Presentation and Status in Health Basket
Solution for Injection: 1 X 150 mg
For CAPS, TRAPS, HIDS/MKD, FMF and SJIA, the treatment should be initiated and supervised by a specialist physician experienced in the diagnosis and treatment of the relevant indication. For gouty arthritis, the physician should be experienced in the use of biologics and Canakinumab should be administered by a healthcare professional. After proper training in the correct injection technique, patients or their caregivers may inject Canakinumab if the physician determines that it is appropriate and with medical follow-up as necessary.
CAPS: Adults, adolescents and children aged 2 years and older: The recommended starting dose of Canakinumab for CAPS patients is:
Adults, adolescents and children ≥ 4 years of age: 150 mg for patients with body weight >40 kg. 2 mg/kg for patients with body weight ≥15 kg and ≤40 kg. 4 mg/kg for patients with body weight ≥7.5 kg and <15 kg
Children 2 to <4 years of age: 4 mg/kg for patients with body weight ≥7.5 kg. This is administered every eight weeks as a single dose via subcutaneous injection.
For patients with a starting dose of 150 mg or 2 mg/kg, if a satisfactory clinical response (resolution of rash and other generalised inflammatory symptoms) has not been achieved 7 days after treatment start, a second dose of Canakinumab at 150 mg or 2 mg/kg can be considered. If a full treatment response is subsequently achieved, the intensified dosing regimen of 300 mg or 4 mg/kg every 8 weeks should be maintained. If a satisfactory clinical response has not been achieved 7 days after this increased dose, a third dose of Canakinumab at 300 mg or 4 mg/kg can be considered. If a full treatment response is subsequently achieved, maintaining the intensified dosing regimen of 600 mg or 8 mg/kg every 8 weeks should be considered, based on individual clinical judgement. For patients with a starting dose of 4 mg/kg, if a satisfactory clinical response has not been achieved 7 days after treatment start, a second dose of Canakinumab 4 mg/kg can be considered. If a full treatment response is subsequently achieved, maintaining the intensified dosing regimen of 8 mg/kg every 8 weeks should be considered, based on individual clinical judgement.
TRAPS, HIDS/MKD and FMF: Adults, adolescents and children aged 2 years and older: The recommended starting dose of Canakinumab in TRAPS, HIDS/MKD and FMF patients is: 150 mg for patients with body weight > 40 kg. 2 mg/kg for patients with body weight ≥ 7.5 kg and ≤ 40 kg. This is administered every four weeks as a single dose via subcutaneous injection. If a satisfactory clinical response has not been achieved 7 days after treatment start, a second dose of Canakinumab at 150 mg or 2 mg/kg can be considered. If a full treatment response is subsequently achieved, the intensified dosing regimen of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) every 4 weeks should be maintained. Continued treatment with Canakinumab in patients without clinical improvement should be reconsidered by the treating physician.
SJIA: The recommended dose of Canakinumab for SJIA patients with body weight ≥ 7.5 kg is 4 mg/kg (up to a maximum of 300 mg) administered every four weeks via subcutaneous injection. Continued treatment with Canakinumab in patients without clinical improvement should be reconsidered by the treating physician.
Gouty arthritis: Management of hyperuricaemia with appropriate urate lowering therapy (ULT) should be instituted or optimised. Canakinumab should be used as an on-demand therapy to treat gouty arthritis attacks. The recommended dose of Canakinumab for adult patients with gouty arthritis is 150 mg administered subcutaneously as a single dose during an attack. For maximum effect, Canakinumab should be administered as soon as possible after the onset of a gouty arthritis attack. Patients who do not respond to initial treatment should not be re-treated with Canakinumab. In patients who respond and require re-treatment, there should be an interval of at least 12 weeks before a new dose of Canakinumab may be administered.
CAPS, TRAPS, HIDS/MKD and FMF: The safety and efficacy of Ilaris in CAPS, TRAPS, HIDS/MKD and FMF patients under 2 years of age have not been established. Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.
SJIA: The safety and efficacy of Ilaris in SJIA patients under 2 years of age have not been established. No recommendation on a posology can be made.
Gouty arthritis: There is no relevant use of Ilaris in the paediatric population in the indication gouty arthritis.
Elderly: No dose adjustment is required.
Hepatic impairment: Ilaris has not been studied in patients with hepatic impairment.
Renal impairment: No dose adjustment is needed in patients with renal impairment. However, clinical experience in such patients is limited.
Method of administration: For subcutaneous use. The following are suitable injection sites: upper thigh, abdomen, upper arm or buttocks. It is recommended to select a different injection site each time the product is injected to avoid soreness. Broken skin and areas which are bruised or covered by a rash should be avoided. Injection into scar tissue should be avoided as this may result in insufficient exposure to Ilaris.
Each vial of Ilaris is for a single use in a single patient, for a single dose.
Periodic Fever Syndromes: Canakinumab is indicated for the treatment of the following autoinflammatory periodic fever syndromes in adults, adolescents and children aged 2 years and older:
Cryopyrin-Associated Periodic Syndromes (CAPS): Canakinumab is indicated for the treatment of cryopyrin-associated periodic syndromes (CAPS) in adults, adolescents and children aged 2 years and older with body weight of 7.5 kg or above, including: Muckle-wells syndrome (MWS). Neonatal-onset multisystem inflammatory disease (NOMID) / chronic infantile. neurological, cutaneous, articular syndrome (CINCA). Severe forms of familial cold autoinflammatory syndrome (FCAS) / familial cold. urticaria (FCU) presenting with signs and symptoms beyond cold-induced urticarial skin rash.
Indicated for Tumour necrosis factor (TNF) receptor associated periodic syndrome (TRAPS).
Indicated for the treatment of hyperimmunoglobulin D syndrome (HIDS)/ mevalonate kinase deficiency (MKD).
Familial Mediterranean fever (FMF): Canakinumab is indicated for the treatment of familial Mediterranean fever (FMF) in patients in whom colchicine is contraindicated, is not tolerated, or does not provide an adequate response despite the highest tolerable dose of colchicine. Canakinumab can be given as monotherapy or in combination with colchicine.
Canakinumab is also indicated for the treatment of:
Systemic Juvenile Idiopathic Arthritis (SJIA): in patients aged 4 years and older.
Gouty arthritis: Canakinumab is indicated for the symptomatic treatment of adult patients with frequent gouty arthritis attacks (at least 3 attacks in the previous 12 months) in whom non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine are contraindicated, are not tolerated, or do not provide an adequate response, and in whom repeated courses of corticosteroids are not appropriate.
Hypersensitivity to the active substance or to any of the excipients. Active, severe infections.
Infections: Canakinumabs is associated with an increased incidence of serious infections. Therefore patients should be monitored carefully for signs and symptoms of infections during and after treatment with Canakinumabs. Physicians should exercise caution when administering Canakinumabs to patients with infections, a history of recurring infections or underlying conditions which may predispose them to infections.
Treatment of CAPS, TRAPS, HIDS/MKD, FMF and SJIA: Canakinumabs should not be initiated or continued in patients during an active infection requiring medical intervention.
Treatment of gouty arthritis: Canakinumabs should not be administered during an active infection. Concomitant use of Canakinumabs with tumour necrosis factor (TNF) inhibitors is not recommended because this may increase the risk of serious infections. Isolated cases of unusual or opportunistic infections (including aspergillosis, atypical mycobacterial infections, herpes zoster) have been reported during Canakinumabs treatment. The causal relationship of Canakinumabs to these events cannot be excluded.
Neutropenia and leukopenia: Neutropenia (absolute neutrophil count [ANC] < 1.5 x 109/l) and leukopenia have been observed with medicinal products that inhibit IL-1, including Canakinumabs. . Treatment with Canakinumabs should not be initiated in patients with neutropenia or leukopenia. It is recommended that white blood cell (WBC) counts including neutrophil counts be assessed prior to initiating treatment and again after 1 to 2 months. For chronic or repeated therapies, it is also recommended to assess WBC counts periodically during treatment. If a patient becomes neutropenic or leukopenic, the WBC counts should be monitored closely and treatment discontinuation should be considered.
Malignancies: Malignancy events have been reported in patients treated with Canakinumabs. The risk for the development of malignancies with anti-interleukin (IL)-1 therapy is unknown.
Hypersensitivity reactions: Hypersensitivity reactions with Canakinumabs therapy have been reported. The majority of these events were mild in severity. During clinical development of Canakinumabs in over 2,600 patients, no anaphylactoid or anaphylactic reactions were reported. However, the risk of severe hypersensitivity reactions, which is not uncommon for injectable proteins, cannot be excluded.
Hepatic function: Transient and asymptomatic cases of elevations of serum transaminases or bilirubin have been reported in clinical trials.
Vaccinations: No data are available on the risk of secondary transmission of infection by live (attenuated) vaccines in patients receiving Ilaris. Therefore, live vaccines should not be given concurrently with Ilaris unless the benefits clearly outweigh the risks. Prior to initiation of Ilaris therapy it is recommended that adult and paediatric patients receive all vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza vaccine.
Mutation in NLRP3 gene in CAPS patients: Clinical experience in CAPS patients without a confirmed mutation in the NLRP3 gene is limited.
Macrophage activation syndrome in SJIA patients: Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in patients with rheumatic conditions, in particular SJIA. If MAS occurs, or is suspected, evaluation and treatment should be started as early as possible. Physicians should be attentive to symptoms of infection or worsening of SJIA, as these are known triggers for MAS. Based on clinical trial experience, Canakinumabs does not appear to increase the incidence of MAS in SJIA patients, but no definitive conclusion can be made.
See prescribing information for full details.
Infections and infestations: Very common: Respiratory tract infections (including pneumonia, bronchitis, influenza, viral infection, sinusitis, rhinitis, pharyngitis, tonsillitis, nasopharyngitis, upper respiratory tract infection), Ear infection, Cellulitis, Gastroenteritis, Urinary tract infection. Common: Vulvovaginal candidiasis.
Nervous system disorders: Common: Dizziness/vertigo.
Gastrointestinal disorders: Very common: Upper abdominal pain.
Skin and subcutaneous tissue disorders: Very common: Injection site reaction.
Musculoskeletal and connective tissue disorders: Very common: Arthralgia. Common: Musculoskeletal pain, Back pain.
General disorders and administration site conditions: Common: Fatigue/asthenia.
Investigations: Very common: Creatinine renal clearance decreased, Proteinuria, Leukopenia. Common: Neutropenia.
See prescribing information for full details.
Interactions between Canakinumab and other medicinal products have not been investigated in formal studies. An increased incidence of serious infections has been associated with administration of another IL-1 blocker in combination with TNF inhibitors. Use of Canakinumab with TNF inhibitors is not recommended because this may increase the risk of serious infections. The expression of hepatic CYP450 enzymes may be suppressed by the cytokines that stimulate chronic. inflammation, such as interleukin-1 beta (IL-1 beta). Thus, CYP450 expression may be reversed when potent cytokine inhibitory therapy, such as canakinumab, is introduced. This is clinically relevant for CYP450 substrates with a narrow therapeutic index where the dose is individually adjusted. On initiation of canakinumab in patients being treated with this type of medicinal product, therapeutic monitoring of the effect or of the active substance concentration should be performed and the individual dose of the medicinal product adjusted as necessary. No data are available on either the effects of live vaccination or the secondary transmission of infection by live vaccines in patients receiving Canakinumab. Therefore, live vaccines should not be given concurrently with Canakinumab unless the benefits clearly outweigh the risks. Should vaccination with live vaccines be indicated after initiation of Canakinumab treatment, the recommendation is to wait for at least 3 months after the last Canakinumab injection and before the next one. The results of a study in healthy adult subjects demonstrated that a single dose of Canakinumab 300 mg did not affect the induction and persistence of antibody responses after vaccination with influenza or glycosylated protein based meningococcus vaccines. The results of a 56-week, open label study in CAPS patients aged 4 years and younger demonstrated that all patients who received non-live, standard of care childhood vaccinations developed protective antibody levels.
Pregnancy and Lactation
Pregnancy: There is a limited amount of data from the use of canakinumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. The risk for the fetus/mother is unknown. Women who are pregnant or who desire to become pregnant should therefore only be treated after a thorough benefit-risk evaluation.
Lactation: It is unknown whether canakinumab is excreted in human milk. The decision whether to breast-feed during Canakinumabs therapy should therefore only be taken after a thorough benefit-risk evaluation.
See prescribing information for full details.
Reported experience with overdose is limited. In early clinical trials, patients and healthy volunteers received doses as high as 10 mg/kg administered intravenously or subcutaneously without evidence of acute toxicity. In case of overdose, it is recommended for the patient to be monitored for any signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted immediately.
Compatibility: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Storage: Store in a refrigerator (2°C – 8°C). Do not freeze. Store in the original package in order to protect from light. After reconstitution, from a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C – 8°C.