DrugindexOnline^{2nd edition}

Pronouncation: (ih-mih-GLUE-ser-ACE)
Class: Enzyme replacement

Trade Names:
Cerezyme
- Powder for injection, lyophilized 212 units
- Powder for injection, lyophilized 424 units

Mechanism of Action

Pharmacology

Imiglucerase catalyzes the hydrolysis of glucocerebroside to glucose and ceramide.

Pharmacokinetics

Distribution

Vd is 0.09 to 0.15 L/kg. Steady state achieved by 30 min during 1 h infusion.

Elimination

The t _½ is 3.6 to 10.4 min. Plasma Cl ranges from 9.8 to 20.3 mL/min/kg.

Indications and Usage

Long-term enzyme replacement therapy for pediatric and adult patients with confirmed diagnosis of Type I Gaucher disease that results in at least 1 of the following conditions: anemia, bone disease, hepatomegaly, splenomegaly, or thrombocytopenia.

Contraindications

Standard considerations.

Dosage and Administration

Adults and children older than 2 yr of age

IV Dosage is individualized. Initial dose ranges from 2.5 units/kg 3 times/wk to 60 units/kg once every 2 wk. Dosage adjustments should be made based on achievement of therapeutic goals as assessed by routine comprehensive evaluations of the patient's clinical manifestations.

General Advice

• For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
• Reconstitute powder for injection with sterile water for injection: 5.1 mL for 200 unit vial; 10.2 mL for 400 unit vial.
• Do not use if reconstituted solution is cloudy, discolored, or contains opaque particles. Slight flocculation (thin translucent fibers) may be noted.
• Vials contain no preservative and, after reconstitution, should be promptly diluted. Discard any unused reconstituted solution. Do not save for future use.
• Withdraw prescribed dose of imiglucerase from vials and dilute with sodium chloride 0.9% injection to final volume of 100 to 200 mL.
• Administer diluted solution by IV infusion over 1 to 2 h.
• Diluted solution may be filtered through an in-line, low protein-binding 0.2 mcm filter during administration.
• Consider pretreatment with antihistamines and/or corticosteroids and reduction in rate of infusion if hypersensitivity symptoms developed during previous infusion.

Storage/Stability

Store vials in refrigerator (36° to 46°F). Reconstituted solution is stable for up to 12 h when stored in refrigerator or at room temperature not exceeding 77°F. Diluted solution is stable for up to 24 h if refrigerated.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Tachycardia (6%).

CNS

Dizziness, fatigue, headache (6%).

Dermatologic

Rash (6%); flushing, pruritus (postmarketing).

GI

Abdominal pain, diarrhea, nausea, vomiting (6%).

Hypersensitivity

Hypersensitivity symptoms, including angioedema, chest discomfort, coughing, cyanosis, dyspnea, flushing, hypotension, pruritus, urticaria (6%); anaphylactoid reaction (less than 2%).

Musculoskeletal

Backache (6%).

Respiratory

Coughing, dyspnea (postmarketing).

Miscellaneous

Chills (6%); fever (postmarketing).

Precautions

Monitor Periodically monitor for immunoglobulin G (IgG) antibody formation during first year of treatment.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy established in patients between 2 and 16 yr of age. Safety and efficacy in patients less than 2 yr of age not established.

Hypersensitivity

Use with caution in patients who have exhibited symptoms of hypersensitivity to imiglucerase. Anaphylactoid reactions have been reported but most patients successfully continued treatment after reduction in infusion rate and pretreatment with antihistamines and/or corticosteroids.

Immunogenicity

IgG antibodies to imiglucerase developed in 15% of treated patients during first year of therapy, most within 6 mo of treatment and rarely after 12 mo. Approximately 46% of patients with detectable IgG antibodies experienced hypersensitivity symptoms.

Physician use

Imiglucerase should be used only by health care professionals knowledgeable in the management of patients with Gaucher disease.

Previous treatment with alglucerase

Use with caution in patients who developed antibodies or symptoms of hypersensitivity during previous treatment with alglucerase.

Pulmonary hypertension/pneumonia

Pulmonary hypertension and pneumonia have been observed in less than 1% of treated patients, but a relationship with imiglucerase has not been established. Evaluate patients with respiratory symptoms in absence of fever for presence of pulmonary hypertension.

Overdosage

Symptoms

No reports of obvious toxicity at doses up to 240 units/kg every 2 wk.

Patient Information

• Advise patient or caregiver that medication will be prepared and administered by a health care provider in a health care setting.
• Advise patient or caregiver that reactions during or shortly after infusion of imiglucerase occur commonly and that medications may be given before the infusion in an effort to prevent or reduce the severity of these reactions.
• Advise patient or caregiver to notify health care provider if any of the following occur: pain, redness, or burning at infusion site; persistent or intolerable nausea, vomiting, stomach pain, diarrhea, or dizziness; any other unexplained symptom or sign.