Sylvant
Siltuximab · Injection, Powder, For Solution · Intravenous
Uses
1 INDICATIONS AND USAGE 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. 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. 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 ) 2.1 Recommended Dosage Administer SYLVANT 11 mg/kg over 1 hour as an intravenous infusion every 3 weeks until treatment failure. Perform hematology laboratory tests prior to each dose of SYLVANT therapy for the first 12 months and every 3 dosing cycles thereafter. If treatment criteria outlined in Table 1 are not met, consider delaying treatment with SYLVANT. Do not reduce dose. Table 1: Treatment Criteria Laboratory parameter Requirements before first SYLVANT administration Retreatment criteria Absolute Neutrophil Count ≥1.0 × 10 9 /L ≥1.0 × 10 9 /L Platelet count ≥75 × 10 9 /L ≥50 × 10 9 /L Hemoglobin SYLVANT may increase hemoglobin levels in MCD patients <17 g/dL <17 g/dL Do not administer SYLVANT to patients with severe infections until the infection resolves. Discontinue SYLVANT in patients with severe infusion related reactions, anaphylaxis, severe allergic reactions, or cytokine release syndromes. Do not reinstitute treatment. 2.2 Instructions for Preparation and Administration Use aseptic technique for reconstitution and preparation of dosing solution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit 1. Calculate the dose (mg), total volume (mL) of reconstituted SYLVANT solution required and the number of vials needed. A 21-gauge 1½ inch needle is recommended for preparation. Infusion bags (250 mL) must contain Dextrose 5% in Water and must be made of polyvinyl chloride (PVC), or polyolefin (PO), or polypropylene (PP), or polyethylene (PE). Alternatively PE bottles may be used. 2. Allow the vial(s) of SYLVANT to come to room temperature over approximately 30 minutes. SYLVANT should remain at room temperature for the duration of the preparation. 3. Aseptically reconstitute each SYLVANT vial as instructed in Table 2. Table 2: Reconstitution Instructions Strength Amount of Sterile Water for Injection, USP required for reconstitution Post-reconstitution concentration 100 mg vial 5.2 mL 20 mg/mL 400 mg vial 20 mL 20 mg/mL Gently swirl the reconstituted vials to aid the dissolution of the lyophilized powder. DO NOT SHAKE or SWIRL VIGOROUSLY. Do not remove the contents until all of the solids have been completely dissolved. The lyophilized powder should dissolve in less than 60 minutes. Once reconstituted, and prior to further dilution, inspect the vials for particulates and discoloration. Do not use if particles or solution discoloration are present or if visibly opaque. The reconstituted product should be kept for no more than two hours prior to addition into the infusion bag. 4. Dilute the reconstituted SYLVANT solution dose to 250 mL with sterile Dextrose 5% in Water by withdrawing a volume equal to the total calculated volume of reconstituted SYLVANT from the Dextrose 5% in Water, 250 mL bag. Slowly add the total calculated volume (mL) of reconstituted SYLVANT solution to the Dextrose 5% in Water infusion bag. Gently invert the bag to mix the solution. 5. Administer the diluted SYLVANT solution in 5% Dextrose in Water 250 mL by intravenous infusion over a period of 1 hour using administration sets lined with PVC, or polyurethane (PU), or PE, containing a 0.2-micron inline polyethersulfone (PES) filter. The infusion should be completed within 4 hours of the dilution of the reconstituted solution to the infusion bag. 6. Do not infuse SYLVANT concomitantly in the same intravenous line with other agents. 7. SYLVANT does not contain preservatives. Do not store any unused portion of the reconstituted product or of the infusion solution. Waste material should be disposed of in accordance with local requirements.
Dosage forms and strengths
(siltuximab) for injection is available as: 100 mg of lyophilized powder in a single-dose vial for intravenous infusion. 400 mg of lyophilized powder in a single-dose vial for intravenous infusion. 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 [see Warnings and Precautions (5.3) ] . Hypersensitivity reactions, including anaphylactic reaction, hypersensitivity, and drug hypersensitivity have been reported in patients treated with siltuximab. 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 ) 5.1 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. 5.2 Vaccinations Do not administer live vaccines to patients or infants born to patients receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens [see Use in Specific Populations (8.1) ]. 5.3 Infusion Related Reactions and Hypersensitivity SYLVANT may cause infusion related reactions and anaphylaxis. Approximately 945 patients have been treated with SYLVANT in clinical trials. Of these, one patient experienced an anaphylactic reaction. Data from 254 patients treated with SYLVANT monotherapy forms the basis of the safety evaluation of infusion related reactions. Infusion related reactions were reported in 5.1% of these patients. Two (0.8%) were Grade 3 or higher, and 1 (0.4%) was serious; none were fatal. Symptoms of infusion reactions consisted of back pain, chest pain or discomfort, nausea and vomiting, flushing, erythema, and palpitations. In long-term treatment of MCD patients with siltuximab at the recommended dosage of 11 mg/kg every 3 weeks, infusion related reactions or hypersensitivity reactions occurred at a frequency of 6.3% (1.3% for severe reactions). 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 reaction. 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 (6) ]. Administer SYLVANT in a setting that provides resuscitation equipment, medication, and personnel trained to provide resuscitation. 5.4 Gastrointestinal Perforation 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.
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 (5.1) ] Infusion-related reactions and hypersensitivity [see Warnings and Precautions (5.3) ] Gastrointestinal perforation [see Warnings and Precautions (5.4) ] The most common adverse reactions (>10% of patients) were rash, pruritus, upper respiratory tract infection, increased weight, and hyperuricemia. To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc., at 1-888-575-8344 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 Reactions SYLVANT+BSC Best Supportive Care n=53 Placebo+BSC n=26 All Grades Grades 3-4 All Grades Grades 3-4 Skin disorders Rash (rash, rash generalized, rash maculo-papular, rash popular and rash pruritic) 15 (28%) 1 (2%) 3 (12%) 0 Pruritus 15 (28%) 0 2 (8%) 0 Skin hyperpigmentation 2 (4%) 0 0 0 Eczema 2 (4%) 0 0 0 Psoriasis 2 (4%) 0 0 0 Dry skin 2 (4%) 0 0 0 Infections Lower respiratory tract 4 (8%) 2 (4%) 1 (4%) 1 (4%) Upper respiratory tract 14 (26%) 1 (2%) 4 (15%) 1 (4%) Blood and lymphatic system disorders Thrombocytopenia 5 (9%) 2 (4%) 1 (4%) 1 (4%) General disorders Edema (general and localized) 14 (26%) 4 (8%) 7 (27%) 0 Gastrointestinal disorders Constipation 4 (8%) 0 1 (4%) 0 Metabolism Hypertriglyceridemia 4 (8%) 0 0 0 Hypercholesterolemia 2 (4%) 0 0 0 Hyperuricemia 6 (11%) 1 (2%) 0 0 Respiratory, thoracic and mediastinal disorders Oropharyngeal pain 4 (8%) 0 1 (4%) 0 Renal and urinary disorders Renal impairment 4 (8%) 0 0 0 Nervous system disorders Headache 4 (8%) 0 1 (4%) 0 Investigations Weight increased 10 (19%) 1 (2%) 0 0 Vascular disorders Hypotension 2 (4%) 1 (2%) Anaphylactic reaction 0 0 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 6.2 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.
Drug interactions
7.1 Cytochrome P450 Substrates Cytochrome P450s in the liver are down regulated by infection and inflammation stimuli including cytokines such as IL-6. Inhibition of IL-6 signaling in patients treated with SYLVANT may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates compared to metabolism prior to treatment with SYLVANT. Upon initiation or discontinuation of SYLVANT, in patients being treated with CYP450 substrates with a narrow therapeutic index, perform therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) as needed and adjust dose. The effect of SYLVANT on CYP450 enzyme activity can persist for several weeks after stopping therapy. Exercise caution when SYLVANT is co-administered with CYP3A4 substrate drugs where a decrease in effectiveness would be undesirable (e.g., oral contraceptives, lovastatin, atorvastatin).
Use in specific populations
Pregnancy: May cause fetal harm ( 8.1 ) 8.1 Pregnancy 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. 8.2 Lactation 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. 8.3 Females and Males of Reproductive Potential 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. 8.4 Pediatric Use The safety and efficacy of SYLVANT have not been established in pediatric patients. 8.5 Geriatric Use 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. 8.6 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 (12.3) ]. 8.7 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 (12.3) ].
Pregnancy
8.1 Pregnancy 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.
Pediatric use
8.4 Pediatric Use The safety and efficacy of SYLVANT have not been established in pediatric patients.
Geriatric use
8.5 Geriatric Use 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.
Description
Siltuximab is a human-mouse chimeric monoclonal antibody that binds human interleukin-6 (IL-6) and is produced by Chinese hamster ovary cells. SYLVANT (siltuximab) for injection is supplied as a sterile, white, preservative free, lyophilized powder in single-dose vials. Each SYLVANT 100 mg single-dose vial contains 100 mg siltuximab, 3.7 mg L-histidine (from L-histidine and L-histidine monohydrochloride monohydrate), 0.8 mg polysorbate 80, and 169 mg sucrose. Each SYLVANT 400 mg single-dose vial contains 400 mg siltuximab, 14.9 mg L-histidine (from L-histidine and L-histidine monohydrochloride monohydrate), 3.2 mg polysorbate 80, and 677 mg sucrose. Following reconstitution with Sterile Water for Injection, USP (per section 2.2), the resulting pH is approximately 5.2. The resulting solution contains 20 mg/mL siltuximab to be administered by intravenous infusion following dilution [see Dosage and Administration (2.2) ] .
Mechanism of action
12.1 Mechanism of Action Siltuximab binds human IL-6 and prevents the binding of IL-6 to both soluble and membrane-bound IL-6 receptors. IL-6 has been shown to be involved in diverse normal physiologic processes such as induction of immunoglobulin secretion. Overproduction of IL-6 has been linked to systemic manifestations in patients with MCD.
How supplied
16.1 How Supplied 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: NDC: 73090-420-01 contains one 100 mg vial NDC: 73090-421-01 contains one 400 mg vial 16.2 Storage and Stability 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.
Storage
16.2 Storage and Stability 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.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Instruct the patient of the risks of SYLVANT treatment. Infections 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. Vaccination Inform the patient that they should discuss the recommended vaccinations prior to treatment with SYLVANT. Advise females with infants exposed to SYLVANT in utero to inform the pediatrician of the exposure [see Use in Specific Populations (8.1) ] . Allergic Reactions 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. Pregnancy Advise patients of childbearing potential to avoid pregnancy and to use contraception during treatment and for 3 months after the last dose of SYLVANT. Lactation Advise females not to breastfeed during treatment with SYLVANT and for 3 months after the final dose [see Use in Specific Populations (8.2) ].
Label text from the FDA structured product label by Recordati Rare Diseases, Inc. (revised Aug 27, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Siltuximab in 2 products
Sylvant NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 73090-420 | Siltuximab 100 mg/1 Injection, Powder, For Solution | Recordati Rare Diseases, Inc. | BLA |
| 73090-421 | Siltuximab 400 mg/1 Injection, Powder, For Solution | Recordati Rare Diseases, Inc. | BLA |
Frequently asked questions
What is Sylvant used for?
1 INDICATIONS AND USAGE 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. 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…
What are the side effects of Sylvant?
The following clinically significant adverse reactions are also discussed in other sections of the labeling: Concurrent active severe infections [see Warnings and Precautions (5.1) ] Infusion-related reactions and hypersensitivity [see Warnings and Precautions (5.3) ] Gastrointestinal perforation [see Warnings and Precautions (5.4) ] The most common adverse reactions (>10% of patients) were rash,… See the full label for the complete list.
Who makes Sylvant?
Sylvant is listed by 1 labeler in the FDA NDC directory, including Recordati Rare Diseases, Inc..