SYLVANT(siltuximab)
siltuximab - Drug Summary
CLASSES
Interleukin Inhibitors
DEA CLASS
Rx
DESCRIPTION
Monoclonal antibody that binds human IL-6
Used for the treatment of patients with multicentric Castleman disease who are HIV and HHV-8 negative
Severe infusion-related reactions including anaphylaxis may occur; administer in a setting that has resuscitation equipment and medication
COMMON BRAND NAMES
Sylvant
HOW SUPPLIED
Sylvant Intravenous Inj Pwd F/Sol: 100mg, 400mg
DOSAGE & INDICATIONS
For the treatment of patients with multicentric Castleman's disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative.
NOTE: The FDA has designated siltuximab as an orphan drug for Castleman disease.
Intravenous dosage
Adults
11 mg/kg IV over 1 hour every 3 weeks until treatment failure. Therapy interruption and/or discontinuation may be necessary if severe toxicity occurs. The response (complete response (CR) plus partial response (PR)) rate with improvement or stabilization of disease-related symptoms for at least 18 weeks (primary endpoint) was significantly higher in patients who received siltuximab (n = 53; median duration of therapy, 19 cycles) compared with placebo (n = 26) (34% vs. 0%; p = 0.0012) for the treatment of multicentric Castleman disease in a multinational, randomized, double-blind trial; the median duration of response was 383 days (range, 232 to 676 days). In this study, 55% of patients in the siltuximab arm had received prior systemic therapy. During the study, all patients received best supportive care specified by institutional guidelines. The response rates (eva luated by independent review using modified Cheson criteria) were 39% (CR, n = 2; PR, n = 18) and 4% (PR, n = 1) in the siltuximab and placebo arms, respectively (p = 0.0022); the time to response was 155 days (range, 44 to 742 days) in patients who received siltuximab. The durable symptomatic response rates (based on a disease-related overall symptom score eva luated by investigators) were 57% (n = 30) and 19% (n = 5) in the siltuximab and placebo arms, respectively (p = 0.0018); the time to response was 170 days (range, 67 to 274 days) in patients who received siltuximab. Of note, no patients with the hyaline vascular disease subtype achieved a durable tumor and symptomatic response eva luated by independent review. At a median follow-up of 422 days (range, 55 to 1051 days), the median time to treatment failure was not reached in the siltuximab arm and was 134 days in the placebo arm (p = 0.0084). The 1-year overall survival rate was 100% and 92% in the siltuximab and placebo arms, respectively.
MAXIMUM DOSAGE
Adults
11 mg/kg IV.
Geriatric
11 mg/kg IV.
Adolescents
Safety and efficacy have not been established.
Children
Safety and efficacy have not been established.
Infants
Safety and efficacy have not been established.
Neonates
Safety and efficacy have not been established.
DOSING CONSIDERATIONS
Hepatic Impairment
No initial dosage adjustment is necessary for patients with mild to moderate hepatic impairment. Patients with baseline severe hepatic impairment (Child-Pugh Class C) were not included in clinical trials by the manufacturer.
Renal Impairment
No initial dosage adjustment is necessary for patients with a CrCl >= 15 ml/min. The potential effect of end stage renal disease on siltuximab pharmacokinetics have not been determined.
ADMINISTRATION
Injectable |
