Laronidase is a medication used to treat a rare genetic disorder known as Mucopolysaccharidosis I (MPS I), specifically the Hurler and Hurler-Scheie forms of the disease. MPS I is an inherited metabolic disorder in which the body is unable to break down certain complex carbohydrates called glycosaminoglycans (GAGs) due to a deficiency of the enzyme alpha-L-iduronidase.

Laronidase is a recombinant human enzyme replacement therapy (ERT) that provides the missing enzyme alpha-L-iduronidase. By administering Laronidase intravenously, it helps to break down and metabolize the accumulated GAGs in various tissues and organs, slowing the progression of the disease and improving some of the associated symptoms.

A recombinant alpha-L-iduronidase enzyme called laronidase (Aldurazyme) is in charge of breaking down GAGs (Glycosaminoglycans) inside lysosomes.

Uses:

• Hurler syndrome, Hurler-Scheie, and Scheie variants of mucopolysaccharidosis I:
  • used to treat MPS I individuals with symptoms of moderate to severe severity who have the Scheie form of MPS I as well as people with the Hurler and Hurler-Scheie types of MPS I.

Laronidase (Aldurazyme) Dose in Adults:

Antipyretic and/or antihistamines should be taken 1 hour before the infusion begins.

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

• To treat this condition, the medicine is given as an injection into the vein (intravenously).
• The amount of medicine you get depends on your weight.
• It's about 0.58 milligrams for every kilogram you weigh.
• And they round up the dose to the nearest whole vial, which is a container for the medicine.
• This treatment is usually given once a week to help manage the condition.

Laronidase (Aldurazyme) Dose in Children:

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

Therapy of mucopolysaccharidosis type I (Hurler syndrome, Hurler-Scheie, and Scheie forms) with laronidase (Aldurazyme) dosage:

For infants who are at least 6 months old, children, and adolescents, the typical dose of Laronidase is given as an injection into a vein (IV).

• The dose is about 0.58 milligrams for every kilogram of the person's body weight, and it's administered once a week.
• To make it easier to measure and administer, the dose is rounded up to the nearest whole vial, which is a container for the medication.
• This treatment is used to help manage the condition.

Pregnancy Risk Factor B

• The use of laronidase during pregnancy is not well-studied, and there is limited information available regarding its safety and potential risks.

Use during breastfeeding:

• The presence of laronidase in breast milk is not well-established, and there is limited information available regarding its use in breastfeeding women.
• Therefore, caution is advised when considering the use of laronidase in nursing women.
• Women who are nursing are recommended to sign up for the MPS I register (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.

Negative side effects were documented in patients older than six years old, unless otherwise stated.

Common Side Effects of Laronidase (Aldurazyme):

• Local:
  • Injection Site Reaction
• Cardiovascular:
  • Flushing
  • Venous Irritation
• Dermatologic:
  • Skin Rash
• Respiratory:
  • Upper Respiratory Tract Infection
• Central Nervous System:
  • Paresthesia
  • Chills
  • Hyperreflexia
• Immunologic:
  • Antibody Development
• Otic:
  • Otitis Media
• Miscellaneous:
  • Fever
  • Infusion-Related Reaction

Less Common Side Effects of Laronidase (Aldurazyme):

• Central Nervous System:
  • Headache
• Hypersensitivity:
  • Severe Hypersensitivity
• Cardiovascular:
  • Chest Pain
  • Edema
  • Facial Edema
  • Hypertension
  • Oxygen Saturation Decreased
  • Tachycardia
  • Hypotension
  • Hot And Cold Flashes
• Gastrointestinal:
  • Diarrhea
  • Vomiting
  • Abdominal Pain
  • Abdominal Distress
• Hematologic & Oncologic:
  • Thrombocytopenia
• Dermatologic:
  • Pallor
  • Hyperhidrosis
  • Pruritus
  • Urticaria
• Hepatic:
  • Hyperbilirubinemia
• Local:
  • Abscess At Injection Site
  • Pain At Injection Site
• Ophthalmic:
  • Corneal Opacity
• Neuromuscular & Skeletal:
  • Tremor
  • Musculoskeletal Pain
  • Arthralgia
  • Back Pain
• Respiratory:
  • Wheezing
  • Bronchospasm
  • Cough
  • Rales
  • Respiratory Distress
  • Dyspnea

Contraindications to Laronidase (Aldurazyme):

In the United States, the manufacturer's labeling for laronidase does not list any specific contraindications, meaning there are no absolute reasons to avoid its use in terms of specified conditions or factors.

In the Canadian labeling, laronidase is contraindicated for individuals who have a severe hypersensitivity (allergic reaction) to laronidase or any component of the formulation. This contraindication is a clear warning against using laronidase in individuals with a known severe allergy to the medication or any of its ingredients.

Warnings and precautions

Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]:

• Laronidase can cause severe allergic reactions during infusion, which may include problems with breathing, slow heart rate, difficulty breathing, low blood pressure, lack of oxygen, breathing difficulties or failure, noisy breathing, fast breathing, and hives.
• These reactions can be serious and often happen during or within 3 hours after the medicine is given.
• If these severe reactions occur, the infusion should be stopped right away, and medical help should be available during the treatment.
• It's essential to think carefully about the risks and benefits before giving the medicine again to someone who had a severe allergic reaction.
• Patients who had severe reactions may need close monitoring.
• If there's a need for epinephrine (a treatment for severe allergic reactions), caution should be used because many patients with MPS I already have heart problems.

Infusion reactions

• Sometimes, when giving laronidase through an infusion, there can be infusion reactions.
• These reactions might be more likely in patients who have a current fever or respiratory illness.
• To lower the risk of these reactions, it's a good idea to give the patient fever and allergy medicines before the infusion.
• If there's an infusion reaction, the rate of the infusion can be slowed down, or the infusion can be temporarily stopped.
• You can also provide more fever and allergy medicines to manage these reactions.
• So, it's important to be careful and prepared when giving laronidase through an infusion.

Fluid overload:

• Be careful when using laronidase in patients who might already have too much fluid in their bodies or when they need to limit their fluid intake (like if they have a serious respiratory problem or heart and lung issues).
• Giving laronidase could make these conditions worse during the infusion.
• Some patients may need to be watched for a longer time to make sure they are okay after getting the medicine.
• So, it's important to consider these factors and be cautious when using laronidase in such cases.

MPS-I

• Laronidase, used to treat MPS I, hasn't been studied in people with mild symptoms of the Scheie form of the disorder.
• It's also not meant for treating the symptoms that affect the central nervous system (CNS).
• This means it's mainly for specific forms of MPS I and other aspects of the condition, not for milder cases or for problems in the central nervous system.
• The use of laronidase should be guided by the specific symptoms and form of MPS I in each patient.

Sleep Apnea

• When using laronidase, be cautious in patients who have sleep apnea.
• Before starting treatment, it's a good idea to check if a patient has sleep apnea.
• If they do, you should have treatments available for apnea (like a CPAP machine or extra oxygen) in case they are needed during the infusion.
• Also, be careful when using sedating antihistamines with these patients.
• It's important to ensure their safety and well-being during treatment.

Monitoring parameters:

Vital Signs:

• Keep an eye on the patient's heart rate, blood pressure, and body temperature throughout treatment.

FVC (Forced Vital Capacity):

• Measure how much air the patient can exhale forcefully. This helps assess lung function.

Height and Weight:

• Track changes in the patient's height and weight to monitor growth and nutrition.

Range of Motion:

• Check the patient's ability to move their joints to ensure they're not getting stiff.

Serum Antibodies to Alpha-L-Iduronidase:

• Monitor the levels of antibodies in the blood to see how the body is responding to treatment.

Urine Levels of Glycosaminoglycans (GAG):

• Measure the GAG levels in urine to assess the impact of treatment on the disease.

Change in Liver Size:

• Keep an eye on the size of the liver as it may change during treatment.

How to administer Laronidase (Aldurazyme)?

• Infusion Set: Use an infusion set with low protein-binding and a 0.2 micrometer in-line filter.
• Pre-Medication: Administer antipyretics and/or antihistamines 60 minutes before the infusion to reduce the risk of reactions.
• Infusion Duration: The infusion should take approximately 3 to 4 hours.
• Infusion Rate: Start with an initial rate of 10 mcg/kg/hour. You can gradually increase it every 15 minutes during the first hour if it's well tolerated. The maximum infusion rate is 200 mcg/kg/hour, which should be maintained for the rest of the infusion.
• Monitoring: Check vital signs every 15 minutes. If they remain stable, continue the infusion. In case of an infusion-related reaction, you may need to slow down the infusion rate, temporarily stop the infusion, or give more antipyretics and antihistamines.

Infusion Rate Information for Patients Receiving Usual Preparation:

For patients weighing ≤20 kg:

• Total infusion volume: 100 mL
• Start at 2 mL/hour for 15 minutes
• Then increase gradually:
  • 4 mL/hour for 15 minutes
  • 8 mL/hour for 15 minutes
  • 16 mL/hour for 15 minutes
  • 32 mL/hour for the rest of the infusion (~3 hours)

For patients weighing >20 kg:

• Total infusion volume: 250 mL
• Start at 5 mL/hour for 15 minutes
• Then increase gradually:
  • 10 mL/hour for 15 minutes
  • 20 mL/hour for 15 minutes
  • 40 mL/hour for 15 minutes
  • 80 mL/hour for the rest of the infusion (~3 hours)

Note: In patients with cardiac or respiratory issues weighing up to 30 kg, consider using a total infusion volume of 100 mL of normal saline (NS) and a slower infusion rate.

Mechanism of action of Laronidase (Aldurazyme):

• Laronidase is a man-made version of a natural enzyme called alpha-L-iduronidase, which comes from Chinese hamster cells.
• This enzyme is crucial for breaking down certain substances called glycosaminoglycans (GAGs) in our cells.
• When there's not enough of this enzyme, as in the case of MPS I (a genetic disorder), GAGs build up in the body and cause problems in cells, tissues, and organs.
• By giving laronidase to patients with severe forms of MPS I (like Hurler, Hurler-Scheie, or Scheie), it has been shown to improve lung function and the ability to walk.
• This treatment helps manage the disease's symptoms and reduce its impact on the body.

Distribution:

• Infants and Children (6 months to 5 years): Volume of distribution is approximately 0.12-0.56 liters per kilogram of body weight.
• Children (≥6 years) and Adults: Volume of distribution is about 0.24-0.6 liters per kilogram of body weight.

Half-life Elimination:

• Infants and Children (6 months to 5 years): Laronidase has an elimination half-life ranging from 0.3 to 1.9 hours in this age group.
• Children (≥6 years) and Adults: In older children and adults, the elimination half-life falls within the range of 1.5 to 3.6 hours.

Excretion:

• Infants and Children (6 months to 5 years): The clearance rate of laronidase in this age group ranges from 2.2 to 7.7 milliliters per minute per kilogram of body weight.
• Children (≥6 years) and Adults: In older children and adults, the clearance rate is approximately 1.7 to 2.7 milliliters per minute per kilogram of body weight. It's worth noting that during the first 12 weeks of therapy, laronidase clearance increases in proportion to the amount of antibodies the patient develops against the enzyme. However, with long-term use (≥26 weeks), antibody levels do not affect laronidase clearance.

International Brand Names of Laronidase:

• Aldurazyme

Laronidase Brand Names in Pakistan:

Not Available.