Overview
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.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Rilonacept is an interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) cytokine trap. Rilonacept blocks IL-1 signaling by acting as a soluble decoy receptor that binds both IL-1α and IL-1β and prevents its interaction with cell surface receptors. Rilonacept also binds interleukin-1 receptor antagonist (IL-1ra). The equilibrium dissociation constants for rilonacept binding to IL-1α, IL-1β, and IL-1ra were 1.4 pM, 0.5 pM, and 6.1 pM, respectively. CAPS refers to rare genetic syndromes generally caused by mutations in the NLRP-3 [nucleotide-binding domain, leucine rich family (NLR), pyrin domain containing 3] gene (also known as Cold-Induced Autoinflammatory Syndrome-1 [ CIAS1 ]).
Indications
- 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.
Common Doses
- 320 mg
- 160 mg
- 2 mL
- 4.4 mg
Dosage
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.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 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.
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) ] .