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Sebelipase alfa: Pediatric drug information

Sebelipase alfa: Pediatric drug information
(For additional information see "Sebelipase alfa: Drug information" and see "Sebelipase alfa: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Kanuma
Brand Names: Canada
  • Kanuma
Therapeutic Category
  • Enzyme, Replacement Therapy
Dosing: Pediatric
Lysosomal acid lipase deficiency; rapidly progressive presenting within the first 6 months of life

Lysosomal acid lipase (LAL) deficiency; rapidly progressive presenting within the first 6 months of life:

Infants, Children, and Adolescents: IV: Initial: 1 mg/kg/dose once weekly; may increase to 3 mg/kg/dose once weekly if response not optimal; if response remains not optimal may further increase to 5 mg/kg/dose once weekly. Suboptimal response may include poor growth, deteriorating biochemical markers, or persistent/worsening organomegaly. In the trials, dose titration to 3 mg/kg dose was reported between 4 and 88 weeks after initial treatment dose (median: 11 weeks). The time point in which dosing was escalated to 5 mg/kg in the 2 continuation treatment trials was not described; median duration of exposure to 5 mg/kg was 33 months (range: 27 to 39 months) and 15 months (range: 5 to 24 months) in the 2 treatment groups.

Lysosomal acid lipase deficiency

Lysosomal acid lipase (LAL) deficiency: Infants, Children, and Adolescents: IV: Initial: 1 mg/kg/dose every other week; may increase to 3 mg/kg/dose every other week if response not optimal. Suboptimal response may include poor growth and deteriorating biochemical markers (eg, ALT, AST) and/or parameters of lipid metabolism (eg, LDL-C, triglycerides).

Dosing adjustment for toxicity: All patients:

Mild or moderate hypersensitivity reaction: Interrupt infusion; consider resuming at slower infusion rate.

Severe hypersensitivity reaction or anaphylaxis: Immediately discontinue infusion.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Adult

(For additional information see "Sebelipase alfa: Drug information")

Lysosomal acid lipase deficiency

Lysosomal acid lipase deficiency: IV: 1 mg/kg every other week; may increase to 3 mg/kg every other week in patients with suboptimal response (poor growth, deteriorating biochemical markers [eg, ALT, AST], and/or parameters of lipid metabolism [eg, low-density lipoprotein cholesterol, triglycerides]).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences are reported for infants, pediatrics, and adults unless specified otherwise.

>10%:

Cardiovascular: Tachycardia (infants)

Dermatologic: Urticaria (infants)

Endocrine & metabolic: Increase in LDL cholesterol (children, adolescents, and adults), increased serum triglycerides (children, adolescents, and adults)

Gastrointestinal: Diarrhea, vomiting (infants)

Hematologic & oncologic: Anemia (infants)

Hypersensitivity: Hypersensitivity reaction

Immunologic: Antibody development (may be neutralizing)

Nervous system: Headache (children, adolescents, and adults)

Respiratory: Cough (infants), nasopharyngitis, oropharyngeal pain (children, adolescents, and adults), respiratory distress (infants), rhinitis (infants)

Miscellaneous: Fever

1% to 10%:

Gastrointestinal: Abdominal pain (children, adolescents, and adults), constipation (children, adolescents, and adults), nausea (children, adolescents, and adults)

Hypersensitivity: Anaphylaxis (infants: May be delayed as late as 1 year after treatment initiation)

Nervous system: Dizziness (children, adolescents, and adults)

Neuromuscular & skeletal: Asthenia (children, adolescents, and adults)

Frequency not defined (any population):

Cardiovascular: Chest discomfort, oxygen saturation decreased

Gastrointestinal: Retching

Nervous system: Anxiety, hypotonia

Respiratory: Sneezing

Contraindications

There are no contraindications listed within the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to sebelipase alfa or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: Hypersensitivity reactions have occurred during infusion and within 4 hours after the infusion. Anaphylaxis has occurred as early as the sixth infusion and as late as 1 year after treatment initiation. During infusion, appropriate medical treatment should be immediately available. Depending on severity of hypersensitivity reaction, management may include temporary interruption, lowering infusion rate, and/or administration of antihistamines, antipyretics, and/or corticosteroids. If interrupted, the infusion may be resumed at a slower rate with increases as tolerated. Pretreatment with antipyretics and/or antihistamines may prevent subsequent reactions in those cases where symptomatic treatment was required. If anaphylaxis or severe hypersensitivity occurs, immediately discontinue infusion and initiate appropriate medical treatment.

• Antibody formation: Patients have developed anti-drug antibodies (ADA) to sebelipase alfa and may be more likely to experience hypersensitivity reactions. Some patients with neutralizing antibodies experienced decreased growth velocity. No clear association exists between the development of ADA and decreased efficacy in patients.

Dosage form specific issues:

• Allergy to egg or egg products: Sebelipase alfa is produced in egg whites of genetically engineered chickens; consider the risks and benefits in patients with known systemic hypersensitivity reactions to eggs or egg products.

Warnings: Additional Pediatric Considerations

From clinical trials, the reported incidence of hypersensitivity reactions was 20% for all patients (21 of 106 patients); however, the incidence in the infant age group was 64% (nine of 14 patients); patients were not premedicated prior to sebelipase alfa infusions during the trials. Hypersensitivity reaction presentation in two or more patients included the following signs and symptoms: Abdominal pain, agitation, fever, chills, diarrhea, eczema, edema, hypertension, irritability, laryngeal edema, nausea, pallor, pruritus, rash, and vomiting.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Kanuma: 20 mg/10 mL (10 mL) [contains albumin human, egg white (egg protein)]

Generic Equivalent Available: US

No

Pricing: US

Solution (Kanuma Intravenous)

20 mg/10 mL (per mL): $1,225.20

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Kanuma: 20 mg/10 mL (10 mL) [contains albumin human, egg white (egg protein)]

Administration: Pediatric

Parenteral: IV infusion: Administer diluted solution (0.1 to 1.5 mg/mL) using low-protein-binding infusion set with in-line, low-protein-binding 0.2 micron filter. Infuse IV over at least 2 hours; may consider 1-hour infusion for those patients receiving 1 mg/kg dose who tolerate a 2-hour infusion. Consider further prolonging infusion time for doses >1 mg/kg/dose or if hypersensitivity reaction occurs.

Administration: Adult

IV: Administer diluted solution as an IV infusion using low-protein-binding infusion set with in-line, low-protein-binding 0.2 micron filter. Infuse over at least 2 hours; may consider 1-hour infusion for those patients receiving 1 mg/kg dose who tolerate a 2-hour infusion. Consider further prolonging infusion time for doses >1 mg/kg or if hypersensitivity reaction occurs.

Storage/Stability

Store intact vials under refrigeration between 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not shake or freeze. If not used immediately, reconstituted product may be stored up to 24 hours in the refrigerator.

Use

Treatment of patients with lysosomal acid lipase (LAL) deficiency (FDA approved in ages ≥1 month and adults).

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Sebelipase alfa is a recombinant form of lysosomal acid lipase (LAL), an essential enzyme required for lipid metabolism (Burton 2015; Shirley 2015).

Monitoring Parameters

Signs and symptoms of hypersensitivity reaction (during infusion and for at least 4 hours after completion of infusion); lipid panel (eg, LDL-C, triglycerides); antidrug antibody assessment; hepatic function (eg, ALT, AST); growth parameters.

Mechanism of Action

Sebelipase alfa binds to cell surface receptors via glycans expressed on the protein and is subsequently internalized into lysosomes. Sebelipase alfa catalyzes the lysosomal hydrolysis of cholesteryl esters and triglycerides to free cholesterol, glycerol, and free fatty acids. In patients with lysosomal acid lipase (LAL) deficiency, replacement with sebelipase alfa, a recombinant form of LAL, results in improvement in disease-related hepatic and lipid parameters.

Pharmacokinetics (Adult Data Unless Noted)

Onset:

LDL-c and triglycerides reduction: Within 8 weeks; a transient increase in these values occurs during first 2 to 4 weeks of treatment

ALT reduction: Within 2 weeks.

Duration: Effects on ALT partially reverse 3 weeks after treatment discontinuation (Balwani 2013)

Distribution: Vd:

Pediatric patients:

4 to 11 years: 3.6 ± 3 L

12 to 17 years: 5.4 ± 2.4 L

Adults: 5.3 ± 1.6 L

Half-life elimination: Children ≥4 years, Adolescents, and Adults: Mean range: 5.4 to 6.6 minutes

Time to peak, serum: Children ≥4 years, Adolescents, and Adults: Mean range: 1.1 to 1.3 hours

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Kanuma;
  • (AT) Austria: Kanuma;
  • (BG) Bulgaria: Kanuma;
  • (BR) Brazil: Kanuma;
  • (CO) Colombia: Kanuma;
  • (CZ) Czech Republic: Kanuma;
  • (DE) Germany: Kanuma;
  • (EG) Egypt: Kanuma;
  • (ES) Spain: Kanuma;
  • (FI) Finland: Kanuma;
  • (FR) France: Kanuma;
  • (GB) United Kingdom: Kanuma;
  • (IT) Italy: Kanuma;
  • (JP) Japan: Kanuma;
  • (KR) Korea, Republic of: Kanuma;
  • (MX) Mexico: Kanuma;
  • (NL) Netherlands: Kanuma;
  • (NO) Norway: Kanuma;
  • (PL) Poland: Kanuma;
  • (PR) Puerto Rico: Kanuma;
  • (PT) Portugal: Kanuma;
  • (QA) Qatar: Kanuma;
  • (RO) Romania: Kanuma;
  • (RU) Russian Federation: Kanuma;
  • (SA) Saudi Arabia: Kanuma;
  • (SE) Sweden: Kanuma;
  • (SI) Slovenia: Kanuma
  1. Balwani M, Breen C, Enns GM, et al. Clinical effect and safety profile of recombinant human lysosomal acid lipase in patients with cholesteryl ester storage disease. Hepatology. 2013;58(3):950-957. doi:10.1002/hep.26289. [PubMed 23348766]
  2. Burton BK, Balwani M, Feillet F, et al. A Phase 3 trial of sebelipase alfa in lysosomal acid lipase deficiency. N Engl J Med. 2015;373(11):1010-1020. doi:10.1056/NEJMoa1501365. [PubMed 26352813]
  3. Kanuma (sebelipase alfa) [prescribing information]. Boston, MA: Alexion Pharmaceuticals; November 2021.
  4. Kanuma (sebelipase alfa) [product monograph]. Zurich, Switzerland: Alexion Pharma GmbH; September 2021.
  5. Shirley M. Sebelipase alfa: first global approval. Drugs. 2015;75(16):1935-1940. doi: 10.1007/s40265-015-0479-6. [PubMed 26452566]
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