 7% other. The patients randomized to SYLVANT received a median of 19 infusions (range 1 to 50) compared to patients randomized to placebo who received a median of 8 infusions (range 2 to 32). To control for disparate exposure between arms, Table 3 reports the per patient incidence of adverse reactions that occurred during the first 8 infusions. Adverse reactions that occurred >3% in the SYLVANT arm are presented.

The most common adverse reactions (> 10% compared to placebo) during treatment with SYLVANT in the MCD clinical trial were rash, pruritus, upper respiratory tract infection, increased weight, and hyperuricemia.

Table 3: Per Patient Incidence of Common Adverse Reactions in Study 1 During Initial 8 Infusions

Body System/Adverse ReactionsSYLVANT + BSCa
n=53
Placebo+BSC
n=26
All GradesGrades 3-4All GradesGrades 3-4
Skin disorders
  Rash (rash, rash generalized, rash maculopapular, rash popular and rash pruritic)15 (28%)1 (2%)3 (12%)0
  Pruritus15 (28%)02 (8%)0
  Skin hyperpigmentation2 (4%)000
  Eczema2 (4%)000
  Psoriasis2 (4%)000
  Dry skin2 (4%)000
Infections
  Lower respiratory tract4 (8%)2 (4%)1 (4%)1 (4%)
  Upper respiratory tract14 (26%)1 (2%)4 (15%)1 (4%)
Blood and lymphatic system disorders
  Thrombocytopenia5 (9%)2 (4%)1 (4%)1 (4%)
General disorders
  Edema (general and localized)14 (26%)4 (8%)7 (27%)0
Gastrointestinal disorders
  Constipation4 (8%)01 (4%)0
Metabolism
  Hypertriglyceridemia4 (8%)000
  Hypercholesterolemia2 (4%)000
  Hyperuricemia6 (11%)1 (2%)00
Respiratory, thoracic and mediastinal disorders
  Oropharyngeal pain4 (8%)01 (4%)0
Renal and urinary disorders
  Renal impairment4 (8%)000
Nervous system disorders
  Headache4 (8%)01 (4%)0
Investigations
  Weight increased10 (19%)1 (2%)00
Vascular disorders
  Hypotension2 (4%)1 (2%)b00
a Best Supportive Care
b Anaphylactic reaction

Study CNTO328MCD2002 (referred to as Study 2) (NCT01400503) was an open label, long term extension study of patients with MCD treated on prior trials. The median duration of siltuximab treatment was 5.52 years (range: 0.8 to 10.8 years); more than 50% of patients received siltuximab treatment for ≥5 years. The rate of serious or Grade ≥3 adverse events did not increase over time as a function of cumulative exposure.

Other important adverse reactions reported in MCD clinical studies, all of which were very common, were:

Infections and infestations: nasopharyngitis, urinary tract infection

Blood and lymphatic system disorders: neutropenia

Nervous system disorders: dizziness

Vascular disorders: hypertension

Gastrointestinal disorders: nausea, abdominal pain, vomiting, diarrhea, gastroesophageal reflux disease, mouth ulceration

Immunogenicity

Immunogenicity data are highly dependent on the sensitivity and specificity of the test methods used. Additionally, the observed incidence of a positive result in a test method may be influenced by several factors, including sample handling, timing of sample collection, drug interference, concomitant medication and the underlying disease. Therefore, comparison of the incidence of antibodies to SYLVANT with the incidence of antibodies to other products may be misleading. The clinical significance of anti-siltuximab antibodies following treatment with SYLVANT is not known.

The immunogenicity of siltuximab has been evaluated using antigen-bridging enzyme immunoassay (EIA) and electrochemiluminescence-based immunoassay (ECLIA) methods. A total of 432 patients across the clinical studies were evaluated at multiple time points for anti-therapeutic antibody (ATA) responses to siltuximab after treatment with SYLVANT. Following SYLVANT dosing, 0/243 (0%) patients tested positive for anti-siltuximab antibodies by EIA and 4/189 (2%) patients tested positive by ECLIA. Further immunogenicity analyses were conducted for all positive samples from the 4 patients with detectable anti-siltuximab antibodies. None of these patients had neutralizing antibodies.

Read the entire FDA prescribing information for Sylvant (Siltuximab Injection, for Intravenous Infusion)

© Sylvant Patient Information is supplied by Cerner Multum, Inc. and Sylvant Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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