SYLVANT- siltuximab injection, powder, for solution

Страна: САЩ

Език: английски

Източник: NLM (National Library of Medicine)

Активна съставка:

SILTUXIMAB (UNII: T4H8FMA7IM) (SILTUXIMAB - UNII:T4H8FMA7IM)

Предлага се от:

EUSA Pharma (UK) Ltd

Начин на приложение:

INTRAVENOUS

Вид предписание :

PRESCRIPTION DRUG

Терапевтични показания:

SYLVANT is indicated 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. Limitations of Use SYLVANT was not studied in patients with MCD who are HIV positive or HHV-8 positive because SYLVANT did not bind to virally produced IL-6 in a nonclinical study. Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT [see Warnings and Precautions (5.3)] . Hypersensitivity reactions, including anaphylactic reaction, hypersensitivity, and drug hypersensitivity have been reported in patients treated with siltuximab. Risk-Summary In an animal reproduction study, intravenous administration of a human antibody to IL-6 to pregnant monkeys from the onset of organogenesis through delivery caused functional impairment in pregnant animals and in the offspring. Siltuximab and the human antibody to IL-6 crossed the placenta in monkeys ( see Data ). The limited available information on SYLVANT use during pregnancy is not sufficient to inform a drug-associated risk of major birth defects or miscarriage. Infants born to pregnant women treated with SYLVANT may be at increased risk of infection (see Clinical Considerations). Advise pregnant women of the potential risk to a fetus. The estimated background risk for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Clinical Considerations Fetal/Neonatal adverse reactions Monoclonal antibodies are transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Infants born to pregnant women treated with SYLVANT may be at increased risk of infection. Consider the risks and benefits of administering live or live-attenuated vaccines to infants exposed to SYLVANT in utero [see Warnings and Precautions (5.2)] . Data Animal Data In an embryo-fetal development study in cynomolgus monkeys, pregnant animals received intravenous doses of siltuximab of 9.2 or 46 mg/kg/week during gestation days (GD) 20 to 118, which includes the period of organogenesis. Fetuses were evaluated on GD 140, approximately 25 days prior to the natural birth. Exposures at the low and high dose after the 25 th administration were approximately 3 and 7 times, respectively, the human exposure based on AUC in patients with MCD at the recommended dose of 11 mg/kg every three weeks. No maternal or fetal structural abnormalities were observed. However, siltuximab crossed the placenta at both doses and when measured on GD 140, fetal serum concentrations of siltuximab were similar to maternal concentrations. In a combined embryofetal and pre- and post-natal development study in cynomolgus monkeys, pregnant animals received intravenous doses of 10 or 50 mg/kg/week of a human antibody to IL-6 from GD 20 to natural delivery (GD 167). The offspring were evaluated up to 7 months after birth for developmental effects. No maternal or infant structural abnormalities were observed; however, globulin levels were decreased in pregnant animals (GD 34 through lactation day 30) and in the offspring (lactation days 30-120) at both doses. Risk Summary There are no data on the presence of siltuximab in human milk, the effects on the breastfed child, or the effects on milk production. However, low levels of the human antibody to IL-6 was present in the milk of lactating cynomolgus monkeys. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the potential for serious adverse reactions in the breastfed child including gastrointestinal perforations, advise patients that breastfeeding is not recommended during treatment with SYLVANT, and for 3 months after the last dose. Contraception Females SYLVANT may cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)] . Advise female patients of reproductive potential to use effective contraception during treatment with SYLVANT and for 3 months after the last dose. The safety and efficacy of SYLVANT have not been established in pediatric patients. Of the patients treated with SYLVANT monotherapy in clinical studies 127 (35%) were 65 years and older. No overall differences in safety profile were observed between these patients and younger patients, and other reported clinical experience has not identified differences in the safety profile between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Clinical studies did not include sufficient numbers of patients aged 65 years and older to determine the effect of age on efficacy in MCD population. Based on a population pharmacokinetic analysis using data from clinical trials in patients, no significant difference in siltuximab clearance was observed in patients with pre-existing renal impairment (creatinine clearance (CLCr) ≥ 15 mL/min) compared to patients with baseline normal renal function (CLCr ≥ 90 mL/min). No initial dosage adjustment is necessary for patients with CLCr ≥ 15 mL/min. The potential effect of end stage renal disease on siltuximab pharmacokinetics cannot be determined [see Clinical Pharmacology (12.3)]. Based on a population pharmacokinetic analysis using data from clinical trials in patients, no significant difference in siltuximab clearance was observed in patients with pre-existing mild to moderate hepatic impairment (Child-Pugh Class A and B, respectively) compared to patients with baseline normal hepatic function. 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 [see Clinical Pharmacology (12.3)].

Каталог на резюме:

SYLVANT (siltuximab) for injection is supplied as a sterile, white, preservative free, lyophilized powder in single-dose vials. Each SYLVANT vial is individually packaged in a carton: SYLVANT must be refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not use SYLVANT beyond the expiration date (EXP) located on the carton and the vial.

Статус Оторизация:

Biologic Licensing Application

Данни за продукта

SYLVANT- SILTUXIMAB INJECTION, POWDER, FOR SOLUTION
EUSA PHARMA (UK) LTD
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
SYLVANT
SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR SYLVANT.
SYLVANT (SILTUXIMAB) FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2014
INDICATIONS AND USAGE
SYLVANT is an interleukin-6 (IL-6) antagonist indicated 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. ( 1)
Limitations of Use
SYLVANT was not studied in patients with MCD who are HIV positive or
HHV-8 positive because SYLVANT
did not bind to virally produced IL-6 in a nonclinical study.
DOSAGE AND ADMINISTRATION
For intravenous infusion only.
Administer as an 11 mg/kg dose given over 1 hour by intravenous
infusion every 3 weeks. ( 2)
DOSAGE FORMS AND STRENGTHS
For injection
100 mg of lyophilized powder in a single-dose vial. ( 3)
400 mg of lyophilized powder in a single-dose vial. ( 3)
CONTRAINDICATIONS
Severe hypersensitivity reaction to siltuximab or any of the
excipients in SYLVANT. ( 4)
WARNINGS AND PRECAUTIONS
Concurrent Active Severe Infections: Do not administer SYLVANT to
patients with severe infections,
monitor for infections, institute prompt treatment, and interrupt
SYLVANT until resolution of infection. (
2, 5.1)
Vaccinations: Do not administer live vaccines because IL-6 inhibition
may interfere with the normal
immune response to new antigens. ( 5.2)
Infusion Related Reactions: Administer SYLVANT in a setting that
provides resuscitation equipment,
medication, and personnel trained to provide resuscitation. ( 5.3,
6.1)
Gastrointestinal (GI) perforation: Promptly evaluate patients
presenting with symptoms that may be
associated or suggestive of GI perforation. ( 5.4)
ADVERSE REACTIONS
The most common adverse reactions (>10% of patients) were rash,
pruritus, upper respiratory tract
infection, increased weight, and hyper