Description

Simple

A medication used to treat inflammatory and autoimmune diseases.

Clinical

An interleukin-1β blocker used to treat Periodic Fever Syndromes such as Cryopyrin-Associated Periodic Syndromes (CAPS) and Familial Mediterranean Fever (FMF), and also to treat active Systemic Juvenile Idiopathic Arthritis (SJIA).

Overview

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.

Pharmacology

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 arthriti... Read more

Pharmacodynamic

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... Read more

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... Read more

Absorption

The absolute bioavailability of subcutaneous canakinumab is estimated to be 70%.

Protein binding

Canakinumab binds to plasma IL-1β, but plasma protein binding was not quantified.

Volume of distribution

6.01 L [typical CAPS patient weighing 70 kg]

Clearance

0.174 L/day [typical CAPS patient weighing 70 kg]

Half life

26 days

Route of elimination

The route of elimination for canakinumab has not yet been determined.

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.... Read more

Adverse Effects

Contraindications

Information currently not available.

Food Interactions

  • Take with or without food.

Interactions

Type in a drug name to check for interaction with Canakinumab
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The metabolism of (R)-warfarin can be increased when combined with Canakinumab.
(S)-Warfarin
The metabolism of (S)-Warfarin can be increased when combined with Canakinumab.
2-Methoxyethanol
The risk or severity of adverse effects can be increased when 2-Methoxyethanol is combined with Canakinumab.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be increased when combined with Canakinumab.
4-Methoxyamphetamine
The metabolism of 4-Methoxyamphetamine can be increased when combined with Canakinumab.
5-methoxy-N,N-dimethyltryptamine
The metabolism of 5-methoxy-N,N-dimethyltryptamine can be increased when combined with Canakinumab.
6-O-benzylguanine
The metabolism of 6-O-benzylguanine can be increased when combined with Canakinumab.
8-azaguanine
The metabolism of 8-azaguanine can be increased when combined with Canakinumab.
8-chlorotheophylline
The metabolism of 8-chlorotheophylline can be increased when combined with Canakinumab.
9-(N-methyl-L-isoleucine)-cyclosporin A
The risk or severity of adverse effects can be increased when Canakinumab is combined with 9-(N-methyl-L-isoleucine)-cyclosporin A.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be increased when combined with Canakinumab.
9-Deazaguanine
The metabolism of 9-Deazaguanine can be increased when combined with Canakinumab.
9-Methylguanine
The metabolism of 9-Methylguanine can be increased when combined with Canakinumab.
Abatacept
The risk or severity of adverse effects can be increased when Abatacept is combined with Canakinumab.
Abciximab
The risk or severity of adverse effects can be increased when Abciximab is combined with Canakinumab.
Abetimus
The risk or severity of adverse effects can be increased when Canakinumab is combined with Abetimus.
Abituzumab
The risk or severity of adverse effects can be increased when Canakinumab is combined with Abituzumab.
Abrilumab
The risk or severity of adverse effects can be increased when Canakinumab is combined with Abrilumab.
Acebutolol
The metabolism of Acebutolol can be increased when combined with Canakinumab.
Acefylline
The metabolism of Acefylline can be increased when combined with Canakinumab.
2 References
  1. 1 . 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: 19169963
  2. 2 . 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. doi: 10.1056/NEJMoa0810787.PubMed: 19494217