Olipudase alfa: Pediatric drug information

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

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

ALERT: US Boxed Warning

Hypersensitivity reactions including anaphylaxis:

Patients treated with olipudase alfa have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during olipudase alfa administration. If a severe hypersensitivity reaction (eg, anaphylaxis) occurs, discontinue olipudase alfa immediately and initiate appropriate medical treatment. In patients with severe hypersensitivity reactions, a desensitization procedure to olipudase alfa may be considered.

Brand Names: US

Xenpozyme

Therapeutic Category

Enzyme;
Recombinant Human Acid Sphingomyelinase

Dosing: Neonatal

Dosage guidance:

Safety: Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids prior to infusion to prevent infusion reactions.

Acid sphingomyelinase deficiency, non-central nervous system manifestations

Acid sphingomyelinase deficiency (ASMD), non-central nervous system manifestations:

Neonates weighing ≥2 kg:

Initiation and escalation: IV: Administer once every 2 weeks in increasing doses every 2 weeks as per the following table:

**Olipudase Dose Escalation**
Dose number	Week	Dose
1	0	0.03 mg/kg
2	2	0.1 mg/kg
3	4	0.3 mg/kg
4	6	0.3 mg/kg
5	8	0.6 mg/kg
6	10	0.6 mg/kg
7	12	1 mg/kg
8	14	2 mg/kg
9	16	3 mg/kg

Maintenance: IV: 3 mg/kg/dose every 2 weeks; initiate 2 weeks after completion of escalation phase.

Missed doses: If a dose is missed by ≥3 days after the originally scheduled dose, follow the recommendations in the missed dose recommendations table, depending on whether the patient is in the escalation or maintenance phase. IV:

**Olipudase Alfa Missed Dose Recommendations^a**
	Number of consecutive missed doses
	1 missed dose	2 missed doses	3 missed doses
^a For first dose after missed dose(s), if dose to be administered is 0.3 or 0.6 mg/kg, administer that dose twice as per dose escalation regimen.
Dose(s) missed in escalation phase	Administer the last tolerated dose, then resume dose escalation.^a	Administer 1 dose level below the last tolerated dose, then resume dose escalation per olipudase alfa dose escalation table.^a	Administer 0.3 mg/kg for the first dose, then resume dose escalation from that dose level per olipudase alfa dose escalation table.^a
Dose(s) missed in maintenance phase	Administer maintenance dose.	Administer 1 dose level below the maintenance dose, then resume maintenance dosing.	Administer 0.3 mg/kg for the first dose, then escalate dose from that dose level per olipudase alfa dose escalation table.^a

Dosing adjustment for toxicity: Neonates:

Hypersensitivity or infusion-associated reaction:

Mild or moderate: Consider temporarily holding or slowing the infusion rate and/or decreasing the olipudase alfa dose. If dose is reduced, re-escalate following dose escalation table.

Severe (including anaphylaxis): Immediately discontinue olipudase alfa and initiate appropriate medical treatment. Consider the risks and benefits of restarting olipudase alfa.

Hepatic impairment:

Baseline: ALT or AST >2 × ULN: Repeat AST and ALT within 72 hours after the end of the infusion.

During therapy: AST or ALT above baseline and >2 × ULN: Repeat prior dose or reduce one dose level, or temporarily withhold olipudase alfa until ALT and AST return to baseline.

Dosing: Pediatric

Dosage guidance:

Dosing: Dosing weight for dosage calculation dependent on BMI.

BMI ≤30 kg/m²: Use actual body weight.

BMI >30 kg/m²: Use an adjusted body weight based on the following equation:

Adjusted body weight (kg) = (actual height in meters)²× 30

Acid sphingomyelinase deficiency, non-central nervous system manifestations

Acid sphingomyelinase deficiency (ASMD), non-central nervous system manifestations: Note: Consider pretreatment with antihistamines, antipyretics, and/or corticosteroids prior to infusion to prevent infusion reactions.

Initiation and escalation:

Infants, Children, and Adolescents <18 years: IV: Administer once every 2 weeks in increasing doses every 2 weeks as per the following table:

**Olipudase Dose Escalation** **for Ages <18 Years**
Dose number	Week	Dose
1	0	0.03 mg/kg
2	2	0.1 mg/kg
3	4	0.3 mg/kg
4	6	0.3 mg/kg
5	8	0.6 mg/kg
6	10	0.6 mg/kg
7	12	1 mg/kg
8	14	2 mg/kg
9	16	3 mg/kg

Adolescents ≥18 years: IV: Administer once every 2 weeks in increasing doses every 2 weeks as per the following table:

**Olipudase Dose Escalation** **for Ages ≥18 Years**
Dose number	Week	Dose
1	0	0.1 mg/kg
2	2	0.3 mg/kg
3	4	0.3 mg/kg
4	6	0.6 mg/kg
5	8	0.6 mg/kg
6	10	1 mg/kg
7	12	2 mg/kg
8	14	3 mg/kg

Maintenance: Infants, Children, and Adolescents: IV: 3 mg/kg/dose every 2 weeks; initiate 2 weeks after completion of escalation phase.

**Olipudase Alfa Missed Dose Recommendations^a**
	Number of consecutive missed doses
	1 missed dose	2 missed doses	3 missed doses
^a For first dose after missed dose(s), if dose to be administered is 0.3 or 0.6 mg/kg, administer that dose twice as per dose escalation regimen.
Dose(s) missed in escalation phase	Administer the last tolerated dose, then resume dose escalation.^a	Administer 1 dose level below the last tolerated dose, then resume dose escalation per olipudase alfa dose escalation table.^a	Administer 0.3 mg/kg for the first dose, then resume dose escalation from that dose level per olipudase alfa dose escalation table.^a
Dose(s) missed in maintenance phase	Administer maintenance dose.	Administer 1 dose level below the maintenance dose, then resume maintenance dosing.	Administer 0.3 mg/kg for the first dose, then escalate dose from that dose level per olipudase alfa dose escalation table.^a

Dosing adjustment for toxicity: Infants, Children, and Adolescents:

Hypersensitivity or infusion-associated reaction:

Mild or moderate: Consider temporarily holding or slowing the infusion rate and/or decreasing the dose. If dose is reduced, re-escalate following dose escalation table.

Severe (including anaphylaxis): Immediately discontinue olipudase alfa and initiate appropriate medical treatment. Consider the risks and benefits of restarting olipudase alfa.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment: Pediatric

Baseline:

ALT or AST >2 × ULN: Repeat AST and ALT within 72 hours after the end of the infusion.

During therapy:

AST or ALT above baseline and >2 × ULN: Repeat prior dose or reduce one dose level, or temporarily withhold olipudase alfa until ALT and AST return to baseline.

Dosing: Adult

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

Acid sphingomyelinase deficiency

Acid sphingomyelinase deficiency:

Note: Consider premedication with antihistamines, antipyretics, and/or corticosteroids.

Dosing weight: For patients with a BMI ≤30 kg/m², use actual body weight. For patients with BMI >30 kg/m², use adjusted body weight for dosage calculation; adjusted body weight = (actual height in meters)² × 30.

IV infusion: Follow dose escalation regimen and maintenance phase dosing as described below. Doses are administered once every 2 weeks:

**Olipudase Alfa Dose Escalation Regimen and Maintenance Phase Dosing**
Dose number (week)	Dose
1 (Week 0 [Day 1])	0.1 mg/kg
2 (Week 2)	0.3 mg/kg
3 (Week 4)	0.3 mg/kg
4 (Week 6)	0.6 mg/kg
5 (Week 8)	0.6 mg/kg
6 (Week 10)	1 mg/kg
7 (Week 12)	2 mg/kg
8 and maintenance dosing (Week 14 and every 2 weeks thereafter)	3 mg/kg

Missed dose: If a dose is missed by ≥3 days after the originally scheduled dose, follow the dosing recommendations described below. Dosing recommendations differ for dose escalation regimens and maintenance phase regimens:

**Olipudase Alfa Dosing Recommendations Following Missed Dose(s)^a**
	Number of consecutive missed doses
	1 missed dose	2 missed doses	≥3 missed doses
^a For first dose after missed dose(s), if dose to be administered is 0.3 or 0.6 mg/kg, administer that dose twice as per dose escalation regimen.
Dose(s) missed in escalation regimen	Administer last tolerated dose, then resume dose escalation regimen 2 weeks later.^a	Administer 1 dose below last tolerated dose, then resume dose escalation regimen 2 weeks later.^a	Restart dose escalation regimen starting at 0.3 mg/kg.^a
Dose(s) missed in maintenance phase	Administer maintenance dose.	Administer 1 dose below the maintenance dose, then resume maintenance dosing 2 weeks later.	Restart dose escalation regimen starting at 0.3 mg/kg.^a

Dosing: Kidney Impairment: Adult

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

Dosing: Hepatic Impairment: Adult

Hepatotoxicity during treatment:

ALT and/or AST above baseline and >2 times ULN prior to next scheduled treatment: Adjust dose (eg, repeat prior dose or reduce dose) or temporarily hold therapy until ALT and AST return to baseline.

Adverse Reactions (Significant): Considerations

Hypersensitivity reaction

Life-threatening hypersensitivity reactions, including anaphylaxis and angioedema, have been reported in adult and pediatric patients treated with olipudase alfa. Infusion-related reaction (IRR; including acute phase reaction [APR]) has also been reported.

Mechanism: Non–dose-related; immunologic; IgE mediated (Ref).

Onset: Rapid; IgE-mediated reactions generally occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). IRRs typically occur within 12 to 72 hours postinfusion (Ref). In clinical trials, most APRs occurred 48 hours postinfusion during the dose escalation period.

Risk factors:

• Higher doses

• Rapid infusion rates

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and/or pediatrics.

>10%:

Cardiovascular: Hypotension, tachycardia

Dermatologic: Pruritus, skin rash, urticaria

Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting

Hematologic & oncologic: C-reactive protein increased

Hepatic: Increased serum transaminases

Hypersensitivity: Hypersensitivity reaction (including anaphylaxis and angioedema), infusion-related reaction (including acute phase reaction-like symptoms [including decreased serum iron; elevations of calcitonin and IL-6])

Local: Swelling at injection site

Nervous system: Fatigue, headache

Neuromuscular & skeletal: Arthralgia

Ophthalmic: Ocular hyperemia

Respiratory: Cough, pharyngeal edema, pharyngitis, rhinitis

Miscellaneous: Fever

1% to 10%:

Dermatologic: Erythema of skin, papule of skin

Nervous system: Asthenia

Neuromuscular & skeletal: Myalgia

Respiratory: Dyspnea, throat irritation

Frequency not defined: Immunologic: Antibody development

Contraindications

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

Warnings/Precautions

Concerns related to adverse effects:

• Elevated transaminases: May cause elevated ALT and/or AST within 24 to 48 hours following infusion; monitoring required. Elevated ALT and AST generally returned to preinfusion concentrations at the time of the next scheduled infusion.

Warnings: Additional Pediatric Considerations

Treatment-related serious adverse reactions, anaphylaxis, hypersensitivity reactions, and infusion-associated reactions occurred more often in pediatric patients as compared to adult patients. Pediatric patients were also more likely than adult patients to experience non-serious adverse reactions including fever, cough, rhinitis, urticaria, diarrhea, nausea, vomiting, and abdominal pain.

Dosage Forms: US

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

Solution Reconstituted, Intravenous [preservative free]:

Xenpozyme: Olipudase alfa-rpcp 4 mg (1 ea); Olipudase alfa-rpcp 20 mg (1 ea)

Generic Equivalent Available: US

Pricing: US

Solution (reconstituted) (Xenpozyme Intravenous)

4 mg (per each): $1,748.36

20 mg (per each): $8,741.81

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.

Administration: Pediatric

Note: Cardiopulmonary resuscitation equipment should be readily available during administration. Treatment should be in direct consultation with a physician knowledgeable in the management of acid sphingomyelinase deficiency (ASMD). Prior to administration, inspect for foaming; if foaming present, allow to dissipate prior to administration. Use an in-line low protein-binding 0.2 micron polyethersulfone or polytetrafluoroethylene filter and polyurethane or PVC DEHP-free infusion sets during administration.

Neonates, Infants, Children, and Adolescents <18 years: Infuse at rates described in the table, depending on olipudase alfa dose. Infusion rates are in mg per kg per hour.

**Olipudase Alfa Infusion Rate for Ages <18 Years**
Dose	Infusion rate
0.03 mg/kg	Infuse at 0.1 mg/kg/hour for the full length of the infusion.
0.1 mg/kg	Infuse at 0.1 mg/kg/hour for 20 minutes, then increase to 0.3 mg/kg/hour for the remainder of the infusion.
0.3 mg/kg	Infuse at 0.1 mg/kg/hour for 20 minutes, then increase to 0.3 mg/kg/hour for 20 minutes, then increase to 0.6 mg/kg/hour for the remainder of the infusion.
≥0.6 mg/kg	Infuse at 0.1 mg/kg/hour for 20 minutes, then increase to 0.3 mg/kg/hour for 20 minutes, then increase to 0.6 mg/kg/hour for 20 minutes, then increase to 1 mg/kg/hour for the remainder of the infusion.

Adolescents ≥18 years: Infuse at rates described in the table, depending on olipudase alfa dose. Infusion rates are in mL per hour.

**Olipudase Alfa Infusion Rate for Ages ≥18 Years**
Dose	Infusion rate
0.1 mg/kg	Infuse at 20 mL/hour for 20 minutes, then increase to 60 mL/hour for the remainder of the infusion.
≥0.3 mg/kg	Infuse at 3.3 mL/hour for 20 minutes, then increase to 10 mL/hour for 20 minutes, then increase to 20 mL/hour for 20 minutes, then increase to 33.33 mL/hour for the remainder of the infusion.

Maintenance doses may be infused at home in patients who tolerate their infusion well, based on physician evaluation and recommendation. Doses and infusion rates should remain constant and cannot be changed without physician supervision; if a dose is missed or delayed, contact physician.

Administration: Adult

IV: Cardiopulmonary resuscitation equipment should be readily available during administration. Treatment should be in direct consultation with a physician knowledgeable in the management of acid sphingomyelinase deficiency. Prior to administration, inspect for foaming; if foaming is present, allow to dissipate prior to administration. Use an inline, low protein-binding 0.2-micron filter during administration. Use polyurethane or PVC DEHP-free for infusion sets and polyethersulfone or polytetrafluoroethylene for inline filters. Use infusion rates as described below, starting with the rate listed under "Step 1." In the absence of infusion-associated reactions, increase infusion rate every 20 minutes sequentially through the remaining steps. At the end of the infusion, flush the infusion line with NS at the rate used for the last part of the infusion:

**Olipudase Alfa Infusion Rates**
Dose	Infusion rate
	Step 1 (20 minutes)	Step 2 (20 minutes)	Step 3 (20 minutes)	Step 4 (remainder of infusion time)
0.1 mg/kg	20 mL/hour	60 mL/hour	N/A	N/A
0.3 to 3 mg/kg	3.33 mL/hour	10 mL/hour	20 mL/hour	33.33 mL/hour

Hazardous Drugs Handling Considerations

This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Olipudase alfa may cause teratogenicity.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Storage/Stability

Store intact vials at 2°C to 8°C (36°F to 46°F). Do not freeze intact vials. After initial reconstitution with sterile water for injection, store at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at 20°C to 25°C (68°F to 77°F) for up to 6 hours (Note: Prior to March 2023, the manufacturer's labeling stated the reconstituted vials could be stored at room temperature for up to 12 hours). After further dilution with NS, store at 2°C to 8°C (36°F to 46°F) for up to 24 hours or at 20°C to 25°C (68°F to 77°F) for up to 12 hours (including infusion time). Do not freeze reconstituted or diluted solution.

Use

Treatment of non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) (FDA approved in all ages).

Metabolism/Transport Effects

None known.

Drug Interactions

There are no known significant interactions.

Reproductive Considerations

Verify pregnancy status prior to treatment initiation in patients who could become pregnant.

Patients who may become pregnant should use effective contraception during therapy and for 14 days after the last dose of olipudase.

Pregnancy Considerations

Based on data from animal reproduction studies with exposures less than the maximum recommended human dose, in utero exposure to olipudase may cause fetal harm.

Treatment with olipudase should not be initiated or escalated during pregnancy. The decision to continue treatment if pregnancy occurs during olipudase therapy should be individualized.

Monitoring Parameters

ALT and AST (baseline [within 1 month prior to treatment initiation], within 72 hours prior to each infusion during dose escalation phase, prior to the next scheduled dose following a missed dose, and then routinely during maintenance dosing as part of routine clinical management of acid sphingomyelinase deficiency); pregnancy test (baseline in people who can become pregnant). Monitor for hypersensitivity and infusion-associated reactions (eg, urticaria, erythema, headache, nausea, vomiting, fever).

Mechanism of Action

As an exogenous source of the enzyme acid sphingomyelinase (ASM), olipudase alfa degrades sphingomyelin to ceramide and phosphocholine. Olipudase alfa is not expected to cross the blood-brain-barrier or address CNS manifestations of ASM deficiency (ASMD).

Pharmacokinetics (Adult Data Unless Noted)

Note: Exposures are lower in pediatric patients compared with adults (Diaz 2021).

Distribution: 13 L.

Metabolism: Unknown; expected to be metabolized into small peptides and amino acids by catabolic pathways.

Half-life elimination: Adults: 32 to 38 hours.

<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi:10.1007/s40629-015-0052-6 [PubMed 26120552]
Diaz GA, Jones SA, Scarpa M, et al. One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. Genet Med. 2021;23(8):1543-1550. doi: 10.1038/s41436-021-01156-3 [PubMed 33875845]
US Department of Health and Human Services (HHS); Centers for Disease Control and Prevention (CDC); National Institute for Occupational Safety and Health (NIOSH). NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed September 2, 2022.
Wasserstein M, Lachmann R, Hollak C, et al. A randomized, placebo-controlled clinical trial evaluating olipudase alfa enzyme replacement therapy for chronic acid sphingomyelinase deficiency (ASMD) in adults: one-year results. Genet Med. 2022;24(7):1425-1436. doi:10.1016/j.gim.2022.03.021 [PubMed 35471153]
Xenopozyme (olipudase alfa) [prescribing information]. Cambridge, MA: Genzyme Corporation; December 2023.

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Olipudase alfa: Pediatric drug information