General

Pronunciation:
se-be-lye-pase al-fa

Trade Name(s)

• Kanuma

Ther. Class.

none assigned

Pharm. Class.

enzymes

Indications

Lysosomal acid lipase deficiency.

Action

A recombinant form of lysosomal acid lipase, it binds to cell surface receptors via glycans expressed on the protein and is subsequently internalized into lysosomes. It then catalyzes the lysosomal hydrolysis of cholesteryl esters and triglycerides to free cholesterol, glycerol, and free fatty acids.

Therapeutic Effect(s):

• Improved survival in infants.
• Improved lipids in adults and children.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Well distributed to tissues.

Metabolism and Excretion: Unknown.

Half-life: 5.4–6.6 min.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to eggs.

Use Cautiously in:

• OB:   Safety not established in pregnancy;
• Lactation: Safety not established in breastfeeding;
• Pedi:  Children <1 mo (safety and effectiveness not established);
• Geri:  Older adults (safety and effectiveness not established).

Adverse Reactions/Side Effects

CV: tachycardia

EENT: nasopharyngitis, rhinitis, sneezing

GI: diarrhea, oropharyngeal pain, vomiting, constipation, nausea

Hemat: anemia

Metabolic: ↑ LDL cholesterol, ↑ triglycerides

MS: hypotonia

Neuro: headache, anxiety

Resp: cough, hypoxemia

Misc: fever, HYPERSENSITIVITY REACTIONS (including anaphylaxis, urticaria)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

Rapidly Progressive Lysosomal Acid Lipase Deficiency Presenting within First 6 Mo of Age

IV Infants: 1 mg/kg once weekly; may ↑ to 3 mg/kg once weekly if suboptimal response (poor growth, deteriorating biochemical markers, or persistent or worsening organomegaly) achieved; may ↑ to 5 mg/kg once weekly if suboptimal response continues to be achieved.

Lysosomal Acid Lipase Deficiency in Children and Adults

IV (Adults and Children): 1 mg/kg every other wk; may ↑ to 3 mg/kg every other wk if suboptimal response (poor growth, deteriorating biochemical markers [e.g., ALT, AST], and/or parameters of lipid metabolism [e.g., LDL cholesterol, triglycerides].

Availability

Solution for injection: 2 mg/mL

Assessment

• Monitor for signs and symptoms of hypersensitivity reactions (chest discomfort, conjunctival injection, dyspnea, generalized and itchy rash, hyperemia, swelling of eyelids, rhinorrhea, severe respiratory distress, tachycardia, tachypnea, urticaria) during and after infusion. Anaphylaxis has occurred as early as the 6th infusion and as late as 1 yr after treatment initiation. If hypersensitivity reaction occurs, ↓ infusion rate and treat with antihistamines, antipyretics, and/or corticosteroids. If anaphylaxis occurs, discontinue infusion and initiate symptomatic treatment.
• Assess allergies and hypersensitivity to eggs or egg products. Consider the risks and benefits of treatment in known systemic reactions.

Lab Test Considerations:

May cause ↑ circulating LDL cholesterol and triglycerides.

Implementation

• Administer antihistamine, antipyretics, and/or corticosteroids prior to infusion, if required, to prevent hypersensitivity reactions.
• Administer in a health care setting with appropriate medical monitoring and supportive measures (cardiopulmonary resuscitation equipment) available during administration.
• If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue immediately and initiate appropriate medical treatment (epinephrine). Consider the risks and benefits of readministering following severe hypersensitivity reactions.
• Intermittent Infusion:  Remove solution vials from refrigerator and allow to reach room temperature. Follow recommended calculations per manufacture guidelines. Dilution:  Dilute with 0.9% NaCl.  For 1 mg/kg dose,  dilute each mL for 1–2.9 kg in 4 mL, 3–5.9 kg in 6 mL, 6–10.9 kg in 10 mL, 11–24.9 kg in 25 mL, 25–49.9 kg in 50 mL, 50–99.9 kg in 100 mL, and 100–120.9 kg in 250 mL.  For 3 mg/kg dose,  dilute each mL for 1–2.9 kg in 8 mL, 3–5.9 kg in 12 mL, 6–10.9 kg in 25 mL, 11–24.9 kg in 50 mL, 25–49.9 kg in 100 mL, 50–99.9 kg in 250 mL, and 100–120.9 kg in 500 mL.  For 5 mg/kg dose, dilute each mL for 1–2.9 kg in 12 mL, 3–5.9 kg in 20 mL, 6–10.9 kg in 50 mL, 11–24.9 kg in 150 mL, 25–49.9 kg in 250 mL, 50–99.9 kg in 500 mL, and 100–120.9 kg in 600 mL.  Concentration: 0.1–1.5 mg/mL. Mix gently by inversion; do not shake. Solution is clear to slightly opalescent, colorless to slightly colored, and may contain thin, translucent particles or fibers. Do not use solutions that are cloudy or contain other particulate matter. Discard unused portions of vials. Administer immediately after dilution; diluted solution may be stored up to 24 hr in refrigerator. Infuse via in-line low-protein-binding 0.2 micron filter through a low-protein-binding infusion set.
• Rate: Infuse over ≥2 hr. Patients receiving >1 mg/kg or having experienced hypersensitivity reactions may require longer infusion. A 1-hr infusion may be used in patients who tolerate 1 mg/kg dose.

Patient/Family Teaching

• Explain purpose and side effects of sebelipase alfa to patient and/or caregiver.
• Advise patient and/or caregiver to read Patient Information  before starting therapy.
• Advise patient and/or caregiver to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
• Teach patient and/or caregiver the signs and symptoms of an hypersensitivity reaction; if any occur, seek immediate medical care.
• Advise patient and/or caregiver to report known allergies to eggs or egg products prior to treatment.
• Advise patient and/or caregiver if a dose is missed to notify a health care professional.
• Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

• Improved survival in infants.
• Improved lipids in adults and children.