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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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 and Administration
Dosing: Adult
Cryopyrin-associated periodic syndromes: SubQ:
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.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Cryopyrin-associated periodic syndromes (CAPS):
Children ≥12 years and Adolescents ≤17 years:
Initial: SubQ: Loading dose 4.4 mg/kg; maximum dose: 320 mg/dose; Note: Loading dose may be divided into 1 or 2 separate injections administered on same day at different sites; maximum injection volume: 2 mL (160 mg)/injection
Maintenance dose: Begin 1 week after loading dose: SubQ: 2.2 mg/kg/dose once weekly; maximum dose: 160 mg/dose; Note: Do not administer more frequently than once weekly.
Adolescents ≥18 years:
Initial: Loading dose: 320 mg administered as 2 separate injections (160 mg each) on the same day at different sites
Maintenance: Begin 1 week after loading dose: 160 mg once weekly; Note: Do not administer more frequently than once weekly.
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
Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification
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
Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. 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
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification
Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
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. Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination
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. Exceptions: Smallpox and Monkeypox Vaccine (Live). 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
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 common cold symptoms, cough, or runny nose. Have patient report immediately to prescriber signs of infection; numbness or tingling feeling; vomiting blood; black, tarry, or bloody stools; abdominal pain; or severe 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 health care 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.
