Skip to Content

Rilonacept

Pronunciation

(ri LON a sept)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Subcutaneous [preservative free]:

Arcalyst: 220 mg (1 ea) [contains polyethylene glycol]

Brand Names: U.S.

  • Arcalyst

Pharmacologic Category

  • Interleukin-1 Inhibitor

Pharmacology

Cryopyrin-associated periodic syndromes (CAPS) refers to rare genetic syndromes caused by mutations in the nucleotide-binding domain, leucine rich family (NLR), pyrin domain containing 3 (NLRP-3) gene or the cold-induced autoinflammatory syndrome-1 (CIAS1) gene. Cryopyrin, a protein encoded by this gene, regulates interleukin-1 beta (IL-1β) activation. Deficiency of cryopyrin results in excessive inflammation. Rilonacept reduces inflammation by binding to IL-1β (some binding of IL-1α and IL-1 receptor antagonist) and preventing interaction with cell surface receptors.

Onset of Action

Steady state reached by 6 weeks

Half-Life Elimination

8.6 days (Miyamae 2012)

Use: Labeled Indications

Cryopyrin-associated periodic syndromes: For the treatment of cryopyrin-associated periodic syndromes, including familial cold autoinflammatory syndrome and Muckle-Wells syndrome in adults and children 12 years and older.

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Dosage

Cryopyrin-associated periodic syndromes: SubQ:

Children ≥12 years and Adolescents <18 years:

Initial: 4.4 mg/kg (maximum loading dose: 320 mg) given as 1 to 2 separate injections (maximum single injection: 160 mg [2 mL]); if multiple injections are necessary, administer on the same day at 2 different sites

Maintenance: 2.2 mg/kg (maximum dose: 160 mg) once weekly. Note: Begin maintenance dose 1 week following loading dose; do not administer more frequently than once weekly.

Adolescents ≥18 years and Adults:

Initial: 320 mg given as 2 separate injections (160 mg [2 mL] per injection) on the same day at 2 different sites

Maintenance: 160 mg once weekly. Note: Begin maintenance dose 1 week following loading dose; do not administer more frequently than once weekly.

Dosage adjustment in renal impairment: There are no dosage adjustments provided in manufacturer’s labeling (has not been studied).

Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in manufacturer’s labeling (has not been studied).

Reconstitution

Reconstitute rilonacept 220 mg powder for injection with 2.3 mL of preservative free SWFI; quickly shake the vial back and forth for 1 minute, then allow solution to sit for 1 minute. If the powder is not completely dissolved, shake the vial for an additional 30 seconds, then allow solution to sit for 1 minute; repeat if necessary until powder is completely dissolved. Each reconstituted vial allows for withdrawal of 2 mL (160 mg) for SubQ administration.

Administration

SubQ: Rotate injection sites (thigh, abdomen, upper arm); injections should never be made at sites that are bruised, red, tender, or hard. If 2 injections are necessary to complete the loading dose, administer at different injection sites on the same day. Discard any unused portion.

Storage

Store intact vials in refrigerator at 2°C to 8°C (36°F to 46°F). Store in original carton; protect from light; do not freeze. Do not shake. After reconstitution, may be stored at controlled room temperature. Protect from light. Use within 3 hours of reconstitution.

Drug Interactions

Anti-TNF Agents: May enhance the adverse/toxic effect of Rilonacept. Avoid combination

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Canakinumab: Interleukin-1 Inhibitors may enhance the adverse/toxic effect of Canakinumab. Whether such a combination will also alter the therapeutic response to one or both agents is unclear. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Adverse Reactions

>10%:

Immunologic: Antibody development (35%)

Infection: Increased susceptibility to infection (34% to 48%; incidence higher during winter months)

Local: Injection site reaction (48%; majority mild-moderate; typically lasting 1-2 days; characterized by bleeding, bruising, erythema, induration, inflammation, itching, pain, swelling, urticaria; other local reactions include dermatitis, vesicles)

Respiratory: Upper respiratory tract infection (26%)

1% to 10%:

Central nervous system: Hypoesthesia (9%)

Respiratory: Cough (9%), sinusitis (9%)

<1%, postmarketing, and/or case reports: Bacterial meningitis (Streptococcus pneumoniae), bronchitis, colitis, gastrointestinal hemorrhage, hypercholesterolemia, hypersensitivity reaction, increased HDL cholesterol, increased LDL cholesterol, increased serum triglycerides, mycobacterium infection (Mycobacterium intracellulare), neutropenia (transient)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: May cause rare hypersensitivity reactions; discontinue use and initiate appropriate therapy if reaction occurs.

• Infections: Caution should be exercised when considering use in patients with a history of new/recurrent infections, with conditions that predispose them to infections, or with latent or localized infections. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Therapy should not be initiated in patients with active or chronic infections. May increase risk of reactivation of latent tuberculosis; follow current guidelines for evaluation and treatment of latent tuberculosis prior to initiating rilonacept therapy.

• Malignancy: Use may impair defenses against malignancies; impact on the development and course of malignancies is not fully defined.

Disease-related concerns:

• Hyperlipidemia: Use may increase total cholesterol, HDL, LDL, and triglycerides. Periodic assessment of lipid profile should occur. Initiation of lipid-lowering therapy may be necessary.

Concurrent drug therapy issues:

• Tumor necrosis factor (TNF)-blocking agents: Should not be used in combination with TNF-antagonists. There is an increased risk of serious infection.

Other warnings/precautions:

• Immunizations: Patients should be brought up to date with all immunizations including pneumococcal and influenza vaccines before initiating therapy. Live vaccines should not be given concurrently; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy. Administration of inactivated (killed) vaccines while on therapy may not be effective.

Monitoring Parameters

CBC with differential, lipid profile, C-reactive protein (CRP), serum amyloid A; signs of infection

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience injection site pain, rhinorrhea, rhinitis, or pharyngitis. Have patient report immediately to prescriber signs of infection, severe skin irritation, hematemesis, melena, dyspepsia, skin growths, or injection site irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide