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Sebelipase Alfa

Pronunciation

(se be LYE pase AL fa)

Index Terms

  • SBC-102

Dosage Forms

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)]

Brand Names: U.S.

  • Kanuma

Pharmacologic Category

  • Enzyme, Replacement Therapy

Pharmacology

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.

Distribution

Pediatric patients: Vd:

4 to 11 years: 3.6 ± 3 L

12 to 17 years: 5.4 ± 2.4 L

Adults: Vd: 5.3 ± 1.6 L

Onset of Action

LDL-c and triglycerides reduction: Within 8 weeks; a transient increase in these values occurs during first 1 to 4 weeks of treatment.

ALT reduction: Within 2 weeks.

Time to Peak

Serum: Children ≥4 years, Adolescents, and Adults: Mean range: 1.1 to 1.3 hours

Duration of Action

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

Half-Life Elimination

Children ≥4 years, Adolescents, and Adults: Mean range: 5.4 to 6.6 minutes

Use: Labeled Indications

Lysosomal acid lipase deficiency: Treatment of patients with lysosomal acid lipase (LAL) deficiency

Contraindications

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

Dosing: Adult

Lysosomal acid lipase (LAL) deficiency: IV: 1 mg/kg every other week

Dosing: Geriatric

LAL deficiency: Refer to adult dosing; has not been studied.

Dosing: Pediatric

Rapidly progressive lysosomal acid lipase (LAL) deficiency presenting within the first 6 months of life: Infants: IV: Initial: 1 mg/kg once weekly; if response not optimal, may increase to 3 mg/kg once weekly

LAL deficiency: Infants, Children, and Adolescents: IV: Refer to adult dosing.

Dosing: Renal Impairment

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

Dosing: Hepatic Impairment

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

Dosing: Adjustment for Toxicity

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

Severe hypersensitivity reaction or anaphylaxis: Immediately discontinue infusion.

Reconstitution

Determine number of vials necessary for dose. After allowing vial(s) to reach room temperature, further dilute calculated dose volume with NS up to the manufacturer-recommended total infusion volume based on patient weight (refer to manufacturer’s product labeling) to a final concentration range of 0.1 to 1.5 mg/mL. Mix gently by inversion. Do not shake vials or prepared infusion. Reconstituted solution should be clear to slightly opalescent, colorless to slightly colored solution. Thin, translucent particles or fibers may be present in vials or diluted solution. Vials are for single use only.

Administration

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 3 mg/kg dose or if hypersensitivity reaction occurs.

Compatibility

Stable in NS.

Storage

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.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Frequency not always defined. Incidences are reported for children, adolescents, and adult patients unless specified otherwise.

Cardiovascular: Chest discomfort, oxygen saturation decreased (infants), tachycardia (infants)

Central nervous system: Headache (28%), anxiety, hypotonia (infants)

Dermatologic: Urticaria (infants: 33%)

Endocrine & metabolic: Increase in LDL cholesterol (81%; mean increase of 18% at 2 and 4 weeks postinitiation), increased serum triglycerides (58%; mild increases that are transient)

Gastrointestinal: Diarrhea (infants: 67%), vomiting (infants: 67%), constipation (8%), nausea (8%), retching (infants)

Hematologic & oncologic: Anemia (infants: 44%)

Hypersensitivity: Hypersensitivity reaction (20%; infants: 64%; children, adolescents, and adults: 13%), anaphylaxis (3%; may be delayed as late as 1 year after treatment initiation)

Immunologic: Immunogenicity (infants: ≤57%; neutralizing and may affect drug efficacy: 29%; children, adolescents, and adults: 14%; neutralizing without any association on drug efficacy: 6%)

Neuromuscular & skeletal: Weakness (8%)

Respiratory: Rhinitis (infants: 56%), cough (infants: 33%), nasopharyngitis (infants: 33%; children and adult patients: 11%), oropharyngeal pain (17%), sneezing (infants)

Miscellaneous: Fever (infants: 56%; children and adult patients: 25%)

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.

Monitoring Parameters

Signs and symptoms of hypersensitivity reaction (during infusion and for at least 4 hours after completion of infusion); lipid panel; anti-drug antibody assessment; hepatic function (ALT).

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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience cough, nasal irritation, throat irritation, or constipation. Have patient report immediately to prescriber angina, tachycardia, shortness of breath, eyelid edema, rhinorrhea, fast breathing, abdominal pain, agitation, chills, severe diarrhea, edema, severe headache, severe dizziness, passing out, irritability, severe nausea, severe vomiting, pale skin, or severe loss of strength and energy (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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