Imiglucerase (Monograph)

Brand name: Cerezyme
Drug class: Enzymes
Chemical name: 495-L-Histidineglucosylceramidase (human placenta isoenzyme protein moiety)
Molecular formula: C₂₅₃₂H₃₈₄₃N₆₇₁O₇₁₁S₁₆
CAS number: 154248-97-2

Medically reviewed by Drugs.com on Mar 11, 2024. Written by ASHP.

Introduction

Biosynthetic (recombinant DNA origin) form of human β-glucocerebrosidase (glucosylceramidase).

Uses for Imiglucerase

Gaucher Disease

Long-term enzyme replacement therapy in patients with confirmed diagnosis of nonneuronopathic (type 1) Gaucher disease that results in one or more of the following conditions: anemia, thrombocytopenia, bone disease, hepatomegaly, or splenomegaly (designated an orphan drug by FDA for this use).

Role of imiglucerase therapy in patients with neuronopathic forms of Gaucher disease (type 2 or 3)^{† [off-label]} not established (designated an orphan drug by FDA for this use).

Imiglucerase Dosage and Administration

General

Individualize dosage and/or frequency of administration according to disease severity and individual requirements and response.

Administration

IV Administration

Administer by IV infusion.

May be administered using an inline, low protein-binding, 0.2-µm particulate filter as slight flocculation (evidenced by thin translucent fibers) may occasionally occur after dilution.

Reconstitution

Determine number of vials to be reconstituted based on patient weight.

Reconstitute appropriate number of vials containing 200 or 400 units of imiglucerase lyophilized powder with 5.1 or 10.2 mL of sterile water for injection, respectively, to provide a solution containing 40 units of imiglucerase per mL.

Dilution

Use strict aseptic technique since drug product contains no preservative.

Withdraw appropriate dose from reconstituted vials and dilute with 0.9% sodium chloride injection to a final volume of 100–200 mL.

Rate of Administration

Administer over 1–2 hours.

Dosage

Pediatric Patients

Gaucher Disease

IV

Children ≥2 years of age: Initially, dosage ranges from 2.5 units/kg 3 times weekly to 60 units/kg every 2 weeks.

Increase or decrease dosage and/or frequency of administration according to disease severity and patient response and convenience.

Individual doses occasionally may be increased or decreased slightly to avoid wasting a partially used vial, as long as the total monthly dosage is not altered substantially.

Clinical improvement in hematologic and visceral manifestations generally occurs within the first year of therapy; response to skeletal manifestations may require 2–3 years of therapy.

Failure to respond within 6 months may indicate the need for increased dosages.

Adults

Gaucher Disease

IV

Initially, dosage ranges from 2.5 units/kg 3 times weekly to 60 units/kg every 2 weeks.

Increase or decrease dosage and/or frequency of administration according to disease severity and patient response and convenience.

Individual doses occasionally may be increased or decreased slightly to avoid wasting a partially used vial, as long as the total monthly dosage is not altered substantially.

Clinical improvement in hematologic and visceral manifestations generally occurs within the first year of therapy; response to skeletal manifestations may require 2–3 years of therapy.

Failure to respond within 6 months may indicate the need for increased dosages.

Cautions for Imiglucerase

Contraindications

No known contraindications.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., pruritus, flushing, urticaria, angioedema, chest discomfort, dyspnea, coughing, cyanosis, hypotension) reported during or shortly after IV infusion; anaphylactoid reactions reported in <1% of patients.

Carefully reevaluate therapy if substantial clinical evidence of hypersensitivity develops. Use with caution in patients who have exhibited manifestations of hypersensitivity reactions. Further therapy can generally be administered successfully following a decrease in infusion rate and pretreatment with antihistamines and/or corticosteroids.

Antibody Formation

Potential for immunogenicity. Development of IgG antibodies to imiglucerase reported in approximately 15% of patients, usually within the first 6 months of therapy and rarely after 12 months of therapy. (See Distribution: Special Populations and Elimination: Special Populations under Pharmacokinetics.)

Possible increased risk of hypersensitivity reactions in patients with detectable IgG antibodies. (See Hypersensitivity Reactions under Cautions.) Use with caution in patients who have developed antibodies to the drug; monitor periodically for imiglucerase IgG antibodies during the first year of therapy.

Cross-hypersensitivity

Use with caution in patients previously treated with alglucerase who developed antibodies or exhibited hypersensitivity reactions to alglucerase.

General Precautions

Pulmonary Hypertension and Pneumonia

Pulmonary hypertension and pneumonia reported rarely; however, no causal relationship with the drug established.

Evaluate patients with respiratory symptoms in the absence of fever for the presence of pulmonary hypertension.

Specific Populations

Pregnancy

Category C.

Animal reproductive studies not conducted. Avoid use during pregnancy unless clearly needed and the potential benefits justify potential risks to fetus.

Lactation

Not known whether imiglucerase is distributed into milk. Use with caution.

Pediatric Use

Safety and efficacy not established in children <2 years of age, although the drug has been used in this age group.

Common Adverse Effects

Children 2–12 years of age: Dyspnea, fever, nausea, vomiting, flushing, coughing.

Adults and adolescents >12 years of age: Headache, pruritus, rash.

Imiglucerase Pharmacokinetics

Absorption

Onset

Steady-state enzymatic activity reached in 30 minutes during a 1-hour IV infusion.

Distribution

Extent

Volume of distribution ranges from 0.09–0.15 L/kg.

Special Populations

In patients who develop IgG antibodies, volume of distribution is decreased.

Elimination

Half-life

Following IV infusion, plasma enzymatic activity rapidly declines with a half-life of 3.6–10.4 minutes.

Special Populations

In patients who develop IgG antibodies, clearance is decreased and half-life is increased.

Stability

Storage

Parenteral

Powder for Injection

2–8°C.

Following reconstitution, stable at room temperature (25°C) and 2–8°C for up to 12 hours.

Following dilution, stable at 2–8°C for up to 24 hours.

Compatibility

Parenteral

Solution Compatibility1

Compatible
Sodium chloride 0.9%

Actions

Replaces the deficient endogenous enzyme β-glucocerebrosidase in patients with Gaucher disease.
Gaucher disease is an autosomal recessive lysosomal storage disorder characterized by a deficiency of the enzyme glucocerebrosidase, which results in accumulation of glucocerebroside within the lysosomes of macrophages in the liver, spleen, bone marrow, and other organs; clinical manifestations include hepatosplenomegaly, anemia, thrombocytopenia, and skeletal complications (e.g., osteopenia, osteonecrosis, progressive joint destruction, fractures).
Enzyme replacement therapy in patients with type 1 Gaucher disease increases the degradation of glucocerebroside to glucose and ceramide, with resultant reduction in liver and spleen size, amelioration of anemia and thrombocytopenia, decreased bone pain, decreased cachexia, and increased bone remineralization over a period of several years.

Advice to Patients

Risk of hypersensitivity reactions (pruritus, flushing, urticaria, angioedema, chest discomfort, dyspnea, coughing, cyanosis, hypotension).
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
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.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.