Rilonacept (Monograph)

Brand name: Arcalyst
Drug class: Other Miscellaneous Therapeutic Agents

Medically reviewed by Drugs.com on Jul 28, 2023. Written by ASHP.

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Introduction

Interleukin-1 (IL-1) receptor antagonist (IL-1Ra); dimeric fusion protein.

Uses for Rilonacept

Cryopyrin-associated Periodic Syndromes

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 of age; designated an orphan drug by FDA for use in these conditions.

Guidelines recommend use of IL-1 inhibitors including anakinra, rilonacept, and canakinumab for patients with CAPS.

Deficiency of Interleukin-1 Receptor Antagonist

Maintenance of remission of deficiency of IL-1 receptor antagonist (DIRA) in adult and pediatric patients weighing ≥10 kg.

Designated an orphan drug by FDA for use in this condition.

Guidelines recommend use of IL-1 inhibitors for both diagnosis and treatment of DIRA.

Recurrent Pericarditis

Treatment of recurrent pericarditis and for reduction in the risk of recurrence in adults and pediatric patients ≥12 years of age.

Designated an orphan drug by FDA for use in this condition.

Rilonacept Dosage and Administration

General

Pretreatment Screening

• Confirm absence of chronic or acute infection. Evaluate for, and if necessary, treat latent tuberculosis infection before initiating treatment with rilonacept.

• Ensure that patients receive all recommended vaccinations, including pneumococcal and inactivated influenza vaccines, before initiating treatment with rilonacept.

Patient Monitoring

• Monitor lipid profile 2–3 months after treatment initiation and start antilipemic therapy as needed.

• Monitor for signs and symptoms of infection.

Administration

Sub-Q Administration

Administer by sub-Q injection only; do not give by IM, IV, or intra-arterial injection.

Perform the first injection of rilonacept under the supervision of a clinician; subsequent injections may be self-administered if the clinician determines that the patient and/or their caregiver is competent to safely administer the drug after appropriate training and with medical follow-up as necessary.

Inject sub-Q into the upper arms, thighs, or abdomen (avoid the 2-inch area around the navel); rotate injection sites to prevent irritation and to allow complete absorption of the drug.

Injection sites in the abdomen and thigh are preferred if the patient is administering the drug; if another person is administering the injection, may use the upper arm. Do not inject into areas where the skin is bruised, red, swollen, tender, or hard.

Gently pinch tissue around the injection site and insert needle at a 90° angle (45° angle may be appropriate for small children and thin individuals). After pulling back the plunger to ensure that blood is not aspirated, inject drug at a slow, steady rate; up to 30 seconds may be required to inject the entire dose.

Divide doses exceeding 160 mg (2 mL) equally into 2 syringes and inject on the same day into 2 separate sites.

Reconstitution

Reconstitute the appropriate number of vials of the drug based on the indicated dosage of rilonacept.

Prior to administration, reconstitute rilonacept lyophilized powder for injection using proper aseptic technique by adding 2.3 mL of preservative-free sterile water for injection (using a 3-mL syringe with a 27-gauge, ½-inch needle) to a vial labeled as containing 220 mg of rilonacept to provide a solution containing 80 mg/mL.

Hold the vial sideways (not upright) and shake back and forth (side-to-side) for approximately one minute, then allow to sit for one minute. If the powder is not completely dissolved, shake the vial for approximately 30 seconds more and then allow to sit for one minute; repeat the process until the powder is completely dissolved and the solution is clear. The reconstituted solution should be viscous, clear, colorless to pale yellow, and essentially free from particulates.

Discard the needle and syringe used for reconstitution; do not use for sub-Q injection.

Before administration, withdraw the appropriate dose of rilonacept (up to 160 mg or 2 mL) into a new 3-mL syringe using a new 27-gauge, ½-inch needle. Discard unused portions of the reconstituted solution since the solution contains no preservatives.

Dosage

Pediatric Patients

Cryopyrin-associated Periodic Syndromes

Sub-Q

Usual loading dose in pediatric patients 12–17 years of age: 4.4 mg/kg (up to 320 mg) given as 1 or 2 injections (maximum 160 mg [2 mL] per injection).

Usual maintenance dosage in pediatric patients 12–17 years of age: 2.2 mg/kg (up to 160 mg) given as a single injection once weekly beginning 1 week after the loading dose.

Safety and efficacy of lower doses or longer dosing intervals not established.

If a once-weekly dose is missed, administer injection within 7 days from missed dose and resume original schedule. If missed dose is not administered within 7 days, administer the dose, starting a new schedule based on this date.

Deficiency of IL-1 Receptor Antagonist

Sub-Q

Pediatric patients weighing ≥10 kg: 4.4 mg/kg (up to 320 mg) given as 1 or 2 injections (maximum 2 mL per injection) once weekly.

When switching from another IL-1 blocker, discontinue the IL-1 blocker and begin rilonacept treatment at the time of the next dose.

Recurrent Pericarditis

Sub-Q

Usual loading dose in pediatric patients 12–17 years of age: 4.4 mg/kg (up to 320 mg) given as 1 or 2 injections (maximum 160 mg [2 mL] per injection).

Usual maintenance dosage in pediatric patients 12–17 years of age: 2.2 mg/kg (up to 160 mg) given as a single injection once weekly beginning 1 week after the loading dose.

If a once-weekly dose is missed, administer injection within 7 days from missed dose and resume original schedule. If missed dose is not administered within 7 days, administer the dose, starting a new schedule based on this date.

Adults

Cryopyrin-associated Periodic Syndromes

Sub-Q

Usual loading dose: 320 mg given as 2 divided injections of 160 mg each.

Usual maintenance dosage: 160 mg given as a single injection once weekly beginning 1 week after the loading dose.

Safety and efficacy of lower doses or longer dosing intervals not established.

If a once-weekly dose is missed, administer injection within 7 days from missed dose and resume original schedule. If missed dose is not administered within 7 days, administer the dose, starting a new schedule based on this date.

Deficiency of IL-1 Receptor Antagonist

Sub-Q

320 mg once weekly (given as 2 injections of 160 mg [2 mL] each on the same day at 2 different sites).

When switching from another IL-1 blocker, discontinue the IL-1 blocker and begin rilonacept treatment at the time of the next dose.

Recurrent Pericarditis

Sub-Q

Usual loading dose: 320 mg given as 2 divided injections of 160 mg each.

Usual maintenance dosage: 160 mg given as a single injection once weekly beginning 1 week after the loading dose.

If a once-weekly dose is missed, administer injection within 7 days from missed dose and resume original schedule. If missed dose is not administered within 7 days, administer the dose, starting a new schedule based on this date.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Related/similar drugs

anakinra, Kineret, canakinumab, Arcalyst, Ilaris

Cautions for Rilonacept

Contraindications

• None.

Warnings/Precautions

Serious Infections

IL-1 blockade may interfere with immune response to infections. Increased incidence of infections reported, including serious, potentially life-threatening infections (e.g., Mycobacterium intracellulare infection, sinusitis, and bronchitis, Streptococcus pneumoniae meningitis).

Infections may occur at any time during therapy. Do not initiate rilonacept in patients with an active or chronic infection; discontinue therapy in patients who develop a serious infection. Do not use with tumor necrosis factor inhibitors due to the increased risk of serious infections.

May increase risk of tuberculosis or other atypical or opportunistic infections. Evaluate and treat patients for latent tuberculosis prior to initiation of rilonacept therapy.

Risk of Malignancy

Effect on active and/or chronic infections and on development of malignancies not known. However, possible increased risk of malignancies with treatment with immunosuppressive agents, including rilonacept.

Hypersensitivity Reactions

Hypersensitivity reactions reported rarely. If hypersensitivity reactions (e.g., rash, swollen face, difficulty breathing) occur, discontinue rilonacept and initiate appropriate therapy.

Lipid Profile Changes

Increases in total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations reported. Monitor lipoprotein concentrations and initiate antilipemic therapy as needed based on cardiovascular risk factors and current clinical guidelines.

Immunizations

Vaccine efficacy may be reduced; avoid live vaccines during rilonacept therapy.

Review vaccination status of all patients and administer all age-appropriate vaccines, including pneumococcal vaccine and influenza virus vaccine inactivated, prior to initiation of rilonacept therapy.

Immunogenicity

In patients with recurrent pericarditis, anti-drug antibodies, including neutralizing antibodies, detected. No correlation between antibody activity and effectiveness or safety.

Specific Populations

Pregnancy

The risk of rilonacept use during human pregnancy is unknown. Limited data to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Fetal malformations reported in some animal studies of rilonacept administration above maximum recommended human dose; unclear whether these are related to drug treatment.

Lactation

Not known whether rilonacept is distributed into human or animal milk. Caution if used in nursing women. Consider benefits of breastfeeding to infant and benefit of treatment to mother.

Pediatric Use

Safety and efficacy not established in children <12 years of age with CAPS or recurrent pericarditis.

Safety and efficacy not established in pediatric patients weighing <10 kg for maintenance of remission of DIRA.

In animal studies, rilonacept may have contributed to alterations in bone ossification in the fetus; not known if rilonacept will affect bone development in pediatric patients. Monitor pediatric patients for growth and development.

Geriatric Use

Efficacy, safety, and tolerability profile in those ≥65 years of age generally similar to that in younger adults. Age did not appear to impact steady-state trough concentrations. Fatal bacterial meningitis reported in a 71-year-old woman in a clinical study.

Hepatic Impairment

Pharmacokinetics not evaluated in patients with hepatic impairment.

Renal Impairment

Pharmacokinetics not evaluated in patients with renal impairment.

Common Adverse Effects

The most common adverse reactions reported by patients with CAPS and recurrent pericarditis are injection-site reactions and upper respiratory tract infection.

Drug Interactions

No formal drug interaction studies to date.

Drugs Metabolized by Hepatic Microsomal Enzymes

Increased levels of cytokines (e.g., IL-1) during chronic inflammation suppress the formation of CYP isoenzymes; drugs that bind to IL-1, including rilonacept, are expected to normalize CYP enzyme formation.

If rilonacept is initiated in a patient already receiving a CYP isoenzyme substrate that has a narrow therapeutic margin, monitor efficacy or concentrations of the concomitant drug and adjust dosage of the concomitant drug as needed.

Vaccines

Data not available on the effects of live virus vaccines in patients receiving rilonacept; administration of live vaccines not recommended. Data not available regarding whether rilonacept would affect the rate of secondary transmission of vaccine virus following administration of a live virus vaccine or regarding any other effect of vaccination on patients receiving the drug.

Specific recommendations regarding the length of time to wait between discontinuance of rilonacept and administration of a live vaccine or the length of time to wait between administration of a live vaccine and initiation of rilonacept therapy not available.

Prior to initiation, ensure adult and pediatric patients receive all recommended vaccinations, including pneumococcal and inactivated influenza vaccines.

Specific Drugs

Rilonacept Pharmacokinetics

Absorption

Bioavailability

Relative bioavailability following sub-Q administration is approximately 50%. Peak plasma concentrations achieved in approximately 3.6 days in healthy individuals. Steady-state concentrations reached by 6 weeks in patients with CAPS and 2 weeks in patients with recurrent pericarditis.

Onset

Improvement in symptom scores occurs within several days following initiation of therapy in most patients.

Special Populations

Following sub-Q administration for 24 weeks in pediatric patients 12–16 years of age with CAPS, mean trough drug concentrations were similar to those observed in adults with CAPS.

No significant difference in steady-state trough concentrations observed between geriatric patients and younger adults.

Distribution

Extent

Not known whether rilonacept is distributed into milk.

Elimination

Half-life

Terminal half-life: 7.72 days.

In vivo circulation half-life approximately 7 days in patients with recurrent pericarditis.

Special Populations

Pharmacokinetic data not available for patients with hepatic impairment.

In patients with end-stage renal disease on hemodialysis, mean concentrations after hemodialysis increased compared to pre-dialysis, but difference considered not clinically important.

Effects of age, gender, or body weight on the pharmacokinetics of rilonacept not systematically evaluated.

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original carton to protect from light.

Following reconstitution, store at room temperature, protect from light, and use within 3 hours. Discard unused portion of vial after a single withdrawal of drug.

Actions

• Dimeric fusion protein consisting of the ligand-binding domains of the extracellular portions of the human IL-1 type I receptor (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP) linked in-line to the Fc portion of human immunoglobulin G₁.

• Blocks IL-1β signaling by acting as a soluble decoy receptor that binds IL-1β and prevents its interaction with cell surface receptors; also binds IL-1α and IL-1Ra to a lesser extent. Mutations in the NLRP-3 gene in patients with CAPS result in an overactive inflammasome, causing excessive release of activated IL-1β.

• Results in sustained reductions in mean concentrations of SAA and CRP, indicators of inflammatory disease activity associated with CAPS, DIRA, and recurrent pericarditis. Elevated SAA concentrations have been associated with the development of systemic amyloidosis in patients with CAPS.

Advice to Patients

• Instruct patients to read the manufacturer’s patient information.

• Instruct patients to discuss any questions pertaining to the manufacturer’s patient information.

• If self-administration is being considered, instruct the patient and/or caregiver regarding proper dosage and administration of rilonacept (including how to divide the total dose if the volume needed is >2 mL, the use of aseptic technique, and safe disposal of vials, needles, and syringes)l.

• Inform patients of the risk of injection site reactions (e.g., erythema, swelling, pruritus, mass, bruising, inflammation, pain, edema, dermatitis, discomfort, urticaria, vesicles, warmth, hemorrhage). Advise patients to not inject into areas where the skin is bruised, red, swollen, tender, or hard. Advise patients to inform a clinician of any persistent injection site reaction.

• Inform patients of the risk of serious, potentially life-threatening infection. Advise patients to inform clinicians promptly if any signs or symptoms of infection (e.g., fever, cough, flu-like symptoms, open sores) occur.

• Advise patients about the risk of hypersensitivity reactions and the importance of immediately contacting a clinician or seeking immediate medical attention if any signs or symptoms of hypersensitivity (e.g., rash, swollen face, difficulty breathing) occur.

• Inform patients of possible changes in blood cholesterol and triglyceride concentrations and the importance of adherence to laboratory appointment schedules.

• Advise patients about the importance of reviewing vaccination status with their clinician and receiving all age-appropriate vaccines prior to initiation of rilonacept therapy.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription (e.g., IL-1 antagonists, TNF-blocking agents, immunizations, corticosteroids) or OTC drugs, dietary supplements, and/or herbal products, as well as any concomitant illnesses (e.g., active or chronic infections, asthma, diabetes mellitus).

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Rilonacept can only be obtained through designated specialty pharmacies and distributors. Contact manufacturer for additional information regarding the Kiniksa OneConnect program (1-781-609-7826).

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