Canakinumab

Mechanism of Action

Recombinant, human monoclonal antibody that reduces inflammation by inhibiting to interleukin-1-beta and preventing its interaction with cell surface receptors;

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

Canakinumab is a prescription medication used to treat rare genetic auto-inflammatory diseases known as Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS). Canakinumab is also approved to treat active systemic juvenile idiopathic arthritis (JIA) in patients aged 2 years and older.

Canakinumab belongs to a group of drugs called interleukin-1 beta blockers, which block a protein responsible for inflammation.

This medication comes in an injectable form to be injected just under the skin by your doctor or healthcare provider every 8 weeks.

Common side effects of canakinumab include cold symptoms, diarrhea, runny nose, and headache.

If canakinumab is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Cryopyrin-associated Periodic Syndromes

Management of cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), in adults and children ≥4 years of age;1 2 3 designated an orphan drug by FDA for use in these conditions.3 4

Results in clinical remission, based on physician’s assessment of global disease activity, in a majority of patients with MWS or FCAS.1 2 Also results in decreases in mean concentrations of acute phase reactants (serum amyloid A [SAA] and C-reactive protein [CRP]).1 2

Absorption

Bioavailability

Absolute bioavailability following sub-Q injection approximately 70%.1 Peak plasma concentrations achieved in approximately 7 days in adults and approximately 2–7 days in pediatric patients with CAPS.1

AUC and peak plasma concentrations increase in proportion to dose over a sub-Q dosage range of 150–300 mg.1

Onset

Improvement in symptom scores and objective markers of inflammation occurs within approximately 1 week following initiation of therapy in most patients.1

Distribution

Extent

Not known whether canakinumab is distributed into milk.1

Elimination

Half-life

Terminal half-life approximately 26 days in adults with CAPS.1

Terminal half-life approximately 23–26 days in pediatric patients.1

Special Populations

Pharmacokinetic data not available for patients with hepatic or renal impairment.1

No gender- or age-related differences in pharmacokinetics observed after correction for body weight.1

• If you have an allergy to canakinumab or any other part of canakinumab.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Hepatitis B, hepatitis C, HIV, or any other infection.
• If you are taking any of these drugs: Adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rilonacept, tocilizumab, or tofacitinib.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take canakinumab with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use canakinumab as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Irritation where the shot is given.
• Headache.
• Belly pain.
• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Muscle pain.
• Weight gain.
• Sore throat.
• Runny nose.
• Flu-like signs.
• Signs of a common cold.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous:

Ilaris: 150 mg/mL (1 mL) [contains polysorbate 80]

Solution Reconstituted, Subcutaneous [preservative free]:

Ilaris (150mg Delivered): 180 mg (1 ea) [contains polysorbate 80]

Hypersensitivity to canakinumab or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Active, severe infections

Refer to adult dosing.

Cryopyrin-associated periodic syndromes (CAPS): SubQ:

Children ≥4 years and Adolescents:

15 to 40 kg: 2 mg/kg every 8 weeks; may increase to 3 mg/kg if response inadequate; in clinical trials, dosage adjustments up to 8 mg/kg and/or increased dosing frequency were allowed for residual symptoms (Kuemmerle-Deschner 2011). For inadequate response, a dose titration schedule of 2 mg/kg every 7 days up to a maximum dose of 8mg/kg has been recommended (Ilaris Canadian product labeling 2017)

>40 kg: Refer to adult dosing

Familial Mediterranean Fever (FMF), Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD), Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS): SubQ: Children and Adolescents: Refer to adult dosing.

Systemic juvenile idiopathic arthritis (SJIA): SubQ: Children ≥2 years and ≥7.5 kg and Adolescents: 4 mg/kg every 4 weeks (maximum: 300 mg per dose)

Powder: Reconstitute each vial by slowly injecting SWFI 1 mL. Swirl vial slowly at a 45-degree angle for ~1 minute (do not shake), then allow solution to sit for 5 minutes. Gently turn vial (without touching rubber stopper) upside down and back 10 times. Allow to sit at room temperature for ~15 minutes. Do not shake. Solution may have a slight brownish-yellow tint; do not use if distinctly brown in color or if particulate matter is present in the solution. Slight foaming upon reconstitution is not unusual. Each reconstituted vial results in a final concentration of 150 mg/mL.

Applies to canakinumab: subcutaneous powder for injection, subcutaneous solution

Gastrointestinal

Very common (10% or more): Diarrhea (20%), nausea (14%), gastroenteritis, tonsillitis, upper abdominal pain, gastroesophageal reflux disease[Ref]

Genitourinary

Very common (10% or more): Urinary tract infection[Ref]

Hematologic

Very common (10% or more): Leukopenia
Frequency not reported: Hemoglobin increased, decreased white blood cells, decreased neutrophils, decreased platelets[Ref]

Hepatic

Rare (less than 0.1%): Elevated transaminases
Frequency not reported: Elevated serum bilirubin[Ref]

Hypersensitivity

Frequency not reported: Hypersensitivity reactions (unspecified)[Ref]

Immunologic

Very common (10% or more): Influenza (17%), viral infection (13%)[Ref]

Local

Very common (10% or more): Injection site reaction[Ref]

Musculoskeletal

Very common (10% or more): Musculoskeletal pain (11%), arthralgia
Common (1% to 10%): Back pain[Ref]

Nervous system

Very common (10% or more): Headache (14%), dizziness/vertigo (11%)[Ref]

Other

Very common (10% or more): Ear infection
Common (1% to 10%): Fatigue/asthenia[Ref]

Respiratory

Very common (10% or more): Nasopharyngitis (34%), rhinitis (17%), bronchitis (11%), pneumonia, sinusitis, rhinitis, pharyngitis, upper respiratory tract infection[Ref]

Dermatologic

Very common (10% or more): Cellulitis[Ref]

Metabolic

Very common (10% or more): Weight gain (11%)[Ref]

Renal

Very common (10% or more): Creatinine clearance decreased, proteinuria[Ref]

Some side effects of canakinumab may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

40 kg or less: The manufacturer product information should be consulted.
Greater than 40 kg: 150 mg subcutaneously every 8 weeks

Use: Cryopyrin-associated periodic syndromes (CAPS) including familial cold autoinflammatory syndrome (FCAS) and muckle-wells syndrome (MWS)

40 kg or less: The manufacturer product information should be consulted.

Greater than 40 kg: 150 mg subcutaneously every 4 weeks
-If the response is inadequate: Can increase to 300 mg subcutaneously every 4 weeks

Use: Autoinflammatory periodic fever syndromes including periodic tumor necrosis factor receptor associated periodic syndrome (TRAPS), hyperimmunoglobulin d syndrome/mevalonate kinase deficiency (MKD), and familial mediterranean fever (FMF)

4 years and older:
15 to 40 kg: 2 mg/kg subcutaneously every 8 weeks
-If the response is inadequate: Can increase to 3 mg/kg subcutaneously every 8 weeks

Greater than 40 kg: 150 mg subcutaneously every 8 weeks

Use: For the treatment of CAPS including FCAS and MWS

2 years and older:
40 kg or less: 2 mg/kg subcutaneously every 4 weeks
-If the response is inadequate: Can Increase to 4 mg/kg subcutaneously every 4 weeks

Greater than 40 kg: 150 mg subcutaneously every 4 weeks
-If the response is inadequate: Can increase to 300 mg subcutaneously every 4 weeks

Use: For the treatment of autoinflammatory periodic fever syndromes including TRAPS, HIDS/MKD, and FMF

Data not available