Laronidase (Aldurazyme) is a recombinant alpha-L-iduronidase enzyme that is responsible for the degradation of GAGs (Glycosaminoglycans) within the lysosomes.

Laronidase Uses:

• Mucopolysaccharidosis I (Hurler syndrome, Hurler-Scheie, and Scheie forms):

  • Used for treatment of Hurler and Hurler-Scheie forms of mucopolysaccharidosis I (MPS I); treatment of Scheie form of MPS I in patients with symptoms of moderate to severe intensity

Laronidase (Aldurazyme) Dose in Adults:

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

Laronidase (Aldurazyme) Dose in the treatment of MPS I (Hurler syndrome, Hurler-Scheie, and Scheie forms):

• IV: 0.58 mg/kg once a week; round up the dose to the nearest whole vial

Laronidase (Aldurazyme) Dose in Childrens:

Note: 1 hour prior to the start of infusion patient should be pre-medicated with antipyretics and/or antihistamines.

Laronidase (Aldurazyme) Dose in the treatment of Mucopolysaccharidosis I (Hurler syndrome, Hurler-Scheie, and Scheie forms):

• Infants ≥6 months, Children, and Adolescents:

  • IV: 0.58 mg/kg/dose once a week; round up the dose to the nearest whole vial

Pregnancy Risk Factor B

• There is limited information available about the pregnancy use of laronidase.
• Pregnant patients are encouraged to enroll in the MPS I registry (800-745-4447 or www.registrynxt.com).

Use during breastfeeding:

• It is not known if it is present in breast milk.
• There is limited information available about breastfeeding and laronidase.
• The manufacturer recommends caution when administering laronidase for nursing women. 
• Breastfeeding women are encouraged to enroll in the MPS I registry (800-7454447 or www.registrynxt.com).

Dose in Kidney Disease:

No dosage adjustments are provided in the manufacturer's labeling.

Dose in Liver disease:

No dosage adjustments are provided in the manufacturer's labeling.

Unless otherwise noted, adverse reactions were reported in patients more than six years of age.

Common Side Effects of Laronidase (Aldurazyme):

• Cardiovascular:

  • Flushing
  • Venous Irritation

• Central Nervous System:

  • Chills
  • Hyperreflexia
  • Paresthesia

• Dermatologic:

  • Skin Rash

• Immunologic:

  • Antibody Development

• Local:

  • Injection Site Reaction

• Otic:

  • Otitis Media

• Respiratory:

  • Upper Respiratory Tract Infection

• Miscellaneous:

  • Infusion-Related Reaction
  • Fever

Less Common Side Effects of Laronidase (Aldurazyme):

• Cardiovascular:

  • Hypertension
  • Oxygen Saturation Decreased
  • Tachycardia
  • Chest Pain
  • Edema
  • Facial Edema
  • Hypotension
  • Hot And Cold Flashes

• Central Nervous System:

  • Headache

• Dermatologic:

  • Pallor
  • Pruritus
  • Urticaria
  • Hyperhidrosis

• Gastrointestinal:

  • Abdominal Pain
  • Abdominal Distress
  • Diarrhea
  • Vomiting

• Hematologic & Oncologic:

  • Thrombocytopenia

• Hepatic:

  • Hyperbilirubinemia

• Hypersensitivity:

  • Severe Hypersensitivity

• Local:

  • Abscess At Injection Site
  • Pain At Injection Site

• Neuromuscular & Skeletal:

  • Tremor
  • Arthralgia
  • Back Pain
  • Musculoskeletal Pain

• Ophthalmic:

  • Corneal Opacity

• Respiratory:

  • Rales
  • Respiratory Distress
  • Wheezing
  • Bronchospasm
  • Cough
  • Dyspnea

Contraindications to Laronidase (Aldurazyme):

• The US labeling of the manufacturer does not contain any contraindications.

Canadian labeling:

• Hypersensitivity severe

Warnings and precautions

• Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]:

  • Infusion reactions can be severe. If you have hypersensitivity reactions, immediate treatment should be given.
  • Patients suffering from compromised pulmonary function and acute respiratory disease may need additional monitoring.
  • They may be at greater risk of acute exacerbation or worsening of their symptoms due to an infusion reaction.
  • The most common reactions are airway obstruction, bradycardia and bronchospasm as well as hypotension, hypoxia and hypotension. These can all occur within the first three hours after administration.
  • Infusions should be stopped immediately if severe reactions occur. During administration, medical assistance should be available.
  • After a severe hypersensitivity reaction, it is important to carefully weigh the risks and benefits of re-administration.
  • Patients who have severe reactions may need to be monitored for a longer time.
  • Consider caution when considering the use of epinephrine for anaphylaxis. Many patients with MPSI may already have a cardiac condition.

• Infusion reactions

  • Patients with acute febrile/respiratory illnesses should exercise caution and delay treatment as they may experience infusion-related reactions.
  • Pre-medicate with antipyretics or antihistamines.
  • Infusion reactions can be managed by reducing the rate of infusion, temporarily discontinuing infusions, and/or using additional antipyretics or antihistamines.

• Fluid overload:

  • Patients at high risk of fluid overload, or those with compromised cardiac and/or respiratory function should be cautious.
  • Extended observation may be required for some patients

• MPS-I

  • Patients with mild symptoms of the Scheie type of MPS-I have not been recommended for use.
  • It is not recommended for the CNS manifestations.

• Sleep Apnea

  • Patients with sleep apnea should not use it. Before initiating therapy, patients should be evaluated.
  • Infusions or the use of sedating Antihistamines should provide treatment options for apnea such as CPAP and supplemental oxygen.

Monitoring parameters:

• Vital signs
• FVC
• Height
• Weight
• Range of motion
• Serum antibodies to alpha-L-iduronidase
• Urine levels of glycosaminoglycans (GAG)
• Changes in liver size

How to administer Laronidase (Aldurazyme)?

IV:

• Use an infusion set with low protein-binding and 0.2-micrometer in-line filter for administration.
• Administer antipyretics and/or antihistamines 60 minutes prior to infusion.
• Volume and infusion rate are body weight-based; infusion should be delivered over almost 3 to 4 hours.
• An initial 10 mcg/kg/hour infusion rate may be increased incrementally every fifteen minutes during the 1st hour if tolerated (see below); the rate should be increased to a maximum infusion rate of 200 mcg/kg/hour which should be maintained for the rest of the infusion (~3 hours).
• If stable monitor vital signs every 15 minutes.
• Decrease the rate of infusion, temporarily discontinue the infusion, and/or administer additional antipyretics/antihistamines in case of infusion-related reaction in any patient.

The manufacturer has provided 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 the remainder of infusion (~3 hours)

Note: For patients with cardiac or respiratory compromise who weigh up to 30 kg, a total infusion volume of 100 mL Normal saline and slower infusion rate may be considered.

Mechanism of action of Laronidase (Aldurazyme):

• It is generated from Chinese hamster cells and is a recombinant form (replacement version) of alpha-Liduronidase. 
• Alpha-L-iduronidase, an enzyme that degrades endogenous glycosaminoglycans within lysosomes, is a lysosomal enzyme.
• A deficiency in alpha-Liduronidase can lead to accumulation of GAGs that cause cellular, tissue and organ dysfunction. 
• Patients with Hurler, Hurler Scheie, or Scheie have had their pulmonary function and walking ability improve by administering laronidase.

Half-life elimination:

• Infants and children 6 months to 5 Years: 0.3-1.9 Hours
• 1.5 to 3.6 hours for adults and children >= 6 years

Excretion

• Clearance for Infants and Children 6 Months to 5 Years: 2.2-7.7 ML/min/kilogram
• Clearance for children older than 6 years old and adults: Clearance: 1.7 to 2.7 mL/min/kilogram.
• The amount of antibodies that a patient develops against laronidase during the first 12 weeks of treatment will affect the rate at which the enzyme is cleared. 
• Clearance of laronidase is not affected by antibody titers if the treatment lasts for more than 26 weeks.

International Brand Names of Laronidase:

• Aldurazyme

Laronidase Brand Names in Pakistan:

No Brands Available in Pakistan.