KANUMA- sebelipase alfa injection, solution, concentrate
Alexion Pharmaceuticals, Inc.
1 INDICATIONS AND USAGE
KANUMA™ is indicated for the treatment of patients with a diagnosis of Lysosomal Acid Lipase (LAL) deficiency.
2 DOSAGE AND ADMINISTRATION
Patients with Rapidly Progressive LAL Deficiency Presenting within the First 6 Months of Life:
The recommended starting dosage is 1 mg/kg administered once weekly as an intravenous infusion. For patients who do not achieve an optimal clinical response, increase to 3 mg/kg once weekly.
Pediatric and Adult Patients with LAL Deficiency:
The recommended dosage is 1 mg/kg administered once every other week as an intravenous infusion.
2.2 Preparation Instructions
KANUMA is for intravenous infusion only. Prepare KANUMA using the following steps.
Determine the number of vials needed based on the patient's weight and the recommended dose of 1 mg/kg or 3 mg/kg, using the following calculations (a-b):
Total dose (mg) = Patient's weight (kg) × Recommended dose (mg/kg)
Total number of vials = Total dose (mg) divided by 20 mg/vial
Round to the next whole vial and remove the required number of vials from the refrigerator to allow them to reach room temperature.
Volume (mL) of calculated total dose = Total dose (mg) divided by the 2 mg/mL concentration
Volume (mL) of 0.9% Sodium Chloride for dilution = Total infusion volume (mL) for patient's weight (see Table 1) – Volume (mL) of calculated total dose
Table 1: Total Infusion Volumes *Weight Range (kg) 1 mg/kg dose 3 mg/kg dose †
Total Infusion Volume (mL) Total Infusion Volume (mL)
The infusion volume should be based on the prescribed dose and should be prepared to a final KANUMA concentration of 0.1 mg/mL to 1.5 mg/mL.
For patients with LAL deficiency presenting within the first 6 months of life who do not achieve an optimal clinical response with a dose of 1 mg/kg.
1 to 10.9 10 25
11 to 24.9 25 50
25 to 49.9 50 100
50 to 99.9 100 250
100 to 120.9 250 500
Mix gently by inversion. Do not shake the vials or the prepared infusion.
The solution should be inspected visually for particulate matter and discoloration prior to administration. The solution should be a clear to slightly opalescent, colorless to slightly colored solution. Thin, translucent particles or fibers may be present in the vials or diluted solution. Do not use if the solution is cloudy or if other particulate matter is observed.
Vials are for single-use only. Discard any unused product. Do not freeze.
2.3 Administration Instructions
Administer the diluted solution as an intravenous infusion using a low-protein binding infusion set with an in-line, low-protein binding 0.2 micron filter.
Infuse over at least 2 hours. Consider further prolonging the infusion time for patients receiving the 3 mg/kg dose or those who have experienced hypersensitivity reactions [see Warnings and Precautions (5.1)]. A 1-hour infusion may be considered for those patients receiving the 1 mg/kg dose who tolerate the infusion.
2.4 Storage of Diluted Solution
KANUMA contains no preservatives; therefore, product should be used immediately after dilution. If immediate use is not possible, the diluted product may be stored up to 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light.
3 DOSAGE FORMS AND STRENGTHS
Injection: 20 mg/10 mL (2 mg/mL) solution in single-use vials.
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions Including Anaphylaxis
Hypersensitivity reactions, including anaphylaxis, have been reported in KANUMA-treated patients. In clinical trials, 3 of 106 (3%) patients treated with KANUMA experienced signs and symptoms consistent with anaphylaxis. These patients experienced reactions during infusion with signs and symptoms including chest discomfort, conjunctival injection, dyspnea, generalized and itchy rash, hyperemia, swelling of eyelids, rhinorrhea, severe respiratory distress, tachycardia, tachypnea, and urticaria. Anaphylaxis has occurred as early as the sixth infusion and as late as 1 year after treatment initiation.
In clinical trials, 21 of 106 (20%) KANUMA-treated patients, including 9 of 14 (64%) infants and 12 of 92 (13%) pediatric patients, 4 years and older, and adults, experienced signs and symptoms either consistent with or that may be related to a hypersensitivity reaction. Signs and symptoms of hypersensitivity reactions, occurring in two or more patients, included abdominal pain, agitation, fever, chills, diarrhea, eczema, edema, hypertension, irritability, laryngeal edema, nausea, pallor, pruritus, rash, and vomiting. The majority of reactions occurred during or within 4 hours of the completion of the infusion. Patients were not routinely pre-medicated prior to infusion of KANUMA in these clinical trials.
Due to the potential for anaphylaxis, appropriate medical support should be readily available when KANUMA is administered. If anaphylaxis occurs, immediately discontinue the infusion and initiate appropriate medical treatment. Observe patients closely during and after the infusion. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur.
The management of hypersensitivity reactions should be based on the severity of the reaction and may include temporarily interrupting the infusion, lowering the infusion rate, and/or treatment with antihistamines, antipyretics, and/or corticosteroids. If interrupted, the infusion may be resumed at a slower rate with increases as tolerated. Pre-treatment with antipyretics and/or antihistamines may prevent subsequent reactions in those cases where symptomatic treatment was required. If a severe hypersensitivity reaction occurs, immediately discontinue the infusion and initiate appropriate medical treatment.
Consider the risks and benefits of re-administering KANUMA following a severe reaction. Monitor patients, with appropriate resuscitation measures available, if the decision is made to re-administer the product.
5.2 Hypersensitivity to Eggs or Egg Products
KANUMA is produced in the egg whites of genetically engineered chickens. Patients with a known history of egg allergies were excluded from the clinical trials. Consider the risks and benefits of treatment with KANUMA in patients with known systemic hypersensitivity reactions to eggs or egg products.
6 ADVERSE REACTIONS
6.1 Clinical Trials 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 clinical practice.
In clinical trials, a total of 106 patients received treatment with KANUMA. The data described below reflect exposure to KANUMA in 75 patients who received KANUMA at dosages up to 3 mg/kg once weekly in clinical trials:
Nine patients (5 males, 4 females) who had growth failure or other evidence of rapidly progressive LAL deficiency presenting within the first 6 months of life received KANUMA for up to 165 weeks (median 60 weeks) at escalating doses ranging between 0.35 mg/kg and 5 mg/kg once weekly [see Clinical Studies (14.1)]. The recommended initial dosage for these patients is 1 mg/kg escalating to 3 mg/kg once weekly [see Dosage and Administration (2.1)].
66 pediatric and adult patients with LAL deficiency aged 4 to 58 years (33 males, 33 females) received KANUMA 1 mg/kg every other week up to 36 weeks.
Table 2 summarizes the most common adverse reactions occurring in >30% of patients with rapidly progressive LAL deficiency presenting within the first 6 months of life receiving KANUMA.