HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ILARIS safely and effectively. See full prescribing information for ILARIS.
ILARIS (canakinumab) injection for subcutaneous use
Initial U.S. Approval: 2009
RECENT MAJOR CHANGES
Warnings and Precautions, Serious Infections (5.1) 10/2014
INDICATIONS AND USAGE
ILARIS is an interleukin-1β blocker indicated for the treatment of:
Cryopyrin-Associated Periodic Syndromes (CAPS), in adults and children 4 years of age and older including:
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Familial Cold Autoinflammatory Syndrome (FCAS) (1.1)
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Muckle-Wells Syndrome (MWS) (1.1)
Active Systemic Juvenile Idiopathic Arthritis (SJIA) in patients aged 2 years and older (1.2)
DOSAGE AND ADMINISTRATION
Cryopyrin-Associated Periodic Syndromes (CAPS)
150 mg for CAPS patients with body weight greater than 40 kg and 2 mg/kg for CAPS patients with body weight greater than or equal to 15 kg and less than or equal to 40 kg. For children 15 to 40 kg with an inadequate response, the dose can be increased to 3 mg/kg. Administer subcutaneously every 8 weeks. (2.2)
Systemic Juvenile Idiopathic Arthritis (SJIA)
4 mg/kg (with a maximum of 300 mg) for patients with a body weight greater than or equal to 7.5 kg. Administer subcutaneously every 4 weeks. (2.3)
DOSAGE FORMS AND STRENGTHS
Sterile, single-use, glass vial containing 180 mg of ILARIS as a lyophilized powder for reconstitution. (3)
CONTRAINDICATIONS
Confirmed hypersensitivity to the active substance or to any of the excipients. (4)
WARNINGS AND PRECAUTIONS
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Interleukin-1 blockade may interfere with immune response to infections. Treatment with medications that work through inhibition of IL-1 has been associated with an increased risk of serious infections. ILARIS has been associated with an increased incidence of serious infections. Physicians should exercise caution when administering ILARIS to patients with infections, a history of recurring infections or underlying conditions which may predispose them to infections. Discontinue treatment with ILARIS if a patient develops a serious infection. Do not administer ILARIS to patients during an active infection requiring medical intervention. (5.1)
5.4
Live vaccines should not be given concurrently with ILARIS. Prior to initiation of therapy with ILARIS, patients should receive all recommended vaccinations. ()
CAPS: The most common adverse reactions greater than 10% reported by patients with CAPS treated with ILARIS are nasopharyngitis, diarrhea, influenza, headache and nausea. (6)
SJIA: The most common adverse drug reactions greater than 10% reported by patients with SJIA treated with ILARIS are infections (nasopharyngitis and upper respiratory tract infections), abdominal pain and injection site reactions. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
DRUG INTERACTIONS
No formal drug interaction studies have been conducted with ILARIS. (7)
USE IN SPECIFIC POPULATIONS
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Pregnancy: No human data. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. (8.1)
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Nursing Mothers: Caution should be exercised when administered to a nursing woman. (8.3)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 10/2014
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Cryopyrin-Associated Periodic Syndromes (CAPS)
ILARIS (canakinumab) is an interleukin-1β blocker indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), in adults and children 4 years of age and older including:
-
Familial Cold Autoinflammatory Syndrome (FCAS)
-
Muckle-Wells Syndrome (MWS)
1.2 Systemic Juvenile Idiopathic Arthritis (SJIA)
ILARIS is indicated for the treatment of active Systemic Juvenile Idiopathic Arthritis (SJIA) in patients aged 2 years and older.
2 DOSAGE AND ADMINISTRATION
2.1 General Dosing Information
INJECTION FOR SUBCUTANEOUS USE ONLY.
2.2 Cryopyrin-Associated Periodic Syndromes (CAPS)
The recommended dose of ILARIS is 150 mg for CAPS patients with body weight greater than 40 kg. For CAPS patients with body weight greater than or equal to 15 kg and less than or equal to 40 kg, the recommended dose is 2 mg/kg. For children 15 to 40 kg with an inadequate response, the dose can be increased to 3 mg/kg.
ILARIS is administered every eight weeks as a single dose via subcutaneous injection.
2.3 Systemic Juvenile Idiopathic Arthritis (SJIA)
The recommended dose of ILARIS for SJIA patients with a body weight greater than or equal to 7.5 kg is 4 mg/kg (with a maximum of 300 mg) administered every 4 weeks via subcutaneous injection.
2.4 Four Steps for Preparation and Administration
STEP 1: Using aseptic technique, reconstitute each vial of ILARIS by slowly injecting 1 mL of preservative-free Sterile Water for Injection with a 1 mL syringe and an 18 gauge x 2” needle.
STEP 2: Swirl the vial slowly at an angle of about 45° for approximately 1 minute and allow to stand for 5 minutes. Do not shake. Then gently turn the vial upside down and back again ten times. Avoid touching the rubber stopper with your fingers.
STEP 3: Allow to stand for about 15 minutes at room temperature to obtain a clear solution. The reconstituted solution has a final concentration of 150 mg/mL. Do not shake. Do not use if particulate matter is present in the solution. Tap the side of the vial to remove any residual liquid from the stopper. The reconstituted solution should be essentially free from particulates, and clear to opalescent. The solution should be colorless or may have a slight brownish-yellow tint. If the solution has a distinctly brown discoloration it should not be used. If not used within 60 minutes of reconstitution, the solution should be stored in the refrigerator at 2°C to 8°C (36°F to 46°F) and used within 4 hours. Slight foaming of the product upon reconstitution is not unusual.
STEP 4: Using a sterile syringe and needle carefully withdraw the required volume depending on the dose to be administered (0.2 mL to 1 mL) and subcutaneously inject using a 27 gauge x 0.5” needle.
Injection into scar tissue should be avoided as this may result in insufficient exposure to ILARIS.
ILARIS 180 mg powder for solution for injection is supplied in a single-use vial. Any unused product or waste material should be disposed of in accordance with local requirements.
3 DOSAGE FORMS AND STRENGTHS
ILARIS is supplied as a 180 mg white lyophilized powder for solution for subcutaneous injection. Reconstitution with 1 mL of preservative-free Sterile Water for Injection is required prior to subcutaneous administration of the drug, resulting in a total volume of 1.2 mL reconstituted solution. The reconstituted ILARIS is a clear to slightly opalescent, colorless to a slight brownish yellow tint, essentially free from particulates, 150 mg/mL solution.
4 CONTRAINDICATIONS
Confirmed hypersensitivity to the active substance or to any of the excipients [see Warnings and Precautions (5.3) and Adverse Reactions (6.2)].
5 WARNINGS AND PRECAUTIONS
5.1 Serious Infections
ILARIS has been associated with an increased risk of serious infections. Physicians should exercise caution when administering ILARIS to patients with infections, a history of recurring infections or underlying conditions which may predispose them to infections. ILARIS should not be administered to patients during an active infection requiring medical intervention. Administration of ILARIS should be discontinued if a patient develops a serious infection.
Infections, predominantly of the upper respiratory tract, in some instances serious, have been reported with ILARIS. Generally, the observed infections responded to standard therapy. Isolated cases of unusual or opportunistic infections (e.g., aspergillosis, atypical mycobacterial infections, cytomegalovirus, herpes zoster) were reported during ILARIS treatment. A causal relationship of ILARIS to these events cannot be excluded. In clinical trials, ILARIS has not been administered concomitantly with tumor necrosis factor (TNF) inhibitors. An increased incidence of serious infections has been associated with administration of another IL-1 blocker in combination with TNF inhibitors. Coadministration of ILARIS with TNF inhibitors is not recommended because this may increase the risk of serious infections [see Drug Interactions (7.1)].
Drugs that affect the immune system by blocking TNF have been associated with an increased risk of new tuberculosis and reactivation of latent tuberculosis (TB). It is possible that use of IL-1 inhibitors such as ILARIS increases the risk of reactivation of tuberculosis or of opportunistic infections.
Prior to initiating immunomodulatory therapies, including ILARIS, patients should be eva luated for active and latent tuberculosis infection. Appropriate screening tests should be performed in all patients. ILARIS has not been studied in patients with a positive tuberculosis screen, and the safety of ILARIS in individuals with latent tuberculosis infection is unknown. Patients testing positive in tuberculosis screening should be treated according to standard medical practice prior to therapy with ILARIS. All patients should be instructed to seek medical advice if signs, symptoms, or high risk exposure suggestive of tuberculosis (e.g., persistent cough, weight loss, subfebrile temperature) appear during or after ILARIS therapy.
Healthcare providers should follow current CDC guidelines both to eva luate for and to treat possible latent tuberculosis infections before initiating therapy with ILARIS.
5.2 Immunosuppression
The impact of treatment with anti-interleukin-1 (IL-1) therapy on the development of malignancies is not known. However, treatment with immunosuppressants, including ILARIS, may result in an increase in the risk of malignancies.
5.3 Hypersensitivity
Hypersensitivity reactions have been reported with ILARIS therapy. During clinical trials, no anaphylactic reactions have been reported. It should be recognized that symptoms of the underlying disease being treated may be similar to symptoms of hypersensitivity. ILARIS should not be administered to any patients with known clinical hypersensitivity to ILARIS [see Contraindications (4) and Adverse Reactions (6.2)].
5.4 Immunizations
Live vaccines should not be given concurrently with ILARIS [see Drug Interactions (7.2)]. Since no data are available on either the efficacy or on the risks of secondary transmission of infection by live vaccines in patients receiving ILARIS, live vaccines should not be given concurrently with ILARIS. In addition, because ILARIS may interfere with normal immune response to new antigens, vaccinations may not be effective in patients receiving ILARIS. No data are available on the effectiveness of vaccinations with inactivated (killed) antigens in patients receiving ILARIS [see Drug Interactions (7.2)].
Because IL-1 blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with ILARIS, adult and pediatric patients receive all recommended vaccinations, as appropriate, including pneumococcal vaccine and inactivated influenza vaccine. (See current recommended immunization schedules at the website of the Centers for Disease Control, http://www.cdc.gov/vaccines/schedules/index.html).
5.5 Macrophage Activation Syndrome
Macrophage activation syndrome (MAS) is a known, life-threatening disorder that may develop in patients with rheumatic conditions, in particular SJIA, and should be aggressively treated. Physicians should be attentive to symptoms of infection or worsening of SJIA, as these are known triggers for MAS. Eleven cases of MAS were observed in 201 SJIA patients treated with canakinumab in clinical trials. Based on the clinical trial experience, ILARIS does not appear to increase the incidence of MAS in SJIA patients, but no definitive conclusion can be made.
6 ADVERSE REACTIONS
Three hundred ninety-five patients, including approximately 250 children (aged 2 to 17 years) have been treated with ILARIS in interventional trials in CAPS or SJIA. The most frequently reported adverse drug reactions were infections predominantly of the upper respiratory tract. The majority of the events were mild to moderate although serious infections were observed. The type and frequency of adverse drug reactions appeared to be consistent over time.
Opportunistic infections have also been reported in patients treated with ILARIS [see Warnings and Precautions (5.1)].
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Treatment of CAPS
The data described herein reflect exposure to ILARIS in 104 adult and pediatric CAPS patients, including 20 FCAS, 72 MWS, 10 MWS/NOMID (Neonatal Onset Multisystem Inflammatory Disorder) overlap, 1 non-FCAS non-MWS, and 1 misdiagnosed in placebo-controlled (35 patients) and uncontrolled trials. Sixty-two patients were exposed to ILARIS for at least 6 months, 56 for at least 1 year and 4 for at least 3 years. A total of 9 serious adverse reactions were reported for CAPS patients. Among these were vertigo (2 patients), infections (3 patients), including intra-abdominal abscess following appendectomy (1 patient). The most commonly reported adverse reactions associated with ILARIS treatment in the CAPS patients were nasopharyngitis, diarrhea, influenza, headache, and nausea. One patient discontinued treatment due to potential infection.
CAPS Study 1 investigated the safety of ILARIS in an 8-week, open-label period (Part 1), followed by a 24-week, randomized withdrawal period (Part 2), followed by a 16-week, open-label period (Part 3). All patients were treated with ILARIS 150 mg subcutaneously or 2 mg/kg if body weight was greater than or equal to 15 kg and less than or equal to 40 kg (see Table 1).
Since all CAPS patients received ILARIS in Part 1, there are no controlled data on adverse events (AEs). Data in Table 1 are for all AEs for all CAPS patients receiving canakinumab. In CAPS Study 1, no pattern was observed for any type or frequency of adverse events throughout the three study periods.
Vertigo
Vertigo has been reported in 9% to 14% of patients in CAPS studies, exclusively in MWS patients, and reported as a serious adverse event in two cases. All events resolved with continued treatment with ILARIS.
Injection Site Reactions
In CAPS Study 1, subcutaneous injection site reactions were observed in 9% of patients in Part 1 with mild tolerability reactions; in Part 2, one patient each (7%) had a mild or a moderate tolerability reaction and, in Part 3, one patient had a mild local tolerability reaction. No severe injection-site reactions were reported and none led to discontinuation of treatment.
Treatment of SJIA
A total of 201 SJIA patients aged 2 to less than 20 years have received ILARIS in clinical trials. The safety of ILARIS compared to placebo was investigated in two phase 3 studies [see Clinical Studies (14.2)]. Patients in SJIA Study 1 received a single dose of ILARIS 4 mg/kg (n=43) or placebo (n=41) via subcutaneous injection and were assessed at Day 15 for the efficacy endpoints and had a safety analysis up to Day 29. SJIA Study 2 was a two-part study with an open-label, single-arm active treatment period (Part I) followed by a randomized, double-blind, placebo-controlled, event-driven withdrawal design (Part II). Overall, 177 patients were enrolled into the study and received ILARIS 4 mg/kg (up to 300 mg maximum) in Part I, and 100 patients received ILARIS 4 mg/kg (up to 300 mg maximum) every 4 weeks or placebo in Part II. Adverse drug reactions listed in Table 2 showed higher rates than placebo from both trials. The adverse drug reactions associated with ILARIS treatment in SJIA patients were infections, abdominal pain, and injection site reactions. Serious infections (e.g., pneumonia, varicella, gastroenteritis, measles, sepsis, otitis media, sinusitis, adenovirus, lymph node abscess, pharyngitis) were observed in approximately 4% to 5% (0.02 to 0.17 per 100 patient-days) of patients receiving ILARIS in both studies.
Adverse reactions are listed according to MedDRA version 15.0 system organ class.
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