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

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.