sebelipase alfa (Rx)

>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%)

Contraindications

None

Cautions

Hypersensitivity reactions

• Hypersensitivity, including anaphylaxis, reported as early as the sixth infusion and as late as 1 yr after treatment initiation
• Owing to potential for anaphylaxis, assure appropriate medical support is readily available during administration
• Management based on reaction severity and may include temporarily interrupting infusion, lowering infusion rate, and/or treatment with antihistamines, antipyretics, and/or corticosteroids
• If interrupted, may resume infusion at 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 severe hypersensitivity reaction occurs, immediately discontinue infusion and initiate appropriate medical treatment

Hypersensitivity to eggs or egg products

• Product is produced in the egg whites of genetically engineered chickens
• Patients with known history of egg allergies were excluded from clinical trials
• Consider risks and benefits with known systemic hypersensitivity reactions to eggs or egg products

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.

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

IV Preparation

Calculate number of vials needed for dose based on patient’s weight (round to next whole vial); remove from refrigeration to allow them to reach room temperature

Determine dosage volume and the necessary volume of 9% NaCl for dilution; infusion volume based on prescribed dose (final concentration of range of 0.1-1.5 mg/mL)

Mix gently by inversion; do not shake vials or diluted solution

Inspected visually for particulate matter and discoloration before administration; solution should be a clear to slightly opalescent, colorless to slightly colored solution; thin, translucent particles or fibers may be present in vials or diluted solution

Discard if solution is cloudy or if other particulate matter observed

Vials are for single use only; discard any unused product

Contains no preservatives; therefore, use product immediately after dilution; if this is not possible, may store refrigerated

1 mg/kg dose total infusion volume

• Drug volume plus 0.9% NaCl for dilution
• 1-2.9 kg: 4 mL
• 3-5.9 kg: 6 mL
• 6-10.9 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
• 1-2.9 kg: 8 mL
• 3-5.9 kg: 12 mL
• 6-10.9 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

5 mg/kg dose total infusion volume

• Drug volume plus 0.9% NaCl for dilution
• 1-2.9 kg: 12 mL
• 3-5.9 kg: 20 mL
• 6-10.9 kg: 50 mL
• 11-24.9 kg: 150 mL
• 25-49.9 kg: 250 mL
• 50-99.9 kg: 500 mL
• 100-120.9 kg: 600 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 infusion time for patients receiving doses >1 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

Diluted solution: If immediate use not possible, diluted product may be refrigerated up to 24 hr at 2-8°C (36-46°F)

Do not freeze or shake

Protect from light