Aldurazyme

Generic Name: Laronidase
Class: Enzymes
ATC Class: A16AB05
VA Class: RE900
Chemical Name: α-l-[8-Histidine] (human) iduronidase
Molecular Formula: C3567H5645N921O1261S12P4
CAS Number: 210589-09-6

Introduction

Biosynthetic (recombinant DNA origin) replacement form of l-iduronidase.1 3 4

Uses for Aldurazyme

Mucopolysaccharidosis I

Replacement therapy in patients with Hurler’s or Hurler-Scheie forms of mucopolysaccharidosis I (MPS I),2 3 as well as in patients with Scheie’s form of MPS I2 who have moderate to severe symptoms1 (designated an orphan drug by FDA for this use).4

Slideshow: Prescription Drug Addiction - Are You at Risk?

Risks and benefits of laronidase therapy in mildly affected patients with Scheie’s syndrome not established.1

Aldurazyme Dosage and Administration

General

  • To minimize the risk of infusion-related reactions, administer antipyretics and/or antihistamines 60 minutes prior to each infusion.1

  • Infusion should be slowed or temporarily discontinued and appropriate supportive treatment initiated if signs or symptoms of an infusion reaction occur. 1 (See Infusion Reactions under Cautions.)

Administration

IV Administration

Administer by IV infusion.1

Laronidase injection concentrate contains no preservative; vials are for single use only.1

Do not mix with other drugs in the same infusion solution.1

Laronidase solutions should be prepared using PVC containers and administered with a PVC infusion set equipped with an inline, low-protein-binding filter with a pore diameter of 0.2 mcm.1

Dilution

Use strict aseptic technique since drug product contains no preservative.a

Laronidase vials should be allowed to reach room temperature before dilution; do not heat (e.g., in a microwave).1

Determine appropriate number of vials to be diluted based on patient’s body weight and recommended dosage.1

Patients weighing ≤20 kg should receive a total infusion volume of 100 mL; patients weighing >20 kg should receive a total infusion volume of 250 mL.1

Laronidase injection concentrate must be diluted in 0.9% sodium chloride containing 0.1% albumin human prior to administration.1

Prepare infusion bag of 0.9% sodium chloride containing albumin human 0.1% based on the total infusion volume.1 Remove and discard the volume of 0.9% sodium chloride equal to the volume of albumin human to be added (see Table 1).1 Add appropriate volume of albumin human to the infusion bag; gently rotate to ensure proper distribution of the albumin.1

Table 1. Preparation of 0.9% Sodium Chloride Containing Albumin Human 0.1% Infusion Solution1

Total Infusion Volume

Volume of Albumin Human 5% to be Added to Infusion Bag

Volume of Albumin Human 25% to be Added to Infusion Bag

100 mL

2 mL

0.4 mL

250 mL

5 mL

1 mL

Prior to addition of calculated volume of laronidase injection concentrate to infusion bag, remove and discard an equal volume of 0.9% sodium chloride containing albumin human 0.1%.1 Slowly withdraw the calculated volume of laronidase injection concentrate from the appropriate number of vials and add slowly to the infusion bag; gently rotate bag.1 Do not use a filter needle, since it may cause agitation, which may denature laronidase and render the drug biologically inactive.1

Rate of Administration

Administer total volume of the infusion over 3–4 hours.1

Initially, infuse at a rate of 10 mcg/kg per hour; rate may be increased incrementally every 15 minutes during the first hour of the infusion, as tolerated, up to a maximum rate of 200 mcg/kg per hour.1 Maximum rate should be continued for the remainder of the infusion (2–3 hours).1

Recommended infusion protocols are summarized in Table 2 and Table 3.a

Monitor patient’s vital signs; if stable at the end of the 15-minute infusion time, increase infusion rate to the next recommended level.

Table 2. Infusion Protocol for Patients Weighing ≤20 kg (Total Volume of Infusion 100 mL)a

Infusion Rate

Duration of Infusion

Initially, 2 mL per hour (10 mcg/kg per hour)

15 minutes

4 mL per hour (20 mcg/kg per hour)

15 minutes

8 mL per hour (50 mcg/kg per hour)

15 minutes

16 mL per hour (100 mcg/kg per hour)

15 minutes

32 mL per hour (200 mcg/kg per hour)

For remainder of inufsion (approximately 3 hours)

Monitor patient’s vital signs; if stable at the end of the 15-minute infusion time, increase infusion rate to the next recommended level.a

Table 3. Infusion Protocol for Patients Weighing >20 kg (Total Volume of Infusion 250 mL)a

Infusion Rate

Duration of Infusion

Initially, 5 mL per hour (10 mcg/kg per hour)

15 minutes

10 mL per hour (20 mcg/kg per hour)

15 minutes

20 mL per hour (50 mcg/kg per hour)

15 minutes

40 mL per hour (100 mcg/kg per hour)

15 minutes

80 mL per hour (200 mcg/kg per hour)

For remainder of infusion (approximately 3 hours)

Dosage

Dosage of laronidase is expressed in mg.1 The specific activity of laronidase is 172 units/mg.1

Pediatric Patients

Mucopolysaccharidosis I
IV

Children ≥5 years of age: 0.58 mg/kg administered once weekly.1

Adults

Mucopolysaccharidosis I
IV

0.58 mg/kg administered once weekly.1

Cautions for Aldurazyme

Contraindications

  • No known contraindications.1

Warnings/Precautions

Sensitivity Reactions

Infusion Reactions

Risk of potentially severe infusion reactions consistent with hypersensitivity reactions.a

Signs and symptoms include flushing, fever, headache, rash, cough, bronchospasm, dyspnea, urticaria, angioedema, and pruritus.1 Severe reactions, including anaphylaxis requiring emergency tracheostomy, also reported.1

Administer antipyretics and/or antihistamines prior to infusion.1 (See General under Dosage and Administration.) Infusion reactions may be controlled by slowing the infusion rate or administering appropriate treatment (additional antipyretics and/or antihistamines).1

If severe hypersensitivity or anaphylactic reaction occurs, discontinue immediately and institute appropriate therapy as indicated.1 Administer subsequent infusions with extreme caution, considering risks and benefits of therapy, and with appropriate resuscitation measures available.a

Caution advised if epinephrine is considered for use in patients with MPS I because of the increased prevalence of CAD in such patients.1

General Precautions

MPS I Registry

A registry has been established to monitor the variability and progression of MPS I disease and to monitor and evaluate treatments for the disease.a Information is available at and 800-745-4447.a

Immunogenicity

Antibodies to laronidase develop in most patients;1 clinical importance, including potential for drug neutralization, not known.1

Development of laronidase-specific IgE binding antibodies and complement activation reported in a patient with an anaphylactic reaction to larondiase.a (See Infusion Reactions under Cautions.)

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether laronidase is distributed into milk.1 Caution advised if laronidase is used. 1 Register nursing women at 800-745-4447 or .1

Pediatric Use

Safety and efficacy not established in children <5 years of age.1

Geriatric Use

Safety and/or efficacy in those ≥65 years of age not studied specifically to date;1 it is not known whether geriatric patients respond differently than younger patients.1

Common Adverse Effects

Rash, upper respiratory tract infection, injection site reactions, infusion-related reactions (flushing, fever, headache, and rash).1

Interactions for Aldurazyme

No formal drug interaction studies to date.1

Aldurazyme Pharmacokinetics

Distribution

Extent

Not known whether laronidase crosses the blood-brain barrier or distributes into milk.a

Elimination

Half-life

1.5–3.6 hours.1

Stability

Storage

Parenteral

Powder for Injection

2–8°C; do not freeze or shake.1

Following dilution, 2–8°C for up to 36 hours; however, immediate use following dilution is preferred since product contains no preservatives.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible

Sodium Chloride 0.9%

Drug Compatibility
Admixture Compatibility

Compatible

Albumin 0.1%

Actions

  • Biosynthetic (recombinant DNA origin) replacement form of l-iduronidase, a lysosomal enzyme that catalyzes the hydrolysis of terminal α-l-iduronic acid residues of dermatan sulfate and heparan sulfate.1 3 4

  • Provides an exogenous source of l-iduronidase for uptake into lysosomes and catabolism of glycosaminoglycans.1

Advice to Patients

  • Importance of notifying clinician immediately if manifestations of infusion reaction (fever, flushing, headache, rash, cough, difficulty breathing) occur.b

  • Importance of informing patients that a registry has been established to monitor the variability and progression of MPS I and to evaluate treatments for the disease; importance of encouraging patient participation and of advising patients that participation may involve long-term follow-up.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and herbal products.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Laronidase (Recombinant DNA Origin)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, concentrate, for IV infusion only

0.58 mg/mL (2.9 mg)

Aldurazyme (preservative-free)

Genzyme

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. BioMarin Pharmaceutical Inc. Aldurazyme (laronidase) for intravenous infusion prescribing information. Novato, CA. 2003 Apr

2. Kakkis ED, Muenzer J, Tiller GE et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med. 2001; 344:182-8. [IDIS 458270] [PubMed 11172140]

3. Anon. Laronidase. BioDrugs. 2002; 16:316-8. [PubMed 12196045]

4. US Food and Drug Administration. FDA approves first treatment for genetic metabolic disorder including Hurler disorder. Rockville, MD; 2003 Apr 30. FDA Talk Paper. No. T03-32.

5. Kakkis ED, McEntee MF, Schmidtchen A et al. Long-term and high-dose trials of enzyme replacement therapy in the canine model of mucopolysaccharidosis I. Biochem Mol Med. 1996; 58:156-67. [PubMed 8812735]

6. Grabowski GA. Lysosomal storage diseases. In: Braunwald E, Fauci AS, , Kasper DL et al, eds. Harrison’s principles of internal medicine. l5th ed. New York: McGraw Hill Company; 2001: 2276-81.

7. Peters C, Shapiro EG, Anderson J et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. Blood. 1998; 91:2601-8. [PubMed 9516162]

8. Grewal SS, Krivit W, Defor TE et al. Outcome of second hematopoietic cell transplantation in Hurler syndrome. Bone Marrow Transplant. 2002; 29:491-6. [IDIS 479500] [PubMed 11960268]

9. Genzyme Corporation. Mucopolysaccharidosis I and Aldurazyme (laronidase). Cambridge, MA; 2003 Apr. Press release from website .

10. Genzyme Corporation, Cambridge, MA: Personal communication.

a. Genzyme Corporation. Aldurazyme (laronidase) solution for intravenous infusion prescribing information. Cambridge, MA. 2005 May.

b. Genzyme Corporation. Aldurazyme (laronidase) solution for intravenous infusion patient information. Cambridge, MA. 2003 May.

Hide
(web3)