canakinumab

Action and Spectrum

Actions and Spectrum: 

Action: 

Inhibition of IL-1β: canakinumab specifically binds to IL-1β and prevents its interaction with its receptors. This inhibits the downstream signaling pathways triggered by IL-1β, thereby reducing the inflammatory response. 

Spectrum:  

Systemic Juvenile Idiopathic Arthritis (SJIA): canakinumab is approved for treating SJIA in patients aged 2 years and older. SJIA is a form of juvenile arthritis characterized by systemic inflammation, fever, and joint pain. 

Cryopyrin-Associated Periodic Syndromes (CAPS): canakinumab is indicated for the treatment of CAPS, which includes a group of rare genetic autoinflammatory disorders. These syndromes involve excessive production of IL-1β, leading to recurrent fever, rash, and joint inflammation. 

Familial Mediterranean Fever (FMF): canakinumab may be used in the treatment of FMF, an autosomal recessive disorder characterized by recurrent episodes of fever, abdominal pain, and inflammation of the serous membranes. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

WBC count ≤0.8x LLN (10.4%) 

Nasopharyngitis (34%) 

Diarrhea (20%) 

Influenza (17%) 

Rhinitis (17%) 

Headache (14%) 

Nausea (14%) 

Vertigo (9-14%) 

Gastroenteritis (11%) 

Pharyngitis (11%) 

Weight increase (11%) 

Bronchitis (11%) 

Musculoskeletal pain (11%) 

WBC count ≤0.8x LLN (10.4%) 

1-10% 

Increased AST/ALT (4.1%) 

ANC <1x 109/L (6%) 

Decreased platelets (6.3%) 

Injection site pain (9%)  

Frequency Not Defined 

Mild bilirubin elevation 

Black Box Warning

Black Box Warning:  

None

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity: The utilization of this medication is contraindicated in persons with a documented hypersensitivity or intense allergic response to canakinumab or any of its constituent elements. Manifestations of allergic reactions may comprise indications like skin rash, itchiness, respiratory distress, or swelling of the facial region, lips, tongue, or throat. 

Active Infection: Drug may suppress the immune system, increasing the risk of infections. Therefore, it is generally not recommended to use canakinumab in individuals with active severe infections. Treatment with canakinumab should be postponed until the infection has resolved. 

Tuberculosis: Drug may increase the risk of tuberculosis (TB) reactivation or worsening of TB infections. Therefore, it is generally contraindicated in individuals with active or untreated latent TB infection. Prior screening for TB may be necessary before initiating treatment with canakinumab. 

Live Vaccines: Drug may interfere with the effectiveness of live vaccines. It is generally recommended to avoid live vaccines during treatment with canakinumab. If vaccination is necessary, it should be administered prior to starting canakinumab or during a treatment-free interval. 

Pregnancy and Breastfeeding: The use of canakinumab during pregnancy or breastfeeding is not well established. It should be used during pregnancy only if the potential benefits outweigh the potential risks. Similarly, it is not known whether canakinumab is excreted in human milk, so caution should be exercised if used while breastfeeding. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

canakinumab is a monoclonal antibody drug that belongs to a class of medications called interleukin-1 beta (IL-1β) inhibitors. 

Pharmacodynamics:  

canakinumab specifically targets and inhibits the activity of interleukin-1 beta (IL-1β), which is a pro-inflammatory cytokine involved in the immune response. IL-1β is known to play a role in the development of inflammation, fever, and pain. By blocking the activity of IL-1β, canakinumab helps reduce inflammation and related symptoms.   

Pharmacokinetics: 

Absorption 

canakinumab is administered via subcutaneous injection. Following administration, the drug is absorbed into the bloodstream. As it is an antibody, its absorption directly into the systemic circulation allows it to exert its therapeutic effects. 

Distribution 

Once canakinumab enters the bloodstream, it distributes throughout the body. It can reach various tissues and organs where IL-1β may be present, thereby exerting its anti-inflammatory effects.  

Metabolism 

As a monoclonal antibody, canakinumab is a large protein molecule that is unlikely to undergo significant metabolism in the body. Monoclonal antibodies are generally not metabolized by typical metabolic pathways like small molecule drugs. Instead, they are cleared from the body through other mechanisms. 

Excretion and Elimination 

canakinumab and other monoclonal antibodies are primarily eliminated from the body through proteolytic degradation and clearance processes. The exact route and mechanism of canakinumab excretion have not been fully elucidated. However, it is known that monoclonal antibodies are cleared from the body over time, with the exact elimination half-life varying between individuals. 

Adminstartion

Administration:  

Subcutaneous Injection: For subcutaneous administration, canakinumab is usually available as a pre-filled syringe or pen device. The injection is given just under the skin in the fatty tissue of the thigh, abdomen, or upper arm. 

Rotate injection sites to different areas to avoid irritation or tissue damage. 

If self-administering at home, ensure proper disposal of needles and syringes in a sharps container. 

Intravenous Infusion: canakinumab can also be administered as an intravenous infusion, typically in a healthcare setting such as a clinic or hospital. The infusion is delivered slowly into a vein over a specified period. 

The infusion is prepared and administered by a healthcare professional. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: canakinumab 

Why do we use canakinumab?  

Cryopyrin-Associated Periodic Syndromes (CAPS): canakinumab is approved for the treatment of CAPS, which includes three rare autoinflammatory disorders: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, and Neonatal-Onset Multisystem Inflammatory Disease.  

Systemic Juvenile Idiopathic Arthritis (SJIA): Drug is used to treat SJIA in children aged 2 years and older. SJIA is a form of juvenile idiopathic arthritis characterized by systemic inflammation and arthritis. canakinumab helps reduce symptoms and inflammation associated with SJIA. 

Adult-Onset Still’s Disease (AOSD): The drug has shown effectiveness in treating AOSD, a rare inflammatory disorder primarily affecting adults. It helps alleviate symptoms such as fever, joint pain, rash, and systemic inflammation. 

Gouty Arthritis: Drug is being investigated as a potential treatment for acute gouty arthritis, a condition caused by the buildup of uric acid crystals in the joints. It has shown promise in reducing pain and inflammation associated with gout attacks. 

Atherosclerosis: Drug has demonstrated potential in reducing cardiovascular events in individuals with a history of heart attack and high levels of inflammation as measured by C-reactive protein (CRP). It is being studied as an adjunct therapy to prevent recurrent cardiovascular events.