Aldurazyme^® (Concentrate) Instructions for Use

Marketing Authorization Holder

Sanofi, B.V. (Netherlands)

Manufactured By

Vetter Pharma-Fertigung, GmbH & Co. KG (Germany)

Packaging and Quality Control Release

EUROAPI UK, Limited (United Kingdom)

ATC Code

A16AB05 (Laronidase)

Active Substance

Laronidase (Rec.INN registered by WHO)

Dosage Form

Aldurazyme®

Concentrate for solution for infusion 100 IU/1 ml: vial 5 ml 1, 10 or 25 pcs.

Dosage Form, Packaging, and Composition

5 ml – vials (1) – cardboard packs.
5 ml – vials (10) – cardboard packs.
5 ml – vials (25) – cardboard packs.

Clinical-Pharmacological Group

Drug for the treatment of hereditary enzymatic deficiency

Pharmacotherapeutic Group

Alimentary tract and metabolism – enzymes

Pharmacological Action

Recombinant human alpha-L-iduronidase, produced by recombinant DNA technology from a Chinese hamster ovary cell line. It is a lysosomal hydrolase. It causes hydrolysis of the acid residues of the glycosaminoglycans (mucopolysaccharides) heparan sulfate and dermatan sulfate. The predicted amino acid sequence of the recombinant form, as well as the nucleotide sequence that encodes it, are identical to the polymorphic form of human alpha-L-iduronidase.

The ability of laronidase to cross the blood-brain barrier has not been evaluated in experimental and clinical studies.

Indications

Mucopolysaccharidosis type I (Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome /moderate and severe forms/).

ICD codes

Dosage Regimen

Administer Aldurazyme^® as an intravenous infusion. Calculate the dosage based on patient body weight.

The recommended dosage is 0.58 mg per kilogram of body weight, administered once weekly.

Reconstitute each vial with 5.3 ml of Water for Injections to yield a final concentration of 0.58 mg/ml (100 IU/ml). Gently swirl the vial; do not shake or invert. Inspect the solution for particulate matter and discoloration prior to administration.

Dilute the calculated volume of reconstituted solution in 0.9% Sodium Chloride intravenous solution. Use a final infusion volume of 100 ml for patients weighing less than 20 kg and 250 ml for patients weighing 20 kg or more.

Administer the diluted solution using a non-pyrogenic, low-protein binding infusion set with an in-line, low-protein binding 0.2 μm filter.

Initiate the infusion at a rate of 2 mcg/kg/hour (approximately 3.5 IU/kg/hour). If well tolerated, the infusion rate may be increased in a step-wise manner every 15 minutes, as tolerated, to a maximum rate of 43 mcg/kg/hour (approximately 74 IU/kg/hour).

The total infusion time is typically 3 to 4 hours. Do not infuse as an intravenous push or bolus.

Premedicate with antihistamines and/or antipyretics approximately 60 minutes prior to the start of the infusion. Monitor patients closely during and for an appropriate period after administration for signs of infusion-associated reactions.

Adverse Reactions

The most serious side effects identified in clinical and post-marketing studies are anaphylactic and allergic reactions.

In clinical studies with laronidase, the most frequently reported events were upper respiratory tract infections, rash, and reactions at the injection site.

Clinical studies also reported infusion-associated reactions, among which the most frequently reported were flushing, fever, rash, and headache, less frequently – cough, bronchospasm, dyspnea, urticaria, angioedema, pruritus.

Post-marketing studies have also reported the following adverse reactions: fever, nausea, vomiting, arthralgia, diarrhea, tachycardia, abdominal pain, increased blood pressure, decreased oxygen saturation.

The majority of patients receiving laronidase therapy developed antibodies to laronidase. The clinical significance of this effect is unknown.

The following effects were reported in placebo-controlled studies: upper respiratory tract infections, chest pain, hyperreflexia, paresthesia, skin rash, abscess, bilirubinemia, hypotension, thrombocytopenia, pain and reactions at the injection site, venous complications, congestive edema, corneal opacity.

Contraindications

No contraindications have been established.

Use in Pregnancy and Lactation

No well-controlled and adequate studies on the use of laronidase in pregnant women have been conducted to date.

It is not known whether Laronidase is excreted in breast milk.

Experimental studies have not revealed impairment of fertility or damaging effects on the fetus. Studies of the mutagenic and carcinogenic potential of laronidase have not been conducted.

Special Precautions

Life-threatening anaphylactic reactions (respiratory failure, respiratory distress syndrome, stridor, tachypnea, bronchospasm, airway obstruction, hypoxia, bradycardia, urticaria) may develop during the infusion of laronidase or within 3 hours after it. Antihistamines and antipyretics should be administered prior to infusion, and medical supervision and monitoring of the patient should be provided.

Drug Interactions

No drug interactions have been established.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.