Pill Identifier App

Imiglucerase (Systemic)


VA CLASSIFICATION
Primary: HS451

Commonly used brand name(s): Cerezyme.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Enzyme (glucocerebrosidase) replenisher—

Indications

Accepted

Gaucher's disease, (treatment)—Imiglucerase is indicated as enzyme replacement therapy in Type I Gaucher's disease, in which glucocerebrosidase is deficient, resulting in an accumulation of glycolipids in the spleen, liver, and bone marrow. Clinical manifestations requiring treatment include moderate to severe anemia, thrombocytopenia with bleeding tendency, bone disease, and/or significant hepatomegaly or splenomegaly. {01} {02}


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Imiglucerase catalyzes the hydrolysis of the glycolipid, glucocerebroside, to glucose and ceramide as part of the normal degradation pathway for membrane lipids. {01}

Distribution:

Vol D—0.09 to 0.15 L per kg of body weight. {01}

Half-life:

Elimination—3.6 to 10.4 minutes. {01}

Time to peak effect:

During one-hour intravenous infusions of four doses (7.5, 15, 30, 60 Units per kg of body weight) steady-state enzymatic activity was achieved by 30 minutes. {01}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to alglucerase may be sensitive to imiglucerase also. {01}

Carcinogenicity/Mutagenicity

Carcinogenicity and mutagenicity studies have not been performed in either animals or humans.

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans.

Studies have not been done in animals. {01}

FDA Pregnancy Category C. {01}

Breast-feeding

It is not known whether imiglucerase is distributed into breast milk. {01}

Pediatrics

Appropriate studies on the relationship of age to the effects of imiglucerase have not been performed in the pediatric population. However, pediatrics-specific problems that would limit the usefulness of this medication in children are not expected. {09}


Geriatrics


No information is available on the relationship of age to the effects of imiglucerase in geriatric patients.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Sensitivity to alglucerase or imiglucerase{01}
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Acid phosphatase, serum or{02}
Angiotensin-converting enzymes, serum{02}{10}    (determinations recommended every 2 to 3 months by some clinicians; values should decrease with imiglucerase treatment {03} {05} {06} {09})


Alanine aminotransferase (ALT [SGPT]) and{16}
Aspartate aminotransferase (AST [SGOT]){16}    (some clinicians recommend monitoring every 6 to 12 months; {13} values should decrease during imiglucerase therapy)


Bilirubin concentrations, serum{15} and
Calcium, serum and{15}
Creatinine, serum and{15}
Electrolyte concentrations, serum and{15}
Phosphorus, serum{15}    (some clinicians recommend monitoring every 6 to 12 months {13} {17})


Hemoglobin and{01}{02}{03}{05}
Platelet count{01}{02}{03}{05}    (recommended monthly {06} to assess effectiveness of imiglucerase therapy; if hemoglobin falls below 7 grams/dL [70 grams/L] and platelet count is under 50,000, monitoring at 2-week intervals may be recommended; {07} both values should increase with treatment)


Liver volume and{01}{02}{03}{05}
Spleen volume{01}{02}{03}{05}    (recommended every 6 months {06} {07} to assess effectiveness of therapy; liver and spleen should decrease in volume with imiglucerase treatment {01} {03} {04})


Magnetic resonance imaging (MRI) of long bones    (some clinicians recommend monitoring every 1 to 2 years; skeletal response should improve with imiglucerase therapy {10} {17})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent {01}
    
Abdominal discomfort
    
decrease in blood pressure
    
decrease in urinary frequency
    
dizziness {02}
    
headache {02}
    
nausea
    
pruritus (itching){02}
    
rash {02}

Note: Decrease in blood pressure, nausea, pruritus, and rash may be due to antibody formation, which occurs in approximately 10 to 16% {01} of patients receiving imiglucerase. Antibody levels decrease in most patients with continuous therapy.






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Imiglucerase (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to alglucerase or imiglucerase

Proper use of this medication
Helps control and reverse problems caused by Gaucher's disease; possible need for lifelong therapy; serious consequences of untreated Gaucher's disease

» Proper dosing

Precautions while using this medication
Importance of monitoring by the physician


Parenteral Dosage Forms

IMIGLUCERASE FOR INJECTION

Usual adult and adolescent dose
Enzyme replenisher
Intravenous infusion, 15 to 60 Units per kg of body weight administered over one to two hours. {13} The usual frequency of infusion is once every two weeks, {01} but disease severity and patient convenience may dictate administration several times a week to once every two weeks. {13} Dosage can be lowered depending on patient response. Dosage may be lowered at 6-month intervals, while monitoring response parameters. {01} {12} {16}


Usual pediatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


200 Units per vial (Rx) [Cerezyme{01}]

Canada—


200 Units per vial (Rx) [Cerezyme{18}]

Packaging and storage:
Store at 2 to 8 °C (36 to 46 °F). {01}

Preparation of dosage form:
On the day of use, the vial is reconstituted with 5.1 mL of Sterile Water for Injection USP to give a volume of 5.3 mL. Then, 5 mL is withdrawn from the vial and diluted with 0.9% Sodium Chloride Injection USP to a final volume of 100 to 200 mL. {01}

Stability:
Imiglucerase does not contain a preservative. The product information for imiglucerase states that when diluted to 50 mL and stored at 2 to 8 °C (36 to 46 °F), the reconstituted product is stable for up to 24 hours. {01}



Revised: 08/13/1998



References
  1. Cerezyme product information (Genzyme—US), Rec 8/94, Rev 5/94.
  1. Grabowski G, Barton N, Pastores G, et al. Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med 1995; 122: 33-9.
  1. Barton N, Brady R, Dambrosia J, et al. Replacement therapy for inherited enzyme deficiency-macrophage-targeted glycocerebrosidase for Gaucher's disease. N Engl J Med 1991; 324: 1464-70.
  1. Beutler E, Kay A, Saven A, et al. Enzyme-replacement therapy for Gaucher's disease [letter to editor]. N Engl J Med 1991; 325 (25); 1809-11.
  1. Barton N, Furbish F, Murray G, et al. Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher's disease. Proc Natl Acad Sci USA 1990; 87: 1913-6.
  1. Reviewer comment on alglucerase monograph, 1992.
  1. Reviewer comment on alglucerase monograph, 1992.
  1. Reviewer comments on alglucerase monograph, 1992.
  1. Reviewer comment, 1995.
  1. Reviewer comment, 1995.
  1. Reviewer comments, 1995.
  1. Reviewer comment, 1995.
  1. Reviewer comment, 1995.
  1. Moscicki T. Adverse reactions and development of antibodies during enzyme replacement therapy. NIH technology assessment conference on Gaucher disease: current issues in diagnosis and treatment. February 27-March 1, 1995: 123–9.
  1. Reviewer comment, 1995.
  1. Reviewer comment, 1995.
  1. Reviewer consensus, 1995.
  1. Personal communication from Genzyme, 1998.
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