"The U.S. Food and Drug Administration yesterday approved Ruconest, the first recombinant C1-Esterase Inhibitor product for the treatment of acute attacks in adult and adolescent patients with hereditary angioedema (HAE).
Concurrent Active Severe Infections
Do not administer SYLVANT to patients with severe infections until the infection resolves. SYLVANT may mask signs and symptoms of acute inflammation including suppression of fever and of acute phase reactants such as C-reactive protein (CRP). Monitor patients receiving SYLVANT closely for infections. Institute prompt anti-infective therapy and do not administer further SYLVANT until the infection resolves.
Infusion Related Reactions And Hypersensitivity
Stop the infusion of SYLVANT if the patient develops signs of anaphylaxis. Discontinue further therapy with SYLVANT.
Stop the infusion if the patient develops a mild to moderate infusion reactions. If the reaction resolves, the SYLVANT infusion may be restarted at a lower infusion rate. Consider medication with antihistamines, acetaminophen, and corticosteroids. Discontinue SYLVANT if the patient does not tolerate the infusion following these interventions [see ADVERSE REACTIONS].
Administer SYLVANT in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation.
Gastrointestinal (GI) perforation has been reported in clinical trials although not in MCD trials. Use with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with symptoms that may be associated or suggestive of GI perforation.
Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION).
Patients or their caregivers should be advised of the potential benefits and risks of SYLVANT.
Physicians should instruct their patients to read the patient labeling before starting SYLVANT therapy and to reread it each time they receive an infusion. It is important that the patient's overall health be assessed at each treatment visit and that any questions resulting from the patient's or their caregiver's reading of the patient labeling be discussed.
Inform patients that SYLVANT may lower their resistance to infections. Instruct the patient of the importance of contacting their doctor immediately when symptoms suggesting infection appear in order to assure rapid evaluation and appropriate treatment.
Inform the patient that they should discuss the recommended vaccinations prior to treatment with SYLVANT.
Advise patients to seek immediate medical attention if they experience any symptoms of serious allergic reactions during the infusion. Signs include: difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash.
Advise patients of childbearing potential to avoid pregnancy which may include use of contraception during treatment and for 3 months after SYLVANT therapy.
Other Medical Conditions
Advise patients to report any signs of new or worsening medical conditions.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No carcinogenicity or genotoxicity studies have been conducted with siltuximab.
Two fertility studies were conducted. In one study, drug-treated male mice were mated with untreated females and in the second study drug-treated female mice were mated with untreated males. A murine analog of siltuximab was administered subcutaneously at doses up to 100 mg/kg/week for a total of 7 doses in both studies. There was no effect on male or female fertility parameters. In addition, siltuximab did not produce any toxicity in the reproductive organs in cynomolgus monkeys in the 6-month repeat-dose toxicology study at doses up to 46 mg/kg (approximately 7 times) the systemic exposure in patients at the recommended dose.
Use In Specific Populations
Pregnancy Category C
There are no adequate or well-controlled studies in pregnant women. In animal reproduction studies, administration of siltuximab to pregnant cynomolgus monkeys caused decreases in globulin levels in pregnant animals and in the offspring. Siltuximab crossed the placenta in monkeys. Infants born to pregnant women treated with siltuximab may be at increased risk of infection, and caution is advised in the administration of live vaccines to these infants. Siltuximab 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. Women of childbearing potential should use contraception during and for 3 months after treatment.
In an embryo-fetal development study, siltuximab doses of 9.2 or 46 mg/kg/week were administered intravenously to pregnant monkeys 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 25th administration were approximately 3 and 7 times respectively the exposure in humans at the recommended dose of 11 mg/kg. There was no siltuximab-related maternal or fetal toxicity. 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, cynomolgus monkeys were intravenously administered 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 was evaluated up to 7 months after birth for developmental effects. No maternal or infant toxicity was 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.
It is not known whether siltuximab is excreted in human milk or absorbed systemically after ingestion. Because many drugs and immunoglobulins are excreted in human milk, and because of the potential for adverse reactions in nursing infants from SYLVANT, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
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.
Patients With Renal Impairment
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].
Patients With Hepatic Impairment
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].
Last reviewed on RxList: 5/12/2014
This monograph has been modified to include the generic and brand name in many instances.
Additional Sylvant Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.