Laronidase (Monograph)

Brand name: Aldurazyme
Drug class: Enzymes

Medically reviewed by Drugs.com on Jul 10, 2025. Written by ASHP.

Warning

Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available.
Discontinue laronidase immediately and initiate appropriate medical treatment if a severe hypersensitivity reaction occurs.
Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions and require additional monitoring.

Introduction

Biosynthetic (recombinant DNA origin) replacement form of l-iduronidase.

Uses for Laronidase

Mucopolysaccharidosis I

Replacement therapy in adult and pediatric patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I), as well as in patients with the Scheie form of MPS I who have moderate to severe symptoms (designated an orphan drug by FDA for this use).

Efficacy and safety of laronidase in mildly affected patients with the Scheie form not established.

Effect of laronidase on CNS manifestations of the disorder has not been determined.

Approved therapeutic options for MPS I include hematopoietic stem cell transplantation and/or enzyme replacement therapy (i.e., laronidase). Treatment should begin as early as possible; however, effects appear to wear off after several years.

Laronidase Dosage and Administration

General

Premedication and Prophylaxis

Consider premedication with antihistamines, with or without antipyretics, 60 minutes before initiation of the laronidase infusion.

Dispensing and Administration Precautions

Administer laronidase with appropriate medical monitoring and support measures readily available.

Administration

IV Administration

Administer by IV infusion.

If ≥1 doses of laronidase are missed, restart therapy as soon as possible with maintenance of the 1-week interval between infusions thereafter. Do not double a dose to compensate for a missed dose.

Dilution

Prepare laronidase solutions using low-protein-binding containers and administer with infusion set equipped with an inline, low-protein-binding filter with a pore diameter of 0.2 µm. The commercially available injection concentrate must be diluted in 0.9% sodium chloride prior to administration to a final volume of 50 mL, 100 mL, or 250 mL as determined by patient's weight and cardiopulmonary condition.

Patients weighing ≥2 kg and <4 kg should receive a total volume of 50 mL. Patients weighing ≥4 kg and up to 20 kg should receive a total volume of 100 mL. Patients weighing >20 kg should receive a total volume of 250 mL. For patients weighing up to 30 kg with underlying cardiac or respiratory compromise, consider a total volume of 100 mL administered at a reduced infusion rate.

Remove appropriate number of laronidase vials from refrigerator and allow to reach room temperature (20–25ºC) before dilution; do not heat vials (e.g., in a microwave). Inspect vials visually for particulate matter and discoloration prior to dilution and administration; solution should be clear to slightly opalescent and colorless to pale yellow. Discard if concentrate is discolored or if visible particulate matter is present.

Withdraw volume of 0.9% sodium chloride from appropriate infusion bag, equal to the volume of laronidase to be added. Slowly add calculated volume of laronidase from appropriate number of vials into infusion bag. Avoid excessive agitation. Discard any unused solution. Gently rotate infusion bag; do not shake.

Infuse solution within 8 hours after removal from refrigeration, including the total infusion time. Do not infuse in the same IV line with other products.

Rate of Administration

Initial infusion rate of 10 mcg/kg per hour is recommended; rate may be increased every 15 minutes during first hour of infusion, as tolerated, up to a maximum rate of 200 mcg/kg per hour (see Table 1). Continue maximum rate for remainder of infusion (2–3 hours for a total infusion time of approximately 3 to 4 hours).

Upon completion of infusion, flush the line with 0.9% sodium chloride, using same infusion rate as the one used for the last part of infusion.

Dosage

Dosage of laronidase is expressed in mg. The specific activity of laronidase is 172 units/mg.

Pediatric Patients

Mucopolysaccharidosis I

IV

0.58 mg/kg (actual body weight) administered by infusion once weekly.

Adults

Mucopolysaccharidosis I

IV

0.58 mg/kg (actual body weight) administered by infusion once weekly.

Modifications due to Hypersensitivity or Infusion-associated Reactions

If a mild to moderate hypersensitivity reaction occurs, consider temporarily withholding infusion for 15 to 30 minutes, or slowing infusion rate by 25 to 50%, and initiating appropriate medical treatment. Halt infusion and monitor patient if symptoms persist despite withholding infusion or slowing infusion rate. May reinitiate infusion within 7 to 14 days using incremental rate steps in Table 1, up to 25 or 50% of the infusion rate at which the reaction occurred with appropriate premedication.

Resume infusion rate at a 25 to 50% reduced rate as tolerated if symptoms subsided after withholding the infusion. Alternatively, if symptoms subside after slowing infusion rate, complete infusion at the reduced rate as tolerated. Beginning with the next infusion, increase infusion rate by increments of 25% as tolerated until recommended infusion rate is reached and closely monitor the patient.

If a severe hypersensitivity or infusion-related reaction occurs, immediately discontinue infusion and initiate appropriate medical treatment.

Table 1. Incremental Infusion Rate Steps and Volumes for Laronidase Infusion by Patient Weight.1
Patient Weight Range (kg)	Total Infusion Volume (mL)	Step 1 10 mcg/kg/hour	Step 2 20 mcg/kg/hour	Step 3 50 mcg/kg/hour	Step 4 100 mcg/kg/hour	Step 5 200 mcg/kg/hour
		Infusion Rate	Infusion Rate	Infusion Rate	Infusion Rate	Infusion Rate
≥2 to <4	50	1 mL/hour	2 mL/hour	4 mL/hour	8 mL/hour	16 mL/hour
≥4 to <20	100	2 mL/hour	4 mL/hour	8 mL/hour	16 mL/hour	32 mL/hour
≥20	250	5 mL/hour	10 mL/hour	20 mL/hour	40 mL/hour	80 mL/hour

Special Populations

Manufacturer states no special dosage recommendations for geriatric patients or those with hepatic or renal impairment.

Cautions for Laronidase

Contraindications

None.

Warnings/Precautions

Warnings

Hypersensitivity Reactions Including Anaphylaxis

Hypersensitivity reactions, including anaphylaxis, reported in patients during or up to 3 hours after completion of laronidase IV infusions (see Boxed Warning). Some reactions were life-threatening with symptoms potentially including respiratory failure, respiratory distress, stridor, tachypnea, bronchospasm, obstructive airway disorder, hypoxia, hypotension, bradycardia, and urticaria. Pre-existing upper airway obstruction may have contributed to the severity of some reactions in patients with MPS I.

Consider premedication with antihistamines, with or without antipyretics, 60 minutes prior to initiation of infusion. Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available. Recurrent reactions are possible; some patients may require prolonged observation.

If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, immediately discontinue therapy and initiate appropriate medical treatment. In patients with MPS I there is an increased prevalence of coronary artery disease; therefore, exercise caution if epinephrine is being considered for use. Interventions for severe hypersensitivity reactions have included resuscitation, mechanical ventilatory support, emergency tracheotomy, hospitalization, and treatment with inhaled beta-adrenergic agonists, epinephrine, and IV corticosteroids.

Consider risks and benefits of readministration following severe hypersensitivity reactions. Rechallenge using slower infusion rates may occur; desensitization procedures may also be considered. If readministration is undertaken, ensure patient tolerates infusion. Infusion rate may be increased to recommended rate if patient tolerates infusion. If a mild or moderate hypersensitivity reaction occurs, consider temporarily holding infusion or slowing infusion rate.

Acute Respiratory Complications Associated with Administration

Risk of infusion reactions may be elevated in patients with an acute febrile or respiratory illness at time of laronidase infusion (see Boxed Warning). Consider patient’s clinical status prior to laronidase infusion and a delay in therapy if necessary.

Perform an evaluation of airway patency prior to laronidase administration as sleep apnea is common in MPS I patients. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an infusion reaction, or extreme drowsiness/sleep induced by antihistamine use.

Other Warnings/Precautions

Acute Cardiorespiratory Failure

In postmarketing, acute cardiorespiratory failure reported. Patients at an increased risk of serious exacerbation of cardiac or respiratory status during infusions include those susceptible to fluid overload, or those with an acute underlying respiratory illness or compromised cardiac and/or respiratory function for whom fluid restriction is indicated. Consider administration of a decreased total infusion volume and infusion rate to these patients. Additionally, appropriate medical monitoring and support measures should be readily available; some patients may require prolonged observation times.

Infusion-associated Reactions

Infusion-associated reactions may occur. Consider premedication with antihistamines, with or without antipyretics, 60 minutes prior to initiation in order to reduce, but not eliminate, the risk of infusion-associated reactions. Discontinue laronidase immediately and initiate appropriate medical treatment if a severe infusion-associated reaction occurs. After considering risks and benefits of readministration following a severe reaction, may rechallenge patients using slower infusion rates. May increase infusion rate to the recommended rate if patient tolerates infusion. If a mild or moderate infusion-associated reaction occurs, consider temporarily holding infusion or slowing infusion rate.

Immunogenicity

In clinical studies, 70 (96%)of 73 laronidase-treated patients developed IgG anti-drug antibodies (ADAs). The onset of ADA positivity occurred within 2 months after starting therapy in most patients. ADA titers peaked at approximately 4 months and generally declined over time, with higher titers seen in patients with Hurler forms of MPS I. Neutralizing antibodies that inhibited cellular laronidase uptake were detected in 38 (54%) of the 70 patients with ADAs. Neutralizing antibodies that inhibited laronidase enzyme activity were found in a single patient with ADAs.

Specific Populations

Pregnancy

No drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes was identified in pregnant women from clinical data within the MPS I Registry pregnancy sub-registry, published case reports, and a global pharmacovigilance database. The decision to continue laronidase therapy during pregnancy should be individualized.

Pregnant women with MPS I and clinicians are encouraged to enroll in the MPS I pregnancy sub-registry by calling 1-800-745-4447 ext. 15500 or visiting [Web].

Lactation

Clinical data insufficient to evaluate presence or absence of laronidase in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for laronidase and any potential adverse effects on the breastfed child from the drug or the underlying maternal condition.

Lactating women with MPS I and clinicians are encouraged to enroll in the MPS I Registry by calling 1-800-745-4447 ext. 15500 or visiting [Web].

Pediatric Use

Safety and efficacy established in pediatric patients with Hurler and Hurler-Scheie forms of MPS I and pediatric patients with Scheie form of MPS I who have moderate to severe symptoms. Safety and efficacy of laronidase in pediatric patients 6 months to 5 years of age were found to be similar to pediatric patients 6–18 years of age and adults for these indications.

Geriatric Use

Patients ≥65 years of age not included in clinical studies of laronidase to determine if these patients respond differently than younger patients.

Common Adverse Effects

Most common adverse effects reported in ≥10% of patients ≥6 months of age include infusion reactions (e.g., pyrexia, chills, increased blood pressure, tachycardia, and decreased oxygen saturation).

Most common adverse effects reported in ≥10% of patients ≥6 years of age include rash, upper respiratory tract infection, injection site reaction, hyperreflexia, paresthesia, flushing, poor venous access.

Drug Interactions

No formal drug interaction studies to date.

Laronidase Pharmacokinetics

Distribution

Extent

Not known whether laronidase distributes into human milk.

Elimination

Half-life

1.5–3.6 hours.

Stability

Storage

Parenteral

Powder for Injection

2–8°C; do not freeze or shake.

Following dilution, 2–8°C for up to 36 hours; however, immediate use following dilution is preferred since product contains no preservatives.

Actions

Biosynthetic (recombinant DNA origin) replacement form of l-iduronidase, a lysosomal enzyme that catalyzes the hydrolysis of terminal α-l-iduronic acid residues of dermatan sulfate and heparan sulfate.
Provides an exogenous source of l-iduronidase for uptake into lysosomes and catabolism of glycosaminoglycans.

Advice to Patients

Advise patients that hypersensitivity and infusion-associated reactions may occur during and up to 3 hours after laronidase treatment. Inform patients of the signs and symptoms of these reactions and to immediately seek medical care if these occur.
Advise patients to report immediately to a clinician if signs or symptoms of cardiac or respiratory decompensation occur during or following an infusion. Inform patients who use supplemental oxygen or continuous positive airway pressure (CPAP) during sleep to have these treatments readily available during therapy.
Inform patients that a registry has been established to monitor the variability and progression of MPS I and to evaluate treatments for the disease; stress importance of encouraging patient participation and advise patients that participation may involve long-term follow-up.
Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and herbal products.
Advise patients to inform clinicians if they are or plan to become pregnant or to breast-feed. Encourage patients to contact the MPS I registry if pregnant or breastfeeding while receiving therapy.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.