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Lysosomal Storage Disorder Agents
Recombinant human lysosomal acid lipase (rhLAL) proteinUsed for lysosomal acid lipase (LAL) deficiencyDosed once weekly in infants with rapidly progressive LAL deficiency; dosed once every other week in pediatric and adult patients with LAL deficiency
Kanuma Intravenous Inj Sol: 1mL, 2mg
1 mg/kg/dose IV infusion administered once weekly. For patients not achieving an optimal clinical response, increase dose to 3 mg/kg/dose IV once weekly.
1 mg/kg/dose IV infusion administered once every other week.
1 mg/kg/dose IV once every other week.
3 mg/kg/dose IV weekly for patients with rapidly progressive LAL deficiency; 1 mg/kg/dose IV once every other week for all other patients.
Although neonates were not included in clinical trials, if the drug is used in this population, do not exceed the maximum recommended dose for infants: 3 mg/kg/dose IV weekly for patients with rapidly progressive LAL deficiency; 1 mg/kg/dose IV once every other week for all other patients.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.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.
DilutionDetermine the number of vials needed based on the calculated dose. Remove vials from the refrigerator and allow them to reach room temperature before withdrawing the dose.Dilute sebelipase alfa with an appropriate amount of 0.9% NaCl injection to achieve the recommended final volume for infusion (final concentration should be between 0.1 mg/mL and 1.5 mg/mL). The total infusion volume is based on the prescribed dose and patient weight:For a 1 mg/kg dose the total infusion volumes (mL) are as follows:Patient weight 1 to 10.9 kg: 10 mL final infusion volumePatient weight 11 to 24.9 kg: 25 mL final infusion volumePatient weight 25 to 49.9 kg: 50 mL final infusion volumePatient weight 50 to 99.9 kg: 100 mL final infusion volumePatient weight 100 to 120.9 kg: 250 mL final infusion volumeFor a 3 mg/kg dose the total infusion volumes (mL) are as follows:Patient weight 1 to 10.9 kg: 25 mL final infusion volumePatient weight 11 to 24.9 kg: 50 mL final infusion volumePatient weight 25 to 49.9 kg: 100 mL final infusion volumePatient weight 50 to 99.9 kg: 250 mL final infusion volumePatient weight 100 to 120.9 kg: 500 mL final infusion volumeMix gently by inversion. Do NOT shake the vials or the prepared infusion.Vials are for single-use only. Discard any unused product. Do not freeze.Storage: Use immediately after dilution; vial does not contain preservatives. If immediate use is not possible, diluted product may be stored for up to 24 hours in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F). Do not freeze or shake. Protect from light. Intermittent IV InfusionAdminister the diluted solution using a low-protein binding infusion set equipped with a low-protein binding 0.2 micron in-line filter.Infuse over at least 2 hours. Consider prolonging the infusion time for patients receiving the 3 mg/kg dose or those who have experienced hypersensitivity reactions.A 1-hour infusion may be considered for those patients receiving the 1 mg/kg dose who tolerate the infusion.
Kanuma:- Discard product if it contains particulate matter, is cloudy, or discolored- Do not freeze- Protect from light- Store in original carton in refrigerator (35 to 46 degrees F) until time of use
At the time of FDA approval, the product labeling reported no contraindications for the use of sebelipase alfa in patients with Lysosomal Acid Lipase (LAL) deficiency.
Due to the risk of serious hypersensitivity reactions or anaphylaxis, the administration of sebelipase alfa requires a specialized care setting and readily available medical support. Anaphylaxis has occurred as early as the sixth infusion and as late as 1 year after treatment initiation. If anaphylaxis or other severe hypersensitivity reaction occurs, immediately discontinue the infusion and initiate appropriate medical treatment. Consider the risks and benefits of administering future doses of sebelipase after a severe reaction. If a less severe reaction occurs, management depends on the severity and may include temporarily interrupting the infusion, slowing 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.
Sebelipase alfa is produced in the egg whites of genetically engineered chickens. Patients with a known egg hypersensitivity were excluded from clinical trials. Consider the risks and benefits of treatment with sebelipase alfa in patients with known systemic hypersensitivity reactions to eggs or egg products.
There are no available data regarding sebelipase alfa use during human pregnancy to inform a drug-associated risk. Animal data (rats and rabbits) did not reveal evidence of impaired fertility or harm to the fetus when sebelipase alfa was administered during the period of organogenesis at doses resulting in exposures up to 164 and 526 times the exposure at the recommended human dosage of 1 mg/kg every other week.
There are no data on the presence of sebelipase alfa in animal or human milk, the effects on breast-feeding infants, or the effects on milk production.
anaphylactic shock / Rapid / Incidence not known
antibody formation / Delayed / 14.0-57.0anemia / Delayed / 0-44.0constipation / Delayed / 8.0-8.0edema / Delayed / 1.8hypertension / Early / 1.8hypotonia / Delayed / Incidence not knowntachypnea / Early / Incidence not knownchest pain (unspecified) / Early / Incidence not knowndyspnea / Early / Incidence not knownhyperemia / Delayed / Incidence not knownhyperlipidemia / Delayed / Incidence not known
diarrhea / Early / 0-67.0vomiting / Early / 0-67.0rhinitis / Early / 0-56.0fever / Early / 25.0-56.0pharyngitis / Delayed / 11.0-33.0cough / Delayed / 0-33.0urticaria / Rapid / 0-33.0headache / Early / 28.0-28.0nausea / Early / 8.0-8.0asthenia / Delayed / 8.0-8.0irritability / Delayed / 1.8pallor / Early / 1.8agitation / Early / 1.8rash / Early / 1.8chills / Rapid / 1.8abdominal pain / Early / 1.8sneezing / Early / Incidence not knownanxiety / Delayed / Incidence not knownpruritus / Rapid / Incidence not knownrhinorrhea / Early / Incidence not known
There are no drug interactions associated with Sebelipase alfa products.
Lysosomal acid lipase (LAL) deficiency is an autosomal recessive genetic lysosomal storage disorder that results in a marked decrease or loss in activity of the LAL enzyme, which normally breaks down lipid particles including LDL-c. Deficient LAL enzyme activity results in an accumulation of fats within the cells and progressive complications in multiple organs, including the liver, spleen, intestine, and the walls of blood vessels. Lipid accumulation in the liver can lead to increased liver fat content and progression of liver disease, including fibrosis and cirrhosis, accumulation in the intestinal wall leads to malabsorption and growth failure, and accumulation in blood vessels can lead to premature cardiovascular disease. Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL) that functions in place of the missing or inactive LAL protein. The drug binds to cell surface receptors via glycans expressed on the protein and is internalized into lysosomes. Sebelipase alfa catalyzes the lysosomal hydrolysis of cholesteryl esters and triglycerides to fee cholesterol, glycerol and free fatty acids.
Sebelipase alfa is administered as an intravenous infusion. Its pharmacokinetics were nonlinear with a greater than dose-proportional increase in exposure between 1 and 3 mg/kg based on non-compartmental analysis of data from 26 adults. No accumulation was observed after once weekly or once every other week dosing. Using a population pharmacokinetic model, pharmacokinetic parameters were estimated for 65 patients, including 18 adults, who received sebelipase alfa 1 mg/kg/dose IV once every other week. At week 22, the pharmacokinetic profiles were similar between adolescents and adults. The Tmax (1.1 to 1.3 hours) and t1/2 (5.4 to 6.6 minutes) were similar across all age groups. The following mean PK parameters were calculated for adults: Cmax = 957 +/- 303 ng/mL, AUC = 1,861 +/- 599 h x ng/mL, clearance = 38.2 +/- 12.5 L/h, central volume of distribution = 6.6 +/- 3.7 L. In clinical trials, LDL-c and triglycerides increased within the first 2 to 4 weeks after initiation of treatment with sebelipase alfa. In general, after increases in LDL-c and triglycerides, these parameters decreased to below pre-treatment values within 8 weeks of treatment. Reductions in ALT values were observed, generally within 2 weeks after initiation of treatment. Treatment interruption resulted in increases in LDL-c and ALT values and decrease in HDL-c.