Dosing and uses of Kanuma (sebelipase alfa)
Adult dosage forms and strengths
solution for injection
- 20mg/10mL per vial (2mg/mL)
Lysosomal Acid Lipase Deficiency
Indicated for enzyme replacement in patients with lysosomal acid lipase (LAL) deficiency
1 mg/kg IV infusion administered every other week (see Administration)
Pediatric dosage forms and strengths
solution for injection
- 20mg/10mL per vial (2mg/mL)
Lysosomal Acid Lipase Deficiency
Indicated for enzyme replacement in patients with lysosomal acid lipase (LAL) deficiency
1 mg/kg IV infusion administered every other week (see Administration)
Rapidly progressive LAL deficiency presenting within the first 6 months of life
- Starting dose: 1 mg/kg IV infusion administered once weekly
- May increase to 3 mg/kg once weekly for patients who do not achieve an optimal clinical response with the starting dose
Kanuma (sebelipase alfa) adverse (side) effects
>10%
Age <6 months
- Diarrhea (67%)
- Vomiting (67%)
- Fever (56%)
- Rhinitis (56%)
- Anemia (44%)
- Cough (33%)
- Nasopharyngitis (33%)
- Urticaria (33%)
Pediatric and adults
- Headache (28%)
- Fever (25%)
- Oropharyngeal pain (17%)
- Nasopharyngitis (11%)
1-10%
Pediatric and adults
- Asthenia (8%)
- Constipation (8%)
- Nausea (8%)
Warnings
Contraindications
None
Cautions
Hypersensitivity reactions, including anaphylaxis, have been reported as early as the sixth infusion and as late as 1 yr after treatment initiation; symptoms during the infusion may include chest discomfort, conjunctival injection, dyspnea, generalized and itchy rash, hyperemia, swelling of eyelids, rhinorrhea, severe respiratory distress, tachycardia, tachypnea, and urticaria; monitor closely during IV infusion; may need to slow the infusion rate or temporarily interrupt the infusion; discontinue if severe signs and symptoms occur; treat with appropriate medical support
Product 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 risks and benefits in patients with known systemic hypersensitivity reactions to eggs or egg products
Pregnancy
Pregnancy
There are no available data in pregnant women to inform any drug-associated risk
Animal reproductive studies conducted with sebelipase alfa showed no evidence of embryolethality, fetotoxicity, teratogenicity, or abnormal early embryonic development at dosages up to 164 and 526 times the human dosage of 1 mg/kg every other week (based on AUC) in rats and rabbits, respectively
Lactation
Unknown if distributed in human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Kanuma (sebelipase alfa)
Mechanism of action
Recombinant form of the human lysosomal acid lipase (LAL) enzyme
LAL deficiency is an autosomal recessive lysosomal storage disorder characterized by a genetic defect resulting in a marked decrease or loss in activity of LAL enzyme
The primary site of action of the LAL enzyme is the lysosome, where the enzyme normally causes the breakdown of lipid particles, including LDL-c; deficient LAL enzyme activity results in progressive complications due to the lysosomal accumulation of cholesteryl esters and triglycerides in multiple organs, including the liver, spleen, intestine, and walls of blood vessels; the resulting lipid accumulation in the liver may lead to increased liver fat content and progression of liver disease, including fibrosis and cirrhosis
Lipid accumulation in the intestinal wall leads to malabsorption and growth failure; in parallel, dyslipidemia due to impaired degradation of lysosomal lipid is common with elevated LDL-c and triglycerides and low HDL-c
Absorption
Peak plasma time: 1.1-1.3 hr
Peak plasma concentration: 490-957 ng/mL
AUC: 942-1861 ng·hr/mL
Distribution
Vd: 3.6-5.4 L
Elimination
Half-life: 5.4-6.6 minutes
Clearance: 31.1-38.2 L/hr
Administration
IV Preparation
Determine number of vials needed for dose based on patient’s weight; round to the next whole vial and remove the required number of vials from the refrigerator to allow them to reach room temperature
Determine the volume of the calculated dose and the necessary volume of 9% NaCl for dilution; the infusion volume should be based on the prescribed dose and should be prepared to a final concentration of 0.1-1.5 mg/mL (see total volume sections listed below)
Mix gently by inversion; do not shake the vials or the prepared infusion
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
Contains no preservatives; therefore, product should be used immediately after dilution; if this is not possible, may store refrigerated (see Storage)
1 mg/kg dose total infusion volume
- Drug volume plus 0.9% NaCl for dilution
- 1-10.9 kg: 10 mL
- 11-24.9 kg: 25 mL
- 25-49.9 kg: 50 mL
- 50-99.9 kg: 100 mL
- 100-120.9 kg: 250 mL
3 mg/kg dose total infusion volume
- Drug volume plus 0.9% NaCl for dilution
- 1-10.9 kg: 25 mL
- 11-24.9 kg: 50 mL
- 25-49.9 kg: 100 mL
- 50-99.9 kg: 250 mL
- 100-120.9 kg: 500 mL
IV Administration
Administer IV infusion using a low-protein binding infusion set with an in-line, low-protein binding 0.2 micron filter
Infuse over at least 2 hr
Consider further prolonging the infusion time for patients receiving the 3 mg/kg dose or those who have experienced hypersensitivity reactions (see Cautions)
A 1-hr infusion may be considered for those patients receiving the 1 mg/kg dose who tolerate the infusion
Storage
Unopened vials
- Refrigerate between 2-8°C (36-46°F) in original carton to protect from light
- Do not shake or freeze the vials
Diluted solution
- If immediate use is not possible, the diluted product may be stored up to 24 hr in the refrigerator at 2-8°C (36-46°F)
- Do not freeze or shake
- Protect from light
