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Drug Information on Ilaris - Novartis Pharmaceuticals Corporation | Pharmaguru.com
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Ilaris (Novartis Pharmaceuticals Corporation)
INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1 VIAL, SINGLE-USE in 1 CARTON (0078-0582-61) > 1 mL in 1 VIAL, SINGLE-USE Label Information
Complete Ilaris Information
ILARIS is an interleukin-1Î² blocker indicated for the treatment of:
1.1 Periodic Fever Syndromes 1.2 Systemic Juvenile Idiopathic Arthritis (SJIA)
2.1 General Dosing Information 2.2 Cryopyrin-Associated Periodic Syndromes (CAPS) 2.3 Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome/Mevalonate Kinase Deficiency (HIDS/MKD), and Familial Mediterranean Fever (FMF) 2.4 Systemic Juvenile Idiopathic Arthritis (SJIA) 2.5 Preparation and Administration of ILARIS Lyophilized Powder 2.6 Administration of ILARIS Solution
5.1 Serious Infections 5.2 Immunosuppression 5.3 Hypersensitivity 5.4 Immunizations 5.5 Macrophage Activation Syndrome
6.1 Clinical Trials Experience 6.2 Hypersensitivity 6.3 Immunogenicity 6.4 Laboratory Findings
7.1 TNF-Blocker and IL-1 Blocking Agent 7.2 Immunization 7.3 Cytochrome P450 Substrates
8.1 Pregnancy 8.2 Lactation 8.4 Pediatric Use 8.5 Geriatric Use 8.6 Patients with Renal Impairment 8.7 Patients with Hepatic Impairment
14.1 Treatment of CAPS 14.2 Treatment of Periodic Fever Syndromes: TRAPS, HIDS/MKD, and FMF 14.3 Treatment of SJIA
ILARIS® (canakinumab) is an interleukin-1Î² (IL-1 Î²) blocker indicated for the treatment of the following autoinflammatory Periodic Fever Syndromes:
STEP 1: Using aseptic technique, reconstitute each vial of ILARIS lyophilized powder by slowly injecting 1 mL of Sterile Water for Injection with a 1-mL syringe and an 18-gauge x 2â€ needle.
STEP 4: Using a sterile 1-mL syringe and needle, carefully withdraw the required volume depending on the dose to be administered and subcutaneously inject using a 27-gauge x 0.5â€ needle.
STEP 2: Using a sterile 1-mL syringe and 18-gauge x 2â€ needle, carefully withdraw the required volume depending on the dose to be administered and subcutaneously inject using a 27-gauge x 0.5â€ needle.
In embryo-fetal development studies, pregnant marmoset monkeys received canakinumab from gestation days 25 to 140 at doses that produced exposures approximately 11 times that achieved with MRHD and greater (on a plasma area under the curve (AUC) basis with maternal subcutaneous doses of 15, 50, or 150 mg/kg twice weekly). ILARIS did not elicit any evidence of embryotoxicity or fetal malformations. There were increases in the incidence of incomplete ossification of the terminal caudal vertebra and misaligned and/or bipartite vertebra in fetuses at all dose levels when compared to concurrent controls suggestive of delay in skeletal development in the marmoset. Since ILARIS does not cross-react with mouse or rat IL-1Î², pregnant mice were subcutaneously administered a murine analog of ILARIS at doses of 15, 50, or 150 mg/kg during the period of organogenesis on gestation days 6, 11, and 17. The incidence of incomplete ossification of the parietal and frontal skull bones of fetuses was increased in a dose-dependent manner at all dose levels tested.
There is no information regarding the presence of canakinumab in human milk, the effects on the breastfed infant, or the effects on milk production. Human IgG is known to be present in human milk. The effects of canakinumab in breast milk and possible systemic exposure in the breastfed infant are unknown. The developmental and health benefits of breastfeeding should be considered along with the motherâ€™s clinical need for ILARIS and any potential adverse effects on the breastfed infant from canakinumab or from the underlying maternal condition.
Canakinumab is a recombinant, human anti-human-IL-1Î² monoclonal antibody that belongs to the IgG1/Îº isotype subclass. It is expressed in a murine Sp2/0-Ag14 cell line and comprised of two 447- (or 448-) residue heavy chains and two 214-residue light chains, with a molecular mass of 145157 Daltons when deglycosylated. Both heavy chains of canakinumab contain oligosaccharide chains linked to the protein backbone at asparagine 298 (Asn 298).
The biological activity of canakinumab is measured by comparing its inhibition of IL-1Î²-dependent expression of the reporter gene luciferase to that of a canakinumab internal reference standard, using a stably transfected cell line.
Canakinumab is a human monoclonal anti-human IL-1Î² antibody of the IgG1/Îº isotype. Canakinumab binds to human IL-1Î² and neutralizes its activity by blocking its interaction with IL-1 receptors, but it does not bind IL-1Î± or IL-1 receptor antagonist (IL-1ra).
The NLRP-3 gene encodes the protein cryopyrin, an important component of the inflammasome. Cryopyrin regulates the protease caspase-1 and controls the activation of IL-1Î². Mutations in NLRP-3 result in an overactive inflammasome resulting in excessive release of activated IL-1Î² that drives inflammation. SJIA is a severe autoinflammatory disease, driven by innate immunity by means of proinflammatory cytokines such as IL-1Î².
Canakinumab binds to serum IL-1Î². Canakinumab volume of distribution (Vss) varied according to body weight and was estimated to be 6.01 liters in a typical CAPS patient weighing 70 kg, 3.2 liters in a SJIA patient weighing 33 kg, and 6.34 liters for a Periodic Fever Syndrome (TRAPS, HIDS/MKD, FMF) patient weighing 70 kg. The expected accumulation ratio was 1.3-fold for CAPS patients and 1.6-fold for SJIA patients following 6 months of subcutaneous dosing of 150 mg ILARIS every 8 weeks and 4 mg/kg every 4 weeks, respectively.
As canakinumab does not cross-react with rodent IL-1Î², male and female fertility was evaluated in a mouse model using a murine analog of canakinumab. Male mice were treated weekly beginning 4 weeks prior to mating and continuing through 3 weeks after mating. Female mice were treated weekly for 2 weeks prior to mating through gestation day 3 or 4. The murine analog of canakinumab did not alter either male or female fertility parameters at subcutaneous doses up to 150 mg/kg.
The efficacy and safety of ILARIS for the treatment of CAPS was demonstrated in CAPS Study 1, a 3-part trial in patients 9 to 74 years of age with the MWS phenotype of CAPS. Throughout the trial, patients weighing more than 40 kg received ILARIS 150 mg and patients weighing 15 to 40 kg received 2 mg/kg. Part 1 was an 8-week open-label, single-dose period where all patients received ILARIS. Patients who achieved a complete clinical response and did not relapse by Week 8 were randomized into Part 2, a 24-week randomized, double-blind, placebo-controlled withdrawal period. Patients who completed Part 2 or experienced a disease flare entered Part 3, a 16-week open-label active treatment phase. A complete response was defined as ratings of minimal or better for physicianâ€™s assessment of disease activity (PHY) and assessment of skin disease (SKD) and had serum levels of C-Reactive Protein (CRP) and Serum Amyloid A (SAA) less than 10 mg/L. A disease flare was defined as a CRP and/or SAA values greater than 30 mg/L and either a score of mild or worse for PHY or a score of minimal or worse for PHY and SKD.
Table 3: Physicianâ€™s Global Assessment of Auto Inflammatory Disease Activity and Assessment of Skin Disease: Frequency Table and Treatment Comparison in Part 2 (Using LOCF, ITT Population)
Physician's Global Assessment of Auto Inflammatory Disease Activity â€“ n (%)
Assessment of Skin Disease â€“ n (%)
Randomized patients in Part 2 treated with ILARIS whose disease flare did not resolve, or who had persistent disease activity from Day 8 up to Day 14 (Physicianâ€™s Global Assessment [PGA] greater than or equal to 2 or C-reactive Protein [CRP] greater than 10 mg/L and no reduction by at least 40% from baseline) received an additional dose of 150 mg (or 2 mg/kg for patients weighing less than or equal to 40 kg). Patients treated with ILARIS whose disease flare did not resolve, or who had persistent disease activity from Day 15 up to Day 28 (PGA greater than or equal to 2 or CRP greater than 10 mg/L and no reduction by at least 70% from baseline), also received an additional dose of 150 mg (or 2 mg/kg for patients weighing less than or equal to 40 kg). On or after Day 29, patients treated with ILARIS in Part 2 with PGA greater than or equal to 2 and CRP greater than or equal to 30 mg/L were also up-titrated. All up-titrated patients remained at the increased dose of 300 mg (or 4 mg/kg for patients weighing less than or equal to 40 kg) every 4 weeks.
The primary efficacy endpoint of the randomized, 16-week treatment period (Part 2) was the proportion of complete responders within each cohort as defined by patients who had resolution of their index disease flare at Day 15 and did not experience a new disease flare during the remainder of the 16-week treatment period. Resolution of the index disease flare (initial flare at the time of the randomization) was defined at the Day 15 visit as a Physicianâ€™s Global Assessment (PGA) Disease Activity score less than 2 (â€œminimal or no diseaseâ€) and C-reactive Protein (CRP) within normal range (less than or equal to 10 mg/L) or reduction greater than or equal to 70% from baseline. The key signs and symptoms assessed in the PGA for each condition were the following: TRAPS: abdominal pain, skin rash, musculoskeletal pain, eye manifestations; HIDS/MKD: abdominal pain; lymphadenopathy, aphthous ulcers; FMF: abdominal pain, skin rash, chest pain, arthralgia/arthritis. A new flare was defined as a PGA score greater than or equal to 2 (â€œmild, moderate, or severe diseaseâ€) and CRP greater to or equal than 30 mg/L. In the 16-week treatment period (Part 2), patients who needed dose escalation, who crossed over from placebo to ILARIS, or who discontinued from the study due to any reason prior to Week 16 were considered as non-responders.
Carton of 1 vialâ€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦.NDC 0078-0582-61
Carton of 1 vialâ€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦.NDC 0078-0734-61
are scheduled to receive any immunizations (vaccines). You should not get â€˜live vaccinesâ€™ if you are receiving ILARIS.
See â€œWhat is the most important information I should know about ILARIS?â€
Periodic Fever Syndromes is the name for several different autoinflammatory diseases, including CAPS, TRAPS, HIDS/MKD, and FMF. People with these diseases cannot keep certain chemicals made by their body (interleukin-1 beta, also called IL-1Î²) at the correct level. All these diseases have symptoms that often come and go, with irritated body parts (inflammation) and elevated body temperature (fever). These conditions have a dysregulation of IL-1Î² production and share similar clinical features of recurrent episodes of inflammation and fever such as rash, headache, pain (mostly in the joints, belly, eyes, muscles), fatigue, inflammation of other organs such as heart, lungs, spleen, and brain.
SJIA is an autoinflammatory disorder which can be caused by having too much or being too sensitive to certain proteins, including interleukin-1Î² (IL-1Î²), and can lead to symptoms such as fever, rash, headache, feeling very tired (fatigue), or painful joints and muscles.
Package Label â€“ 150 mg/vial
Package Label â€“ 150 mg/mL