Mechanism of effect
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).
Pharmacodynamic
Canakinumab is and fully human mAb that neutralizes the bioactivity of human IL-1beta, which is involved in several inflammatory disorders.
Pharmacokinetics
Bioavailability: 66%
Peak plasma time: 2-7 days (children); 7 days (adults)
Peak plasma concentration: 16 +/- 3.5 mcg/mL
Vd: 6 L
Half-life: 26 days
Drug indications
Juvenile Arthritis , Cryopyrin-Associated Periodic Syndrome , Tumor Necrosis Factor Receptor-Associated Periodic Syndrome , Hyperimmunoglobulin D Syndrome , Mevalonate Kinase DeficiencyDosage
Adult
Cryopyrin-Associated Periodic Syndrome
>40 kg: 150 mg SC q8wk
15-40 kg: 2 mg/kg SC q8wk; may increase to 3 mg/kg if inadequate response
Tumor Necrosis Factor Receptor-Associated Periodic Syndrome
150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate
Hyperimmunoglobulin D Syndrome/Mevalonate Kinase Deficiency
150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate
Familial Mediterranean Fever
150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate
Pediatric
Cryopyrin-Associated Periodic Syndrome
<4 years
- Safety and efficacy not established
≥4 Years
- 15-40 kg: 2 mg/kg SC q8wk
- ≥40 kg: 150 mg SC q8wk
Tumor Necrosis Factor Receptor-Associated Periodic Syndrome
≤40 kg: 2 mg/kg SC q4wk; may increase to 4 mg/kg q4wk if the clinical response is not adequate
>40 kg: 150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate
Hyperimmunoglobulin D Syndrome/Mevalonate Kinase Deficiency
≤40 kg: 2 mg/kg SC q4wk; may increase to 4 mg/kg q4wk if the clinical response is not adequate
>40 kg: 150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate
Familial Mediterranean Fever
≤40 kg: 2 mg/kg SC q4wk; may increase to 4 mg/kg q4wk if the clinical response is not adequate
>40 kg: 150 mg SC q4wk; may increase to 300 mg q4wk if the clinical response is not adequate
Systemic Juvenile Idiopathic Arthritis
Indicated for active SJIA
<2 years: Safety and efficacy not established
≥2 years and weight ≥7.5 kg: 4 mg/kg SC qMonth; not to exceed 300 mg/doseSide effects
flu , Diarrhea , Headache , Proteinuria , nausea , vertigo , Hypocalcemia , Increased ALT , Hyperbilirubinemia , Weight increase , rhinitis , Decreased creatinine clearanceInteractions
Thymoglubin , Varicella-Zoster Vaccines , Golimumab , Hib vaccine , Azathioprine , Anti-thymocyte , Everolimus , Infliximab , Pneumovax , Tacrolimus , rotavirus vaccine , Japanese Encephalitis Virus Vaccine , Hepatitis B Vaccine , Temsirolimus , meningococcal polysaccharide vaccine , Anthrax vaccine , Polio vaccine, inactivated , Typhoid vaccine (live), oral , Anakinra , Baricitinib , Muromonab-CD3 , DIPHTHERIA & TETANUS TOXOID (Td ) , Ustekinumab , Rilonacept , Adalimumab , Measles vaccine , Rubella Vaccines , Tocilizumab , Basiliximab , Alefacept , Sirolimus , Cyclosporine , Glatiramer acetate , Mycophenolate mofetil , Hydroxychloroquine , Human papillomma virus vaccine , Meningococcal conjugate vaccine , Rabies Vaccine , RESLIZUMAB , alirocumabAlerts
Concomitant use of TNF-alpha or IL-1 antagonists
Risk of infections, reactivation of latent hepatitis/TB; interrupt if serious infection develops
Increase risk of lymphoma
May impair defenses against malignancies
MWS: increase risk of vertigo
Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop with rheumatic conditions, particularly SJIA; based on clinical trials, canakinumab did not increase incidence of MAS
Infections, predominantly of upper respiratory tract, in some instances serious, reported in isolated cases of unusual or opportunistic infections including aspergillosis, atypical mycobacterial infections, cytomegalovirus, herpes zoster; causal relationship of therapy to infections cannot be excluded
Points of recommendation
Tell your doctor if you have any changes in weight. Canakinumab doses are based on weight (especially in children and teenagers), and any changes may affect the dose.
Canakinumab can weaken your immune system. Your blood may need to be tested often.
Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.
Do not receive a "live" vaccine while using canakinumab. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.
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