Laronidase

Medically reviewed by Drugs.com. Last updated on Sep 6, 2020.

• Overview
• Side Effects
• Dosage
• Professional
• Interactions
• More

Pronunciation

(lair OH ni days)

Index Terms

• Recombinant α-L-Iduronidase (Glycosaminoglycan α-L-Iduronohydrolase)

Dosage Forms

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

Solution, Intravenous [preservative free]:

Aldurazyme: 2.9 mg/5 mL (5 mL) [contains polysorbate 80]

Brand Names: U.S.

• Aldurazyme

Pharmacologic Category

• Enzyme

Pharmacology

Laronidase is a recombinant (replacement) form of alpha-L-iduronidase derived from Chinese hamster cells. Alpha-L-iduronidase is an enzyme needed to break down endogenous glycosaminoglycans (GAGs) within lysosomes. A deficiency of alpha-L-iduronidase leads to an accumulation of GAGs, causing cellular, tissue, and organ dysfunction as seen in MPS I. Improved pulmonary function and walking capacity have been demonstrated with the administration of laronidase to patients with Hurler, Hurler-Scheie, or Scheie (with moderate-to-severe symptoms) forms of MPS.

Distribution

Infants and Children 6 months to 5 years: V_d: 0.12-0.56 L/kg

Children ≥6 years and Adults: V_d: 0.24-0.6 L/kg

Excretion

Infants and Children 6 months to 5 years: Clearance: 2.2-7.7 mL/minute/kg

Children ≥6 years and Adults: Clearance: 1.7-2.7 mL/minute/kg; during the first 12 weeks of therapy the clearance of laronidase increases proportionally to the amount of antibodies a given patient develops against the enzyme. However, with long-term use (≥26 weeks) antibody titers have no effect on laronidase clearance.

Half-Life Elimination

Infants and Children 6 months to 5 years: 0.3-1.9 hours

Children ≥6 years and Adults: 1.5-3.6 hours

Use: Labeled Indications

Mucopolysaccharidosis I (Hurler syndrome, Hurler-Scheie, and Scheie forms): Treatment of Hurler and Hurler-Scheie forms of mucopolysaccharidosis I (MPS I); treatment of Scheie form of MPS I in patients with moderate to severe symptoms

Contraindications

There are no contraindications listed within the manufacturer’s US labeling.

Canadian labeling: Severe hypersensitivity to laronidase or any component of the formulation

Dosing: Adult

Note: Premedicate with antipyretic and/or antihistamines 1 hour prior to start of infusion.

MPS I (Hurler syndrome, Hurler-Scheie, and Scheie forms): IV: 0.58 mg/kg once weekly; dose should be rounded up to the nearest whole vial

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Premedicate with antipyretic and/or antihistamines 1 hour prior to start of infusion.

Mucopolysaccharidosis I (Hurler syndrome, Hurler-Scheie, and Scheie forms): Infants ≥6 months, Children, and Adolescents: IV: 0.58 mg/kg/dose once weekly; dose should be rounded up to the nearest whole vial

Reconstitution

Determine the number of vials to dilute by calculating the required dose and rounding up to the nearest whole vial. Allow vials to come to room temperature prior to admixture. Do not use if the solution is discolored or contains particulate matter. Prepare the infusion using a low protein-binding container (there is no compatibility information of diluted laronidase in glass containers). Total volume of infusion is determined by body weight. For patients weighing ≤20 kg (or weighing up to 30 kg and with cardiac or respiratory compromise), dilute the required dose in 100 mL NS; for patients weighing >20 kg, dilute required dose in 250 mL NS. Remove and discard a volume of NS from the infusion bag equal to the volume of the calculated dose of laronidase. Slowly withdraw from vial(s) and slowly add laronidase to the NS; avoid excessive agitation; do not use filter needle. Gently rotate infusion bag to mix (do not shake).

Administration

IV: Administer using an infusion set with low protein-binding and 0.2 micrometer in-line filter. Antipyretics and/or antihistamines should be administered 60 minutes prior to infusion. Volume and infusion rate are based on body weight; deliver infusion over ~3 to 4 hours. An initial 10 mcg/kg/hour infusion rate may be incrementally increased every 15 minutes during the first hour if tolerated (see below); increase to a maximum infusion rate of 200 mcg/kg/hour which is maintained for the remainder of the infusion (~3 hours). Vital signs should be monitored every 15 minutes, if stable; in case of infusion-related reaction in any patient, decrease the rate of infusion, temporarily discontinue the infusion, and/or administer additional antipyretics/antihistamines. Manufacturer provides the following infusion rate information for patients receiving usual preparation:

≤20 kg: Total infusion volume: 100 mL

2 mL/hour for 15 minutes

4 mL/hour for 15 minutes

8 mL/hour for 15 minutes

16 mL/hour for 15 minutes

32 mL/hour for remainder of infusion (~3 hours)

>20 kg: Total infusion volume: 250 mL

5 mL/hour for 15 minutes

10 mL/hour for 15 minutes

20 mL/hour for 15 minutes

40 mL/hour for 15 minutes

80 mL/hour for remainder of infusion (~3 hours)

Note: A total infusion volume of 100 mL NS and slower infusion rate may be considered for patients with cardiac or respiratory compromise who weigh up to 30 kg.

Storage

Store vials under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Do not shake. Following dilution in NS, solution for infusion should be used immediately; however, if not used immediately, diluted solutions should be refrigerated at 2°C to 8°C (36°F to 46°F) for up to 36 hours.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Unless otherwise noted, adverse reactions were reported in patients ≥6 years of age.

>10%:

Cardiovascular: Flushing (23%)

Dermatologic: Skin rash (5% to 36%, including infants and children 6 months to 5 years of age)

Immunologic: Antibody development (93% to 100%, including infants and children 6 months to 5 years of age)

Local: Injection site reaction (18%)

Nervous system: Chills (infants and children 6 months to 5 years of age: 20%), hyperreflexia (14%), paresthesia (14%)

Otic: Otitis media (infants and children 6 months to 5 years of age: 20%)

Respiratory: Upper respiratory tract infection (32%)

Miscellaneous: Fever (infants and children 6 months to 5 years of age: 30%); infusion-related reaction (32% to 35%, includes; infants and children 6 months to 5 years of age)

1% to 10%:

Cardiovascular: Chest pain (9%), edema (9%), facial edema (9%), hypotension (9%), increased blood pressure (infants and children 6 months to 5 years of age: 10%), oxygen saturation decreased (infants and children 6 months to 5 years of age: 10%), tachycardia (infants and children 6 months to 5 years of age: 10%)

Dermatologic: Pallor (infants and children 6 months to 5 years of age), pruritus (infants and children 6 months to 5 years of age)

Hematologic & oncologic: Thrombocytopenia (9%)

Hepatic: Hyperbilirubinemia (9%)

Hypersensitivity: Severe hypersensitivity, severe infusion-related reaction

Infection: Abscess (9%)

Local: Pain at injection site (9%)

Neuromuscular & skeletal: Tremor (infants and children 6 months to 5 years of age)

Ophthalmic: Corneal opacity (9%)

Respiratory: Rales (infants and children 6 months to 5 years of age), respiratory distress (infants and children 6 months to 5 years of age), wheezing (infants and children 6 months to 5 years of age)

Frequency not defined: Hypersensitivity: Angioedema

Postmarketing:

Cardiovascular: Peripheral edema

Dermatologic: Erythema of skin

Hypersensitivity: Anaphylactic shock, anaphylaxis

Nervous system: Fatigue

Respiratory: Cyanosis, laryngeal edema

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]: Anaphylactic reactions have been observed during infusion, immediate treatment for hypersensitivity reactions should be available during administration. Additional monitoring may be required in patients with compromised respiratory function or acute respiratory disease; may be at increased risk for acute exacerbation of respiratory symptoms due to infusion reaction. Reactions, which may include airway obstruction, bradycardia, bronchospasm, hypotension, hypoxia, respiratory distress/failure, stridor, tachypnea, and urticaria, may be severe and tend to occur during or within 3 hours after administration. Immediately discontinue infusion if severe reactions occur; medical support should be available during administration. Risks and benefits should be carefully considered prior to readministration following a severe hypersensitivity reaction. Patients who initially experience severe reactions may require prolonged monitoring. In the case of anaphylaxis, caution should be used if epinephrine is being considered; many patients with MPS I have pre-existing heart disease.

• Infusion reactions: Infusion reactions may occur; use caution and consider delaying treatment in patients with acute febrile/respiratory illness; may result in increased risk for infusion-related reactions. Pretreatment with antipyretics and antihistamines is recommended. Decrease infusion rate, temporarily discontinue infusion, and/or administer additional antipyretics and antihistamines to manage infusion reactions.

Disease-related concerns:

• Fluid overload: Use with caution in patients at risk for fluid overload or in conditions where fluid restriction is indicated (eg, acute underlying respiratory illness, compromised cardiac and/or respiratory function); conditions may be exacerbated during infusion. Extended observation may be necessary for some patients.

• MPS I: Appropriate use: Has not been studied in patients with mild symptoms of the Scheie form of MPS I. Not indicated for the CNS manifestations of the disorder.

• Sleep apnea: Use with caution in patients with sleep apnea; evaluate patients prior to initiation of therapy. Apnea treatment options should be readily available (eg, CPAP or supplemental oxygen) during infusion or with use of sedating antihistamines.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

• Registry: A patient registry has been established and all patients are encouraged to participate. Registry information may be obtained at www.registrynxt.com or by calling 1-800-745-4447.

Monitoring Parameters

Vital signs, FVC, height, weight, range of motion, serum antibodies to alpha-L-iduronidase, urine levels of glycosaminoglycans (GAG), change in liver size

Pregnancy Considerations

Information related to the use of laronidase in pregnancy is limited (Anbu 2006; Castorina 2015).

Pregnant patients are encouraged to enroll in the mucopolysaccharidosis I registry (1-800-745-4447, extension 15500 or www.registrynxt.com).

Patient Education

What is this drug used for?

• It is used to treat mucopolysaccharidosis I.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Flushing

• Warm sensation

• Cold sensation

• Sweating a lot

• Common cold symptoms

• Injection site irritation

• Abdominal pain

• Nausea

• Vomiting

• Back pain

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse

• Severe headache

• Pale skin

• Tremors

• Twitching

• Chest pain

• Fast heartbeat

• Slow heartbeat

• Severe dizziness

• Passing out

• Chills

• Burning or numbness feeling

• Bruising

• Bleeding

• Swelling

• Vision changes

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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