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Laronidase

FDA Drug Information • Also known as: Aldurazyme

Brand Names
Aldurazyme
Drug Class
Hydrolytic Lysosomal Glycosaminoglycan-specific Enzyme [EPC]
Route
INTRAVENOUS
Dosage Form
INJECTION, SOLUTION, CONCENTRATE
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS, and ACUTE RESPIRATORY COMPLICATIONS ASSOCIATED WITH ADMINISTRATION WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS, and ACUTE RESPIRATORY COMPLICATIONS ASSOCIATED WITH ADMINISTRATION See full prescribing information for complete boxed warning . Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available. If a severe hypersensitivity reaction occurs, discontinue ALDURAZYME immediately and initiate appropriate medical treatment. ( 5.1 ) 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. Appropriate respiratory support should be available during infusion. ( 5.2 ) Hypersensitivity Reactions Including Anaphylaxis Patients treated with ALDURAZYME have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during ALDURAZYME administration. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue ALDURAZYME immediately and initiate appropriate medical treatment. In patients with severe hypersensitivity reactions, a desensitization procedure to ALDURAZYME may be considered [see Warnings and Precautions (5.1) ] . Acute Respiratory Complications Associated with Administration 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 [see Warnings and Precautions (5.2) ] .

Description

11 DESCRIPTION ALDURAZYME (laronidase) is a polymorphic variant of the human enzyme α-L-iduronidase that is produced by recombinant DNA technology in a Chinese hamster ovary cell line. α-L-iduronidase (glycosaminoglycan α-L-iduronohydrolase, EC 3.2.1.76) is a lysosomal hydrolase that catalyzes the hydrolysis of terminal α-L-iduronic acid residues of dermatan sulfate and heparan sulfate. Laronidase is a glycoprotein with a molecular weight of approximately 83 kD. The predicted amino acid sequence of the recombinant form, as well as the nucleotide sequence that encodes it, are identical to a polymorphic form of human α-L-iduronidase. The recombinant protein is comprised of 628 amino acids after cleavage of the N-terminus and contains 6 N-linked oligosaccharide modification sites. Two oligosaccharide chains terminate in mannose-6-phosphate sugars. ALDURAZYME has a specific activity of approximately 172 U/mg. ALDURAZYME, for intravenous infusion, is supplied as a sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted prior to administration in 0.9% Sodium Chloride Injection, USP. The solution in each vial contains a nominal laronidase concentration of 0.58 mg/mL and a pH of approximately 5.5. The extractable volume of 5 mL from each vial provides 2.9 mg laronidase, 43.9 mg sodium chloride, 63.5 mg sodium phosphate monobasic monohydrate, 10.7 mg sodium phosphate dibasic heptahydrate, and 0.05 mg polysorbate 80. ALDURAZYME does not contain preservatives; vials are for single dose only.

What Is Laronidase Used For?

1 INDICATIONS AND USAGE ALDURAZYME ® is indicated for the treatment of: adult and pediatric patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I) and patients with the Scheie form of MPS I who have moderate to severe symptoms. ALDURAZYME is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme indicated for the treatment of adult and pediatric patients with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I) and for the treatment of patients with the Scheie form of MPS I who have moderate to severe symptoms. ( 1 ) Limitations of Use: The risks and benefits of treating mildly affected patients with the Scheie form have not been established. ( 1 ) ALDURAZYME has not been evaluated for effects on the central nervous system manifestations of the disorder. ( 1 ) Limitations of Use The safety and effectiveness of treating mildly affected patients with the Scheie form have not been established. The effect of ALDURAZYME on central nervous system manifestations of the disorder has not been determined.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For pretreatment recommendations, see Full Prescribing Information. ( 2.1 ) The recommended dosage is 0.58 mg/kg administered once weekly as an intravenous infusion. ( 2.2 ) For dosage and administration modifications due to hypersensitivity reactions or infusion-associated reactions (IARs), see Full Prescribing Information. ( 2.3 ) For instructions on preparation, storage, and administration, see Full Prescribing Information. ( 2.4 , 2.5 , 2.6 ) 2.1 Recommendations Prior to ALDURAZYME Treatment Premedication Prior to ALDURAZYME administration, consider premedicating with antihistamines, with or without antipyretics, 60 minutes before the start of infusion [see Warnings and Precautions (5.1 , 5.4) ]. Medical Support Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during ALDURAZYME administration. 2.2 Recommended Dosage and Administration The recommended dosage of ALDURAZYME is 0.58 mg/kg (actual body weight) administered once weekly as an intravenous infusion. ALDURAZYME injection must be diluted with 0.9% Sodium Chloride Injection to a final volume of 50 mL, 100 mL or 250 mL as determined by the patient's body weight and cardiopulmonary condition: Patients with a body weight equal to or greater than 2 kg and less than 4 kg should receive a total volume of 50 mL; patients with a body weight equal to or greater than 4 kg and up to 20 kg should receive a total volume of 100 mL; and those patients with a body weight greater than 20 kg should receive a total volume of 250 mL [see Dosage and Administration (2.6) ]. For patients with underlying cardiac or respiratory compromise and weighing up to 30 kg, physicians may consider diluting ALDURAZYME in a volume of 100 mL and administering at a decreased infusion rate [see Dosage and Administration (2.6) ]. The initial infusion rate of ALDURAZYME is 10 mcg/kg/hr and may be increased every 15 minutes during the first hour, as tolerated, to a maximum infusion rate of 200 mcg/kg/hr. The maximum rate is then maintained for the remainder of the infusion (2 to 3 hours) [see Dosage and Administration (2.6) , Warnings and Precautions (5.2 , 5.3) ] . If one or more doses are missed, restart ALDURAZYME treatment as soon as possible and maintain the 1-week interval between infusions thereafter. Do not double a dose to compensate for a missed dose. 2.3 Administration Modifications due to Hypersensitivity or Infusion Associated Reaction In the event of a severe hypersensitivity reaction (e.g. anaphylaxis) or severe infusion-associated reaction (IAR), immediately discontinue ALDURAZYME administration and initiate appropriate medical treatment. For additional recommendations in the event of a severe hypersensitivity reaction, [ see Warnings and Precautions (5.1) ]. In the event of a mild to moderate hypersensitivity reaction or a mild to moderate IAR, consider temporarily holding the infusion for 15 to 30...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Serious and or clinically significant adverse reactions described elsewhere in labeling include: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] Acute Respiratory Complications Associated with Administration [see Warnings and Precautions (5.2) ] Acute Cardiorespiratory Failure [see Warnings and Precautions (5.3) ] Infusion-Associated Reactions [see Warnings and Precautions (5.4) ] Most common adverse reactions (≥10%) in patients: 6 months of age and older are: infusion reactions (pyrexia, chills, blood pressure increased, tachycardia, and oxygen saturation decreased). ( 6.1 ) 6 years and older are: rash, upper respiratory tract infection, injection site reaction, hyperreflexia, paresthesia, flushing, and poor venous access. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme at 1-800-745-4447 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Serious adverse reactions reported with ALDURAZYME treatment during clinical trials were anaphylactic and hypersensitivity reactions. The most common adverse reactions were infusion reactions. The frequency of infusion reactions decreased over time with continued use of ALDURAZYME, and the majority of reactions were classified as being mild to moderate in severity. Clinical Trials in Patients 6 Years and Older A 26-week, double-blind, placebo-controlled clinical study (Study 1) of ALDURAZYME was conducted in 45 patients with MPS I, ages 6 to 43 years old, gender evenly distributed (N=23 females and 22 males). Of these 45 patients, 1 was clinically assessed as having Hurler form, 37 Hurler-Scheie, and 7 Scheie. Patients were randomized to receive either 0.58 mg/kg intravenously of ALDURAZYME per week for 26 weeks or placebo. All patients were treated with antipyretics and antihistamines prior to the infusions. Infusion reactions were reported in 32% (7 of 22) of ALDURAZYME-treated patients. The most common adverse reactions reported in patients who received ALDURAZYME were flushing, pyrexia, headache, and rash. Flushing occurred in 5 patients (23%) receiving ALDURAZYME; the other reactions were less frequent. Less common infusion reactions included angioedema (including face edema), hypotension, paresthesia, feeling hot, hyperhidrosis, tachycardia, vomiting, back pain, and cough. Other reported adverse reactions included bronchospasm, dyspnea, urticaria and pruritus. Table 2 enumerates adverse reactions and selected laboratory abnormalities that occurred during the 26-week placebo-controlled study (Study 1) that were reported in at least 2 patients more in the ALDURAZYME group than in the placebo group. Table 2: Adverse Reactions that Occurred in at Least 2 Patients More in the ALDURAZYME Group than in the Placebo Group Among Adult and Pediatric Patients with MPS I in Study 1 ALDURAZYME N=22 n (%) Placebo N=23 n (%) Blood and lymphatic system disorders Thrombocytopenia 2 (9) 0 Eye disorders Corneal opacity 2 (9) 0 General disorders and administration site conditions Chest pain 2 (9) 0 Face edema 2 (9) 0 Gravitational edema 2 (9) 0 Injection site pain 2 (9) 0 Injection site reaction 4 (18) 2 (9) Hepatobiliary disorders Hyperbilirubinemia 2 (9) 0 Infections and infestations Abscess 2 (9) 0 Upper respiratory tract infection 7 (32) 4 (17) Nervous system disorders Hyperreflexia 3 (14) 0 Paresthesia 3 (14) 1 (4) Skin and subcutaneous tissue disorders Rash 8 (36) 5 (22) Vascular disorders Hypotension 2 (9) 0 Poor venous access 3 (14) 0 All 45 patients who completed the placebo-controlled study (Study 1) continued treatment in an open-label, uncontrolled extension study (Study 2). All patients received ALDURAZYME 0.58 mg/kg of...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Exposure Registry An MPS I Registry has been established. Pregnant women with MPS I and healthcare providers are encouraged to contact the pregnancy sub-registry by visiting www.registrynxt.com or calling 1-800-745-4447 ext. 15500. Risk Summary Available data from the MPS I Registry pregnancy sub-registry, published case reports, and the global pharmacovigilance database with ALDURAZYME use in more than 30 pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The continuation of treatment for MPS I during pregnancy should be individualized to the pregnant woman. Untreated MPS I may result in adverse pregnancy and infant outcomes ( see Clinical Considerations ). No evidence of fetal harm has been observed in rats when laronidase was administered during organogenesis at doses up to 6.2 times the recommended human dose (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo-Fetal Risk Pregnancy can exacerbate preexisting clinical manifestations of MPS and lead to adverse pregnancy outcomes for both mother and fetus. Data Animal Data When laronidase was administered to pregnant female rats during organogenesis (gestation days [GD] 7-17) at doses of 0, 0.036, 0.36 or 3.6 mg/kg/day intravenously (equivalent to 7.3, 73.1, 730.8 units/kg/day) decreased maternal body weight gains and food consumption were observed with no corresponding effects on reproductive and litter parameters including number and distribution of corpora lutea, implantations and early and late resorptions at doses up...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING ALDURAZYME (laronidase) injection is supplied as a colorless to pale yellow, clear to slightly opalescent solution in single-dose, clear Type I glass vial. Each vial contains 2.9 mg/5 mL (0.58 mg/mL) of laronidase. The closure consists of a siliconized butyl stopper and an aluminum seal with a plastic flip-off cap. ALDURAZYME is available as: One single-dose vial in a carton (NDC 58468-0070-1) Refrigerate vials of ALDURAZYME at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light. This product contains no preservatives.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.