Overview
11 DESCRIPTION Canakinumab is a recombinant, human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/κ isotype subclass. It is expressed in a murine Sp2/0-Ag14 cell line and comprised of two 447- (or 448-) residue heavy chains and two 214-residue light chains, with a molecular mass of 145157 Daltons when deglycosylated.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Canakinumab is a human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype. Canakinumab binds to human IL-1β and neutralizes its activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or IL-1 receptor antagonist (IL-1ra). CAPS refer 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]). CAPS disorders are inherited in an autosomal dominant pattern with male and female offspring equally affected. Features common to all disorders include fever, urticaria-like rash, arthralgia, myalgia, fatigue, and conjunctivitis.
Indications
- 1 INDICATIONS AND USAGE ILARIS is an interleukin-1β blocker indicated for the treatment of: • Periodic Fever Syndromes ( 1.1 ): - Cryopyrin-Associated Periodic Syndromes (CAPS), in adults and children 4 years of age and older, including: ◾ Familial Cold Auto-inflammatory Syndrome (FCAS) ◾ Muckle-Wells Syndrome (MWS) - Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS) in adult and pediatric patients - Hyperimmunoglobulin D Syndrome (HIDS)/ Mevalonate Kinase Deficiency (MKD) in adult and pediatric patients - Familial Mediterranean Fever (FMF) in adult and pediatric patients •...
Common Doses
- 150 mg
- 2 mg
- 3 mg
- 300 mg
Dosage
2 DOSAGE AND ADMINISTRATION • CAPS: Recommended weight-based dosage is: - For patients > 40 kg: 150 mg subcutaneously, every 8 weeks - For patients ≥ 15 kg and 40 kg: Starting dosage is 150 mg subcutaneously every 4 weeks. The dosage can be increased to 300 mg every 4 weeks if the clinical response is not adequate. ( 2.3 ) - For patients ≤ 40 kg: Starting dosage is 2 mg/kg subcutaneously every 4 weeks. The dosage can be increased to 4 mg/kg every 4 weeks if the clinical response is not adequate. ( 2.3 ) Still’s disease (AOSD and SJIA): Recommended weight-based dosage for patients ≥ 7.
Contraindications
- 4 CONTRAINDICATIONS Confirmed hypersensitivity to canakinumab or to any of the excipients [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)] . Confirmed hypersensitivity to canakinumab or to any of the excipients. ( 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)] Immunosuppression [see Warnings and Precautions (5.2)] Hypersensitivity Reactions [see Warnings and Precautions (5.3)] Macrophage Activation Syndrome [see Warnings and Precautions (5.5)] CAPS: The most common adverse reactions (>10%) are nasopharyngitis, diarrhea, influenza, rhinitis, nausea, headache, bronchitis, gastroenteritis, pharyngitis, weight increased, musculoskeletal pain, and vertigo.
Interactions
- 7 DRUG INTERACTIONS Interactions between ILARIS and other medicinal products have not been investigated in formal studies. 7.1 TNF-Blocker and IL-1 Blocking Agent An increased incidence of serious infections and an increased risk of neutropenia have been associated with administration of another IL-1 blocker in combination with TNF inhibitors in another patient population. Use of ILARIS with TNF inhibitors may also result in similar toxicities and is not recommended because this may increase the risk of serious infections [ see Warnings and Precautions (5.1) ] .