Ilaris

Anti-Rheumatic Monoclonal Antibodies
Interleukin-1 Beta (IL-1 Beta) Inhibitors

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Canakinumab injection solution should be essentially free from particulates, clear to opalescent, colorless to slightly brownish-yellow tint. If the solution has a distinctly brown discoloration, is highly opalescent or contains visible particles, do not use.

Health care providers should perform administration of canakinumab.
 
Subcutaneous injection:
Canakinumab solution has a concentration of 150 mg/mL. Do NOT shake.
Using a sterile 1-mL syringe and 18-gauge, 2-inch needle, carefully withdraw the required volume depending on the dose to be administered.
Subcutaneously inject using a 27-gauge, 0.5-inch needle. Avoid injection into scar tissue as this may result in insufficient exposure to canakinumab.
Discard any unused product; the vial is for single-use and does not contain any preservatives.

macrophage activation syndrome / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known

thrombocytopenia / Delayed / 0.6-16.3
neutropenia / Delayed / 6.0-15.9
leukopenia / Delayed / 6.4-6.4
hypertriglyceridemia / Delayed / 2.7-5.6
elevated hepatic enzymes / Delayed / 0-4.1
antibody formation / Delayed / 1.2-3.5
immunosuppression / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
palpitations / Early / Incidence not known
hypotension / Rapid / Incidence not known
hyperuricemia / Delayed / Incidence not known

diarrhea / Early / 20.0-20.0
influenza / Delayed / 17.0-17.0
rhinitis / Early / 5.3-17.0
abdominal pain / Early / 7.0-16.0
nausea / Early / 14.0-14.0
vertigo / Early / 9.0-14.0
headache / Early / 14.0-14.0
pharyngitis / Delayed / 3.0-11.0
weight gain / Delayed / 11.0-11.0
musculoskeletal pain / Early / 11.0-11.0
back pain / Delayed / 3.1-3.1
dizziness / Early / 1.6-1.6
infection / Delayed / 10.0
cough / Delayed / Incidence not known
sinusitis / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
rash / Early / Incidence not known

Ilaris

Rx

Human monoclonal antibody that inhibits interleukin-1 beta
Approved for active still's disease (including adult-onset still's disease and systemic juvenile idiopathic arthritis), tumor necrosis factor (TNF) receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin D syndrome (HIDS)/mevanolate kinase deficiency (MKD), familial Mediterranean fever (FMF), gout flares, and cryopyrin-associated periodic syndromes (CAPS) including familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS)
Increases risk of serious infections; evaluate for latent TB before use

150 mg subcutaneously every 8 weeks. The efficacy of canakinumab was evident in most patients during the pivotal clinical trial after only 1 dose; symptoms of Cryopyrin-Associated Periodic Syndromes (CAPS) diminished within 24 hours in responding patients. The median C-reactive protein (CRP) and serum amyloid A protein (SAA) concentrations fell to within the normal range. Most (81%) of patients who stopped receiving canakinumab experienced a disease flare; the median time until the disease flare was 100 days. All patients who continued therapy with canakinumab maintained normal CRP and SAA concentrations. Upon reinitiation canakinumab, patients who experienced a disease flare responded again. At the end of the 48-week trial, 30 of 31 patients had no or minimal disease activity, according to the physician's assessment.

2 mg/kg subcutaneously every 8 weeks. If response is inadequate in children in this weight range, may consider dose increase to 3 mg/kg subcutaneously every 8 weeks.

4 mg/kg (Maximum: 300 mg/dose) subcutaneously every 4 weeks.

4 mg/kg (Maximum: 300 mg/dose) subcutaneously every 4 weeks.

150 mg subcutaneously every 4 weeks. The dose can be increased to 300 mg subcutaneously every 4 weeks if the clinical response is not adequate. During clinical trials, canakinumab was superior to placebo in the proportion of patients who resolved their disease flare by Day 15 and had no new flare over the next 16 weeks of treatment.

2 mg/kg subcutaneously every 4 weeks. May increase to 4 mg/kg subcutaneously every 4 weeks if the clinical response is not adequate. During clinical trials, canakinumab was superior to placebo in the proportion of patients who resolved their disease flare by Day 15 and had no new flare over the next 16 weeks of treatment.

150 mg subcutaneously as a single dose. May repeat the dose after at least 12 weeks in persons who require further treatment.

Efficacy has not been established. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommendation against the use of canakinumab outside of clinical trials. Dosing regimens being evaluated include: 4 mg/kg and 8 mg/kg IV once for patients 40 kg or less; 300 mg and 600 mg IV once for patients more than 40 kg; 450 mg IV once for patients 40 to 59 kg; 600 mg IV once for patients 60 to 80 kg; 750 mg IV once for patients more than 80 kg. All doses are to be diluted in 250 mL of 5% dextrose and infused over 2 hours.

Efficacy has not been established. The National Institutes of Health (NIH) COVID-19 treatment guidelines recommendation against the use of canakinumab outside of clinical trials. A single 150 mg subcutaneous injection is being evaluated in a retrospective and prospective observational study.

†Indicates off-label use

No formal studies have been conducted in patients with hepatic impairment.

No formal studies have been conducted in patients with renal impairment.

Abatacept: (Major) Concomitant use of abatacept with biological DMARDs, such as canakinumab, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with canakinumab.
Anakinra: (Major) Concomitant use of anakinra with other drugs that also block interleukin (IL)-1, such as canakinumab, is not recommended; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Baricitinib: (Major) Concomitant use of baricitinib with biologic DMARDs, such as canakinumab, is not recommended because of the possibility of additive immunosuppression and increased infection risk.
Basiliximab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as basilixumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Brodalumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as brodalumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Chikungunya Vaccine, Live: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Guselkumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as guselkumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Intranasal Influenza Vaccine: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Ixekizumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as ixekizumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Live Vaccines: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Measles/Mumps/Rubella Vaccines, MMR: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Rilonacept: (Major) Concomitant use of canakinumab with other drugs that block interleukin (IL)-1, such as rilonacept, is not recommended; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Rotavirus Vaccine: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Sarilumab: (Major) Avoid using sarilumab with other biological DMARDs including interleukin-1 receptor antagonists such as canakinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secukinumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as secukinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Siltuximab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as siltuximab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Smallpox Vaccine, Vaccinia Vaccine: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Tildrakizumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as tildrakizumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tocilizumab: (Major) Avoid using tocilizumab with other biological DMARDs including interleukin-1 receptor antagonists such as canakinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic DMARDs, such as canakinumab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Tumor Necrosis Factor modifiers: (Major) Avoid concomitant administration of canakinumab with tumor necrosis factor (TNF) modifiers; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection. An increased incidence of serious infections and an increased risk of neutropenia have been associated with administration of another IL-1 blocker in combination with TNF inhibitors. Based upon the potential for similar interactions, concomitant administration of canakinumab and TNF inhibitors is not recommended.
Typhoid Vaccine: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Upadacitinib: (Major) Concomitant use of upadacitinib with biologic DMARDs, such as canakinumab, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Ustekinumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as ustekinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Varicella-Zoster Virus Vaccine, Live: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).
Warfarin: (Moderate) Closely monitor the INR and adjust warfarin dosage as appropriate based on response if coadministration of warfarin and canakinumab is necessary. Concurrent use may decrease warfarin exposure and reduce its efficacy. Canakinumab therapy may normalize the expression of CYP enzymes that are involved in the metabolism of warfarin which are often suppressed during chronic inflammation.
Yellow Fever Vaccine, Live: (Major) Do not administer live vaccines to a patient who is receiving canakinumab; other vaccination schedules should be complete as recommended prior to initiating canakinumab treatment. No data are available regarding the risk of secondary transmission of infection by live vaccines, and the efficacy and safety of live vaccines have not been established in patients receiving canakinumab. The immune response to vaccines or toxoids may be decreased, as canakinumab may interfere with normal immune response to new antigens. Limited data are available on the effectiveness of vaccination with inactivated antigens in patients receiving canakinumab. Because interleukin-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with canakinumab, adult and pediatric patients receive any recommended vaccination (including pneumococcal vaccine and inactivated influenza vaccines).

Ilaris Subcutaneous Inj Pwd F/Sol: 180mg
Ilaris Subcutaneous Inj Sol: 1mL, 150mg

CAPS
more than 40 kg: 150 mg/dose subcutaneously every 8 weeks.
40 kg or less: 3 mg/kg/dose subcutaneously every 8 weeks.
TRAPS, HIDS/MKD, FMF
more than 40 kg: 300 mg/dose subcutaneously every 4 weeks.
40 kg or less: 4 mg/kg/dose subcutaneously every 4 weeks.
GOUT
150 mg/dose subcutaneously every 12 weeks.

CAPS
more than 40 kg: 150 mg/dose subcutaneously every 8 weeks.
40 kg or less: 3 mg/kg/dose subcutaneously every 8 weeks.
TRAPS, HIDS/MKD, FMF
more than 40 kg: 300 mg/dose subcutaneously every 4 weeks.
40 kg or less: 4 mg/kg/dose subcutaneously every 4 weeks.
GOUT
150 mg/dose subcutaneously every 12 weeks.

CAPS
more than 40 kg: 150 mg/dose subcutaneously every 8 weeks.
15 to 40 kg: 3 mg/kg/dose subcutaneously every 8 weeks.
TRAPS, HIDS/MKD, FMF
more than 40 kg: 300 mg/dose subcutaneously every 4 weeks.
40 kg or less: 4 mg/kg/dose subcutaneously every 4 weeks.
SJIA
7.5 kg or more: 4 mg/kg/dose (Max: 300 mg/dose) subcutaneously every 4 weeks.
GOUT
Safety and efficacy have not been established.

CAPS
4 years and older and more than 40 kg: 150 mg/dose subcutaneously every 8 weeks.
4 years and older and 15 to 40 kg: 3 mg/kg/dose subcutaneously every 8 weeks.
Less than 4 years: Safety and efficacy have not been established.
TRAPS, HIDS/MKD, FMF
2 years and older and more than 40 kg: 300 mg/dose subcutaneously every 4 weeks.
2 years and older and 40 kg or less: 4 mg/kg/dose subcutaneously every 4 weeks.
Less than 2 years: Safety and efficacy have not been established.
SJIA
2 years and older and 7.5 kg or more: 4 mg/kg/dose (Max: 300 mg/dose) subcutaneously every 4 weeks.
Less than 2 years: Safety and efficacy have not been established.
GOUT
Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Canakinumab is a human monoclonal antibody against interleukin (IL)-1 beta. Binding of canakinumab to IL-1 beta blocks the interaction with IL-1 receptors. Excessive release of IL-1 beta drives inflammation in patients with cryopyrin-associated periodic syndromes (CAPS), which is a rare, genetic-based disease. Patients with the disease have mutations in the NLRP-3 (CIAS1) gene that encodes the protein cryopyrin. Cryopyrin binds with an intrinsic inhibitor and controls the activation of caspase-1. Caspase-1 cleaves pro-interleukin-1 beta and IL-18 into the biologically active forms. Patients with CAPS have increased caspase activity and thus, increased biologically active IL-1 beta.
 
Canakinumab has a disease-modifying effect through autocrine down-regulation of IL-1 beta production. IL-1 beta has been shown both in vivo and in vitro to stimulate its own production. Unbound IL-1 beta in the tissue stimulates production of C-reactive protein (CRP) and serum amyloid A protein (SAA), leading to an increased probability of a disease flare. Canakinumab binds to IL-1 beta and suppresses free IL-1 beta; this disrupts this feedback mechanism and hence reduces IL-1 production to a rate of that seen in healthy subjects. CRP and SAA were rapidly reduced and reductions were sustained through 24 weeks following canakinumab treatment in patients with gout flares.

Canakinumab is administered subcutaneously. Canakinumab binds to serum interleukin (IL)-1 beta. The volume of distribution at steady-state varied with body weight and was estimated to be 6.01 L in a typical patient with cryopyrin-associated periodic syndromes (CAPS) weighing 70 kg, 3.2 L in a patient weighing 33 kg with systemic juvenile idiopathic arthritis (SJIA), 6.34 L for a patient weighing 70 kg with periodic fever syndrome, and 7.9 L in a patient weighing 93 kg with gout flares. Clearance of the drug also varied according to body weight and was estimated to be 0.174 L/day in a typical 70 kg patient with CAPS, 0.11 L/day in an SJIA patient weighing 33 kg, and 0.17 L/day in a periodic fever syndrome patient weighing 70 kg. After repeated administration, there was no indication of accelerated clearance or time-dependent change. The expected accumulation ratio was 1.3-fold for CAPS patients and 1.6-fold for SJIA patients after 6 months of 150 mg canakinumab subcutaneously every 8 weeks and 4 mg/kg subcutaneously every 4 weeks, respectively. The expected accumulation ratio was 1.1-fold for patients with gout flares following 150 mg canakinumab subcutaneously every 12 weeks. The mean terminal half-life was 26 days in adults with CAPS receiving subcutaneous dosing. Canakinumab pharmacokinetics were similar between patients with SJIA and adult-onset Still's disease.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: various CYP isoenzymes
The formation of CYP450 enzymes is suppressed by increased levels of cytokines (e.g., IL-1) during chronic inflammation. Thus it is expected that for a molecule that binds to IL-1, such as canakinumab, the formation of CYP450 enzymes could be normalized. This is clinically relevant for CYP450 substrates with a narrow therapeutic index (NTI), where the dose is individually adjusted (e.g., warfarin). Upon initiation of canakinumab, in patients being treated with drugs with an NTI, therapeutic monitoring of the effect or drug concentration should be performed and the individual dose of the medicinal product may need to be adjusted as needed.

Canakinumab has been investigated as an intravenous infusion. Exposure parameters (such as AUC and Cmax) increased in proportion to dose over the dose range of 0.30 to 10 mg/kg given as intravenous infusion.

The peak serum canakinumab concentration (Cmax) of 16 +/- 3.5 mcg/mL occurred approximately 7 days after subcutaneous administration of a single, 150 mg dose in adult patients with cryopyrin-associated periodic syndromes (CAPS). The absolute bioavailability of subcutaneous canakinumab was estimated to be 66%. Exposure parameters (such as AUC and Cmax) increased in proportion to dose over the dose range of 150 to 300 mg as a subcutaneous injection.

No information is available regarding the presence of canakinumab in breast-milk or the effects on milk production. A small number of published case reports do not demonstrate an association between maternal canakinumab use during breast-feeding and adverse effects in a breast-fed infant. Excretion of the drug into mature breast milk is considered unlikely due to the drug's high molecular weight. Absorption is unlikely because canakinumab is a protein that will likely be destroyed in the infant's gastrointestinal tract. Because maternal antibodies are known to be present in colostrum, there is a potential of exposing a nursing infant to the drug during the first few days after birth. Thus, health care providers are advised to monitor nursing babies for signs of infection as well as other drug-associated adverse effects including nasopharyngitis, diarrhea, rhinitis, nausea, headache, bronchitis, and gastroenteritis. Consider the developmental and health benefits of breast-feeding, the mother's need for canakinumab therapy, and potential adverse effects of the drug or an inadequately treated condition on the breastfed infant.