Ilaris

Generic Name: Canakinumab
Class: Other Miscellaneous Therapeutic Agents
Chemical Name: Immunoglobulin G1, anti-(human interleukin 1β) (human clone ACZ885 heavy chain V region)
Molecular Formula: C₆₄₅₂H₉₉₅₈N₁₇₂₂O₂₀₁₀S₄₂
CAS Number: 91613-48-2

Introduction

Interleukin-1 beta (IL-1β) blocker; a recombinant human anti-human IL-1β monoclonal antibody.^{1 2 3}

Uses for Ilaris

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}

Ilaris Dosage and Administration

Administration

Sub-Q Administration

Administer by sub-Q injection.¹

Injections should be performed by a clinician; the drug is not intended for self-administration.^{1 5}

Do not inject into scar tissue; this may result in insufficient exposure to the drug.¹ Do not inject into areas where skin is already swollen or erythematous.¹

Reconstitution

Reconstitute canakinumab lyophilized powder for injection by slowly adding 1 mL of preservative-free sterile water for injection (using a 1-mL syringe with an 18-gauge, 2-inch needle) to a vial containing 180 mg of canakinumab to provide a solution containing 150 mg/mL.¹

Slowly swirl vial at an angle of about 45° for approximately one minute. Allow to stand for 5 minutes and then gently invert vial 10 times; slight foaming may occur.¹ Do not touch rubber stopper or shake vial.¹ Allow reconstituted solution to stand at room temperature for approximately 15 minutes to obtain a clear solution.¹ Tap the side of the vial to remove any residual liquid from the stopper.¹ The reconstituted solution should be clear to opalescent, colorless to slightly brownish-yellow, and essentially free from particulates.¹

Before administration, withdraw the appropriate dose into a syringe using a 27-gauge, ½-inch needle.¹ Discard unused portions of the reconstituted solution; the solution contains no preservatives.¹

Dosage

Pediatric Patients

Cryopyrin-associated Periodic Syndromes

Sub-Q

Children ≥4 years of age who weigh >40 kg: 150 mg once every 8 weeks.¹

Children ≥4 years of age who weigh 15–40 kg: 2 mg/kg once every 8 weeks.¹ In patients with inadequate response, may increase dosage to 3 mg/kg once every 8 weeks.¹

Adults

Cryopyrin-associated Periodic Syndromes

Sub-Q

Adults who weigh >40 kg: 150 mg once every 8 weeks.¹

Adults who weigh 15–40 kg: 2 mg/kg once every 8 weeks.¹

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Ilaris

Contraindications

• No known contraindications.¹

Warnings/Precautions

Infectious Complications

IL-1 blockade may interfere with immune response to infections; possible increased risk of serious infections.^{1 2} Potentially serious infections, predominantly involving the upper respiratory tract, reported.¹ Unusual or opportunistic infections not reported during premarketing studies.¹

Do not initiate canakinumab in patients with an active infection requiring medical treatment or a chronic infection (e.g., HIV, HBV, or HCV infection); discontinue therapy if a serious infection occurs.¹ Use with caution in patients with infections, a history of recurring infections, or underlying conditions which may predispose them to infections.¹

May increase risk of tuberculosis or other atypical or opportunistic infections.¹ Evaluate patients for latent tuberculosis prior to initiation of canakinumab therapy.¹ Not studied in patients with latent tuberculosis infection; safety in such patients not known.¹ When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to canakinumab therapy.¹

Immunosuppression and Malignancies

Effect on the development of malignancies not known.¹ However, possible increased risk of malignancies in patients receiving immunosuppressive agents, including canakinumab.¹

Immunization

Avoid live vaccines during canakinumab therapy.¹ (See Vaccines under Interactions.)

Vaccine efficacy may be reduced.¹ Review vaccination status of all patients and administer all age-appropriate vaccines, including pneumococcal vaccine and influenza virus vaccine inactivated, prior to initiation of canakinumab therapy.¹

Immunologic Effects and Antibody Formation

Development of antibodies to canakinumab not reported to date.^{1 2 3}

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether canakinumab is distributed into milk.¹ Caution if used in nursing women.¹

Pediatric Use

Safety and efficacy not established in children <4 years of age.¹

Evaluated in 23 pediatric patients 4–17 years of age with CAPS; symptoms and objective markers of inflammation improved in most patients and overall efficacy and safety were similar to those observed in adults.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹

Hepatic Impairment

Pharmacokinetics not studied in patients with hepatic impairment.¹

Renal Impairment

Pharmacokinetics not studied in patients with renal impairment.¹

Common Adverse Effects

Nasopharyngitis, diarrhea, influenza, rhinitis, headache, nausea, bronchitis, gastroenteritis, musculoskeletal pain, pharyngitis, vertigo, weight gain, injection site reactions.¹

Interactions for Ilaris

No formal drug interaction studies to date.¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Because increased levels of cytokines (e.g., IL-1) during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of IL-1 activity by canakinumab may normalize formation of CYP enzymes.¹

Drugs metabolized by CYP isoenzymes that have a low therapeutic index: Monitor therapeutic effect and/or serum concentrations following initiation of canakinumab; adjust dosage of the CYP substrate as needed.¹

Vaccines

Data not available regarding efficacy of inactivated vaccines in patients receiving canakinumab.¹ (See Immunization under Cautions.)

Do not administer live vaccines to patients receiving canakinumab.¹ Data not available regarding efficacy of live vaccines or risk of secondary transmission of infection by live vaccines in patients receiving the drug.¹

Manufacturer makes no specific recommendations regarding the length of time to wait between discontinuance of canakinumab and administration of a live vaccine or the length of time to wait between administration of a live vaccine and initiation of canakinumab therapy.¹

Specific Drugs

Drug	Interaction	Comments
IL-1 blocking agents (e.g., anakinra, rilonacept)	Potential pharmacologic interaction1	Concomitant use not recommended1
TNF blocking agents (e.g., adalimumab, certolizumab, etanercept, golimumab, infliximab)	Potential for increased risk of serious infections and neutropenia1	Concomitant use not recommended1
Warfarin	Possible effect on warfarin metabolism (increased levels of IL-1 during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of IL-1 activity by canakinumab may normalize formation of CYP enzymes)1	Monitor therapeutic effect of warfarin; adjust warfarin dosage as needed1

Ilaris Pharmacokinetics

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

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original carton to protect from light.¹

Following reconstitution, store at room temperature, protect from light, and use within 60 minutes or store at 2–8°C and use within 4 hours.¹

Actions

• Recombinant human anti-human interleukin-1 beta (IL-1β) monoclonal antibody belonging to the IgG1/κ isotype subclass.^{1 3}

• Binds to IL-1β and neutralizes its activity by blocking its interaction with IL-1 receptors;^{1 2} does not bind interleukin-1 alpha (IL-1α) or interleukin-1 receptor antagonist (IL-1Ra).^{1 2 3} Mutations in the NLRP-3 gene in patients with CAPS result in an overactive inflammasome, which causes excessive release of activated IL-1β.¹

• Results in normalization of serum concentrations of SAA and CRP, indicators of inflammatory disease activity.¹ Elevated SAA concentrations have been associated with the development of systemic amyloidosis in patients with CAPS.¹

Advice to Patients

• Importance of providing a copy of the manufacturer’s patient information to all patients.^{1 5} Importance of discussing any questions pertaining to the manufacturer’s patient information.^{1 5}

• Risk of injection site reactions (e.g., pain, erythema, swelling, pruritus, bruising, mass, inflammation, dermatitis, edema, urticaria, vesicles, warmth, hemorrhage).¹ Importance of informing clinician of any persistent injection site reaction.¹

• Risk of serious infection.¹ Importance of informing clinicians immediately if any signs or symptoms of infection (e.g., fever, cough, redness in one part of the body, warmth or swelling of the skin) occur.^{1 5}

• Risk of vertigo.^{1 5}

• Importance of reviewing vaccination status with clinician and receiving all age-appropriate vaccines prior to initiation of canakinumab therapy.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., IL-1 antagonists, TNF-blocking agents, immunizations, corticosteroids) or OTC drugs, dietary supplements, and/or herbal products, as well as any concomitant illnesses (e.g., active or chronic infections).^{1 5}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 5}

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Canakinumab

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for subcutaneous use	180 mg	Ilaris (available in single-dose vials)	Novartis