Rilonacept
FDA Drug Information • Also known as: Arcalyst
- Brand Names
- Arcalyst
- Dosage Form
- INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
- Product Type
- DRUG FOR FURTHER PROCESSING
Description
11 DESCRIPTION Rilonacept is a dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human interleukin-1 receptor component (IL-1R1) and IL-1 receptor accessory protein (IL-1RAcP) linked in-line to the Fc portion of human IgG1. Rilonacept has a molecular weight of approximately 251 kDa. Rilonacept is expressed in recombinant Chinese hamster ovary (CHO) cells. ARCALYST is supplied in single-dose vials containing a sterile, white to off-white lyophilized powder. Each vial of ARCALYST is to be reconstituted with 2.3 mL of Sterile Water for Injection, USP. A volume of up to 2 mL can be withdrawn, which is designed to deliver 160 mg for subcutaneous administration only. The resulting solution is viscous, clear, colorless to pale yellow, and essentially free from particulates. Each vial contains 220 mg rilonacept. After reconstitution, each vial contains rilonacept (80 mg/mL), glycine (10 mg/mL), histidine (46 mM), L-arginine (50 mM), polyethylene glycol 3350 (30 mg/mL), and sucrose (20 mg/mL) at a pH of 6.5. No preservatives are present.
What Is Rilonacept Used For?
1 INDICATIONS AND USAGE ARCALYST (rilonacept) is an interleukin-1 blocker indicated for: Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS) in adults and children 12 years and older ( 1.1 , 14.1 ) Maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weighing 10 kg or more ( 1.2 , 14.2 ) Treatment of recurrent pericarditis (RP) and reduction in risk of recurrence in adults and children 12 years and older ( 1.3 , 14.3 ) 1.1 Cryopyrin-Associated Periodic Syndromes, Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome ARCALYST ® (rilonacept) is an interleukin-1 blocker indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS), and Muckle-Wells Syndrome (MWS) in adults and pediatric patients 12 years and older. 1.2 Deficiency of IL-1 Receptor Antagonist ARCALYST is indicated for the maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA) in adults and pediatric patients weighing at least 10 kg. 1.3 Recurrent Pericarditis ARCALYST is indicated for the treatment of recurrent pericarditis (RP) and reduction in risk of recurrence in adults and pediatric patients 12 years and older.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Administer by subcutaneous injection ( 2.1 ) CAPS, FCAS, MWS, and RP ( 2.2 ): Adults: – Loading dose: 320 mg, delivered as two 160 mg (2 mL) injections. – Maintenance dose: 160 mg (2 mL) injection once weekly. Pediatric patients 12 years to 17 years: – Loading dose: 4.4 mg/kg, up to a maximum of 320 mg, delivered as 1 or 2 injections (not to exceed 2 mL/injection). – Maintenance dose: 2.2 mg/kg, up to a maximum of 160 mg (2 mL) injection, once weekly. DIRA ( 2.3 ): Adults and pediatric patients weighing 10 kg or more: – 4.4 mg/kg up to a maximum of 320 mg, delivered as 1 or 2 injections (2 mL/injection) once weekly. 2.1 General Dosing Information ARCALYST is for subcutaneous use only. 2.2 Cryopyrin-Associated Periodic Syndromes, Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome and Recurrent Pericarditis Adults : Initiate treatment with a loading dose of 320 mg delivered as two, 2-mL subcutaneous injections of 160 mg each, administered on the same day at two different injection sites. Continue dosing with a once-weekly injection of 160 mg administered as a single, 2-mL subcutaneous injection. Pediatric patients 12 years to 17 years : Initiate treatment with a loading dose of 4.4 mg/kg, up to a maximum dose of 320 mg, administered as one or two subcutaneous injections, not to exceed single-injection volume of 2 mL per injection site. If the initial dose is given as two injections, administer on the same day at two different sites. Continue dosing with a once-weekly injection of 2.2 mg/kg, up to a maximum of 160 mg, administered as a single subcutaneous injection, up to 2 mL. If a once-weekly dose is missed, instruct the patient to administer the injection within 7 days from the missed dose and then resume the patient's original schedule. If the missed dose is not administered within 7 days, instruct the patient to administer the dose, starting a new schedule based on this date. 2.3 Deficiency of IL-1 Receptor Antagonist Adults : The recommended dose of ARCALYST is 320 mg, once weekly, administered as two subcutaneous injections on the same day at two different sites with a maximum single-injection volume of 2 mL. ARCALYST should not be given more often than once weekly. Pediatric patients weighing 10 kg or more : The recommended dose of ARCALYST is 4.4 mg/kg (up to a maximum of 320 mg), once weekly, administered as one or two subcutaneous injections with a maximum single-injection volume of 2 mL. If the dose is given as two injections, administer both on the same day, each one at a different site. When switching from another IL-1 blocker, discontinue the IL-1 blocker and begin ARCALYST treatment at the time of the next dose [see Drug Interactions (7.1) ] . 2.4 Preparation for Administration Reconstitute each single-dose vial of ARCALYST with 2.3 mL of preservative-free Sterile Water for Injection, USP (supplied separately) prior to subcutaneous administration of the drug. 2.5 Administration Using aseptic...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling. Serious Infections [see Warnings and Precautions (5.1) ] Risk of Malignancy [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Lipid Profile Changes [see Warnings and Precautions (5.4) ] The most common adverse reactions reported by patients with CAPS and RP treated with ARCALYST are injection-site reactions and upper respiratory tract infections. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kiniksa at 1-833-KINIKSA (1-833-546-4572) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Clinical trials are conducted under widely varying conditions and, as such, adverse reaction rates observed cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The data described herein reflect exposure to ARCALYST in over 2,000 patients who received at least one dose, including approximately 1700 exposed to 160 mg or more, of whom 151 patients were exposed for at least 6 months and 111 patients for at least one year. These included patients with CAPS and RP, patients with other diseases, and healthy volunteers. CAPS Approximately 60 patients with CAPS were treated weekly with 160 mg of ARCALYST. The pivotal trial population included 47 patients with CAPS. These patients were between the ages of 22 and 78 years (average 51 years). Thirty-one patients were female and 16 were male. All of the patients were White/Caucasian. Six pediatric patients (12 to17 years) were enrolled directly into the open-label extension phase of the trial. Part A of the clinical trial was conducted in patients with CAPS who were naïve to treatment with ARCALYST. Part A of the study was a randomized, double-blind, placebo-controlled, six-week study comparing ARCALYST to placebo [see Clinical Studies (14) ] . Table 1 reflects the frequency of adverse events reported by at least two patients during Part A. Table 1: Most Frequent Adverse Reactions in Patients with CAPS (Part A, Reported by at Least Two Patients) Adverse Event ARCALYST 160 mg (n = 23) Placebo (n= 24) Any AE 17 (74%) 13 (54%) Injection-site reactions 11 (48%) 3 (13%) Upper respiratory tract infection 6 (26%) 1 (4%) Nausea 1 (4%) 3 (13%) Diarrhea 1 (4%) 3 (13%) Sinusitis 2 (9%) 1 (4%) Abdominal pain upper 0 2 (8%) Cough 2 (9%) 0 Hypoesthesia 2 (9%) 0 Stomach discomfort 1 (4%) 1 (4%) Urinary tract infection 1 (4%) 1 (4%) DIRA In a 2-year, open-label study, 6 pediatric patients with DIRA, 3 years to 6 years of age, received a 2.2 to 4.4 mg/kg dose of ARCALYST once weekly [see Clinical Studies (14.2) ] . The safety profile was generally consistent with that seen in patients with CAPS. The most common adverse reactions were upper respiratory infection (6 of 6), rash (5 of 6), otitis media (3 of 6), pharyngitis (3 of 6) and rhinorrhea (3 of 6). RP In the RP phase 3 study, a total of 86 patients received at least one dose of ARCALYST with a median treatment duration of 9 months [see Clinical Studies (14.3) ]. Of the patients, 49 (57%) were female and 37 (43%) were male; 93% were White/Caucasian. The mean age was 44.7 years. Seven patients (8%) were aged 12-17 years old. No new adverse reactions were identified in this study. Adverse Reactions of Special Interest Injection-Site Reactions In patients with CAPS or RP, the most common and consistently reported adverse event associated with ARCALYST was injection-site reaction (ISR). The ISRs included erythema, swelling, pruritus, mass, bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, vesicles, warmth and hemorrhage. Most injection-site reactions lasted for one to two days. Infections During Part A in the CAPS study, the incidence of patients reporting infections was greater with ARCALYST (48%) than with placebo (17%). In Part B, randomized withdrawal, the...
Drug Interactions
7 DRUG INTERACTIONS 7.1 TNF-Blocking Agent and IL-1 Blocking Agent Specific drug interaction studies have not been conducted with ARCALYST. Concomitant administration of another drug that blocks IL-1 with a TNF-blocking agent in another patient population has been associated with an increased risk of serious infections and an increased risk of neutropenia. The concomitant administration of ARCALYST with TNF-blocking agents may also result in similar toxicities and is not recommended [see Warnings and Precautions (5.1) ] . The concomitant administration of ARCALYST with other drugs that block IL-1 has not been studied. Based upon the potential for pharmacologic interactions between rilonacept and a recombinant IL-1ra, concomitant administration of ARCALYST and other agents that block IL-1 or its receptors is not recommended. 7.2 Cytochrome P450 Substrates The formation of CYP450 enzymes is suppressed by increased levels of cytokines (e.g., IL-1) during chronic inflammation. Thus it is expected that for a molecule that binds to IL-1, such as rilonacept, the formation of CYP450 enzymes could be normalized. This is clinically relevant for CYP450 substrates with a narrow therapeutic index, where the dose is individually adjusted (e.g., warfarin). Upon initiation of ARCALYST in patients being treated with these types of medicinal products, therapeutic monitoring of the effect or drug concentration should be performed, and the individual dose of the medicinal product may need to be adjusted.
Contraindications
4 CONTRAINDICATIONS None. None. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Rare pregnancy outcomes reported postmarketing and from clinical trials, with very limited use of ARCALYST in pregnant women, are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There may be risks to the mother and fetus associated with Cryopyrin Associated Periodic Syndromes (CAPS) (see Clinical Considerations ) . In an animal reproduction study, subcutaneous administration of rilonacept to pregnant monkeys during the period of organogenesis was complicated by losses of drug exposure as the study progressed, due to anti-drug antibody formation at all doses, but a dose-related increase in exposure was still evident. There were no treatment-related effects on fetal survival or development of malformations with doses up to 11 times the maximum recommended human dose (MRHD). Increased incidences of lumbar ribs, a skeletal variation, were observed in fetuses at doses approximately 2 times the MRHD and higher that slightly exceeded incidences in both control animals and the historical control database ( see Data ). There were findings of multiple fusion and absence of the ribs and thoracic vertebral bodies and arches in one fetus of the only pregnant monkey with exposure to rilonacept during the later period of gestation associated with a dose approximately 6 times the MRHD ( see Data ). The relationship of these findings in a single fetus to drug treatment was unclear, as these findings were not evident in fetuses from pregnant monkeys that had higher exposures to rilonacept during the period of organogenesis associated with a dose approximately 11 times the MRHD. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in...
Overdosage
10 OVERDOSAGE There have been no reports of overdose with ARCALYST. Maximum weekly doses of up to 320 mg have been administered subcutaneously for up to approximately 18 months in a small number of patients with CAPS and up to 6 months in patients with an unapproved indication in clinical trials without evidence of dose-limiting toxicities. In addition, ARCALYST given intravenously at doses up to 2000 mg monthly in another patient population for up to six months was tolerated without dose-limiting toxicities. The maximum amount of ARCALYST that can be safely administered has not been determined. In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects, and appropriate symptomatic treatment instituted immediately.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING ARCALYST (rilonacept) for injection is supplied as a sterile, white to off-white, preservative-free, lyophilized powder in single-dose vials. Each 220 mg vial of ARCALYST is supplied in a carton containing one vial (NDC 73604-914-01) or four vials (NDC 73604-914-04). Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not use beyond the date stamped on the label. After reconstitution, ARCALYST may be kept at room temperature, protected from light [see Dosage and Administration (2.5) ].
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.