Dosing & Uses
Dosing Form & Strengths
injectable solution
- 80 units/mL (400 units/vial)
Gaucher Disease
Indicated for long-term enzyme replacement therapy for type I Gaucher disease in patients with signs and symptoms severe enough to result in anemia, thrombocytopenia, bone disease, or hepatomegaly/splenomegaly
Individualize dose: Initial dose may be as little at 2.5 units/kg IV 3 times/week up to as much as 60 units/kg IV as frequent as qWeek, or as infrequently as q4weeks
60 Units/kg IV q2weeks is the dose for which the most data are available
Disease severity may dictate that drug be initiated with relatively high doses or relatively frequent administration; after patient response is well-established, a reduction in dosage may be attempted for maintenance therapy; progressive reductions can be made at intervals of 3-6 months while carefully monitoring response parameters
Administration
Pretreat with antihistamine before administration to reduce risk of infusion related reactions
Infuse IV over 1-2 hr
Dosing Considerations
Derived from human placenta tissue donors
Has been largely replaced by the recombinant product, imiglucerase (Cerezyme)
Prepared on a batch-by-batch basis for a few patients unable to tolerate or do not respond well to the newer product
Dosing Form & Strengths
injectable solution
- 80 units/mL (400 units/vial)
Gaucher Disease
Indicated for long-term enzyme replacement therapy for type I Gaucher disease in patients with signs and symptoms severe enough to result in anemia, thrombocytopenia, bone disease, or hepatomegaly/splenomegaly
Individualize dose: Initial dose may be as little at 2.5 units/kg IV 3 times/week up to as much as 60 units/kg IV as frequent as qWeek, or as infrequently as q4weeks
60 Units/kg IV q2weeks is the dose for which the most data are available
Disease severity may dictate that drug be initiated with relatively high doses or relatively frequent administration; after patient response is well-established, a reduction in dosage may be attempted for maintenance therapy; progressive reductions can be made at intervals of 3-6 months while carefully monitoring response parameters
Administration
Pretreat with antihistamine before administration to reduce risk of infusion related reactions
Infuse IV over 1-2 hr
Other Information
Derived from human placenta tissue donors
Has been largely replaced by the recombinant product, imiglucerase (Cerezyme)
Prepared on a batch-by-batch basis for a few patients unable to tolerate or do not respond well to the newer product
Adverse Effects
Frequency Not Defined
Discomfort, pruritus, burning, swelling, sterile abscess at venipuncture site
Mild fever
Chills
Abdominal discomfort
Nausea
Vomiting
Hypersensitivity symptoms during or shortly following infusion (eg, pruritus, flushing, urticaria, respiratory symptoms, nausea, abdominal cramping, hypotension)
Postmarketing Reports
Severe and serious infusion reactions including anaphylactic shock
Acute cardiorespiratory failure, possibly associated with fluid overload (in patients with pre-existing hypertrophic cardiomyopathy
Cardiac/respiratory arrest
Apnea
Stridor
Pharyngeal edema
Peripheral edema
Chest pain/discomfort
Muscle spasm
Fatigue
Conjunctivitis
Proteinuria and nephrotic syndrome
Systemic and cutaneous immune mediated reactions, including ulcerative and necrotizing skin lesions, and nephrotic syndrome secondary to membranous glomerulonephritis
Warnings
Contraindications
None known
Cautions
IgG antibodies develop in about 13% during first year of treatment
Approximately 25% of patients with detectable IgG antibodies experience hypersensitivity
Derived from pooled human placental tissue that may contain viral agents; manufacturing steps are designed to reduce viral transmission risk
Monitor for signs of early virilization in males younger than 10 years since hCG has been detected in alglucerase
Pregnancy & Lactation
Pregnancy Category: C
Lactation: May be excreted in breast milk, caution advised
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Catalyzes the hydrolysis of the glycolipid, glucocerebroside, to glucose and ceramide as part of the normal degradation pathway for membrane lipids; enzyme replacement for conditions with functional deficiency in beta-glucocerebrosidase enzymatic activity to prevent accumulation of lipid glucocerebroside
Pharmacokinetics
Half-Life: 3.6-10.4 minutes
Vd: 49.4-282.1 mL/kg
Clearance: Variable; 6.23-25.39 mL/min/kg
Administration
IV Compatibilities
Solution: 0.9% NaCl
IV Preparation
Do NOT shake vial
Inspect bottle for particulate matter and discoloration before use; do not use if particulate matter or discoloration exhibited
IV infusion: Dilute injectable solution further with 0.9% NaCl; not to exceed volume of 200 mL
IV Administration
Use an inline particulate filter during infusion
Infuse IV over 1-2 hours
Storage
May store diluted solution for up to 18 hr at 2-8 degrees C
Does not contain any preservative; after opening, bottles should not be stored for subsequent use
