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. Both heavy chains of canakinumab contain oligosaccharide chains linked to the protein backbone at asparagine 298 (Asn 298). Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1alpha or IL-1 receptor antagonist (IL-1ra). Canakinumab is marketed under the brand name Ilaris and indicated for patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA). Clinical trials have established the administration of canakinumab every 2 weeks to be safe and effective, offering a considerable advantage over the existing treatment with the human IL-1 receptor antagonist, anakinra, which must be injected daily and which is often poorly tolerated by patients.
|Protein chemical formula||C6452H9958N1722O2010S42|
|Protein average weight||145200.0000|
>8836_H|canakinumab|Homo sapiens||H-GAMMA-1 (VH(1-118)+CH1(119-216)+HINGE-REGION(217-231)+CH2(232-341)+CH3(342-448))|||||||448||||MW 49253.6|MW 49253.6|
>8836_L|canakinumab|Homo sapiens||L-KAPPA (V-KAPPA(1-107)+C-KAPPA(108-214))|||||||214||||MW 23357.9|MW 23357.9|
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECDownload FASTA Format
|ACZ-885||Not Available||Not Available|
|ACZ885||Not Available||Not Available|
|Name||Dosage||Strength||Route||Labeller||Marketing Start||Marketing End|
|Ilaris||injection, powder, lyophilized, for solution||150 mg/mL||subcutaneous||Novartis Pharmaceuticals Corporation||2009-06-18||Not Available|
|Ilaris||powder for solution||150 mg||subcutaneous||Novartis Pharmaceuticals Canada Inc||Not Available||Not Available|
|Generic Prescription Products||Not Available|
|Over the Counter Products||Not Available|
|International Brands||Not Available|
|Brand mixtures||Not Available|
|Super Class||Organic Acids|
|Class||Carboxylic Acids and Derivatives|
|Sub Class||Amino Acids, Peptides, and Analogues|
|Alternative Parents||Not Available|
|Molecular Framework||Not Available|
|External Descriptors||Not Available|
|Indication||Used in patients 4 years of age and older to treat Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), which are both part of the Cryopyrin-Associated Periodic Syndromes (CAPS) as well as for patients 2 years of age and older to treat systemic juvenile idiopathic arthritis (SJIA). |
|Pharmacodynamics||Novartis AG has developed canakinumab as a subcutaneous injection and fully human mAb that neutralizes the bioactivity of human IL-1beta, which is involved in several inflammatory disorders. Canakinumab has promising clinical safety and pharmacokinetic properties, and demonstrated potential for the treatment of cryopyrin-associated periodic syndromes (CAPS), systemic juvenile idiopathic arthritis (SJIA), and possibly for other complex inflammatory diseases, such as rheumatoid arthritis, COPD disease and ocular diseases. |
|Mechanism of action||In inflammatory diseases involving Cryopyrin-Associated Periodic Syndromes (CAPS), interleukin-1 beta (IL-1β) is excessively activated and drives inflammation. The protein cryopyrin controls the activation of IL-1β, and mutations in cryopyrin's gene, NLRP-3, up-regulate IL-1β activation. Canakinumab is a human monoclonal anti-human IL-1β antibody of the IgG1/κ isotype. Canakinumab binds to human IL-1β and neutralizes its inflammatory activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1α or IL-1 receptor antagonist (IL-1ra).
|Absorption||The absolute bioavailability of subcutaneous canakinumab is estimated to be 70%.|
|Volume of distribution|
- 6.01 L [typical CAPS patient weighing 70 kg]
|Protein binding||Canakinumab binds to plasma IL-1β, but plasma protein binding was not quantified.|
The metabolism of canakinumab is not yet determined.
|Route of elimination||The route of elimination for canakinumab has not yet been determined.|
|Half life||26 days|
- 0.174 L/day [typical CAPS patient weighing 70 kg]
|Toxicity||The most common adverse reactions involved the central nervous system (headache and vertigo), gastrointestinal system (diarrhea and nausea), neuromuscular and skeletal system (musculoskeletal pain), and respiratory system (rhinitis, nasopharyngitis and bronchitis). Influenza was also reported.
|SNP Mediated Effects||Not Available|
|SNP Mediated Adverse Drug Reactions||Not Available|
|Injection, powder, lyophilized, for solution||subcutaneous||150 mg/mL|
|Powder for solution||subcutaneous||150 mg|
|Experimental Properties||Not Available|
|Synthesis Reference||Not Available|
- Church LD, McDermott MF: Canakinumab, a fully-human mAb against IL-1beta for the potential treatment of inflammatory disorders. Curr Opin Mol Ther. 2009 Feb;11(1):81-9. Pubmed
- IMGT Link
- Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN: Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009 Jun 4;360(23):2416-25. Pubmed
- FDA label.
|AHFS Codes||Not Available|
|PDB Entries||Not Available|
|FDA label||Download (120 KB) |
|MSDS||Download (568 KB) |
|Adalimumab||Increases immunosuppressive effects and risk of infection. |
|Alefacept||Increases immunosuppressive effects and risk of infection. |
|Anakinra||results in increased immunosuppressive effects; increases the risk of infection. |
|Antithymocyte globulin||results in increased immunosuppressive effects; increases the risk of infection. |
|Azathioprine||results in increased immunosuppressive effects; increases the risk of infection. |
|Basiliximab||results in increased immunosuppressive effects; increases the risk of infection. |
|Etanercept||Combination should be avoided because Etanercept increase the toxic effects of canakinumab including neutropenia. |
|golimumab||Avoid combination with canakinumab due to the increased chance of neutropenia and/or serious infection.|
|Infliximab||Avoid combination due to increased risk of infection as anti-TNF agents enhance adverse effects of Canakinumab.|
|Natalizumab||Avoid combination due to the increased risk of infection.
|Pimecrolimus||Avoid combination due the potential increase in immunosuppressant adverse effects.
|Rilonacept||results in increased immunosuppressive effects; increases the risk of infection. |
|Tofacitinib||Avoid combination with tofacitinib and other potent immunosuppressants due to potential enhancement of immunosuppressant effects.|
- No food effects were found.