Class: Enzymes
ATC Class: A16AB01
VA Class: BL900
Brands: Ceredase
Introduction
Semisynthetic form of human β-glucocerebrosidase (glucosylceramidase).1 3 9 a
Uses for Alglucerase
Gaucher’s Disease
Long-term enzyme replacement therapy in patients with confirmed diagnosis of nonneuronopathic (type 1) Gaucher’s disease that results in one or more of the following conditions: moderate to severe anemia, thrombocytopenia with bleeding tendency, bone disease, and/or clinically important hepatomegaly or splenomegaly1 2 3 11 12 13 14 15 16 28 29 (designated an orphan drug by FDA for this use).22
Replacement therapy in patients with neuronopathic (type 2 or 3)† Gaucher’s disease (designated an orphan drug by FDA for this use).22
Alglucerase Dosage and Administration
General
Administration
IV Administration
Administer by IV infusion.1 3 16 21
May be administered using an infusion apparatus that includes an inline particulate filter.1 27
Dilution
Use strict aseptic technique since drug product contains no preservative.a
Just prior to administration, withdraw appropriate dose of undiluted alglucerase from vial and dilute in 0.9% sodium chloride injection to a final volume of ≤200 mL.a 27 Do not shake.1
Rate of Administration
Administer over 1–2 hours.a 3 11
Dosage
Pediatric Patients
Gaucher's Disease
IV
Children and adolescents 2–16 years of age: Initially, dosage ranges from 2.5 units/kg 3 times weekly to 60 units/kg every 1–4 weeks.a
After patient response is established, attempt to reduce dosage for maintenance therapy.a Further reductions can be made every 3–6 months thereafter.a
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.a
Clinical improvement in hematologic and visceral manifestations generally occurs within 6 months of initiation of therapy;1 11 12 13 16 a response to skeletal manifestations may require several years of therapy.19
Adults
Gaucher's Disease
IV
Adults >16 years of age: Initially, dosage ranges from 2.5 units/kg 3 times weekly to 60 units/kg every 1–4 weeks.a
After patient response is established, attempt to reduce dosage for maintenance therapy.a Further reductions can be made every 3–6 months thereafter, with careful monitoring of response.a
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.a
Clinical improvement in hematologic and visceral manifestations generally occurs within 6 months of initiation of therapy;1 11 12 13 16 a response to skeletal manifestations may require several years of therapy.19
Special Populations
No special population dosage recommendations at this time.
Cautions for Alglucerase
Contraindications
Warnings/Precautions
Sensitivity Reactions
Hypersensitivity Reactions
Hypersensitivity reactions (e.g., pruritus, flushing, urticaria, angioedema, chest discomfort, respiratory symptoms, nausea, abdominal cramping, hypotension) reported during or shortly after IV infusion.a
If hypersensitivity reaction occurs, institute appropriate therapy as indicated; assess serum tryptase level and complement activation within 2 hours of the event after appropriate treatment of the symptoms.a
Use with caution in patients who have exhibited manifestations of hypersensitivity reactions.a Further therapy generally can be administered successfully following a decrease in infusion rate and pretreatment with antihistamines.a
Antibody Formation
Development of IgG antibodies to alglucerase reported in approximately 13% of patients, usually within the first 6 months of therapy and rarely after 12 months of therapy.a
Possible increased risk of hypersensitivity reactions in patients with detectable IgG antibodies.a (See Hypersensitivity Reactions under Cautions.) Monitor periodically for alglucerase IgG antibodies.1 2 a
Decreased efficacy reported in <0.5% of patients due to alglucerase IgG antibodies.a
General Precautions
Risk of Transmissible Agents in Human Placental-derived Preparations
Potential vehicle for transmission of human viruses or other infectious agents.1 12 a
May carry a risk of transmitting slowly acting or latent viruses, including the causative agent of Creutzfeldt-Jakob disease (CJD), although such transmission has not been tested to date, and the risk is considered remote.a
Assess potential benefits and risks of treatment with alglucerase prior to use.1 12
hCG Effects
Risk of hCG related adverse effects (e.g., menstrual abnormalities, false positive pregnancy tests, early virilization in males) due to hCG in the product; however, risk is minimal due to recent manufacturing changes that have reduced the level of hCG in alglucerase.a
Use with caution in patients with androgen sensitive malignancies (e.g., prostate cancer) and in patients with known prior allergies to hCG.a
Specific Populations
Pregnancy
Category C. a
Lactation
Not known whether alglucerase is distributed into milk; caution if used in nursing women.1
Pediatric Use
Safety and efficacy not established in patients <2 years of age, although the drug has been used in this age group. a
Potential early virilization in males <10 years of age.a (See hCG Effects under Cautions.)
Common Adverse Effects
Injection site reactions, slight fever, chills, abdominal discomfort, nausea, vomiting.1 3 27
Alglucerase Pharmacokinetics
Absorption
Onset
Steady-state enzymatic activity achieved within 1 hour during a 4-hour IV infusion.1
Distribution
Extent
Hepatic uptake demonstrated in biopsy specimens.20 21
Elimination
Half-life
Following termination of the IV infusion, plasma enzymatic activity declines linearly with a half-life of 3.6–11 minutes.1 16
Stability
Storage
Parenteral
Powder for Injection
2–8°C.1 27 Do not shake.a Discard partially used vials of undiluted drug.a
Following dilution, stable at 2–8°C for up to 18 hours.a
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Solution Compatibility
Compatible
|
|---|
Sodium chloride 0.9%2
|
ActionsActions
Replaces the deficient endogenous enzyme (glucocerebrosidase; glycosylceramidase) in patients with Gaucher’s disease.1 2 3 5 12 a
Catalyzes the hydrolysis of the β-glycoside linkage of glucosylceramide (glucocerebroside) within macrophages1 2 4 7 to glucose and ceramide (N-acylsphingosine) 1 4 8 with resultant improvement in hemoglobin concentration, hematocrit, and erythrocyte and platelet counts, and a reduction in splenomegaly and hepatomegaly.1 2 3 11 12 13 14 15
Advice to Patients
Risk of hypersensitivity reactions (pruritus, flushing, urticaria, angioedema, chest discomfort, respiratory symptoms, nausea, abdominal cramping, hypotension).a
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a
Importance of informing patients of other important precautionary information.a (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Alglucerase (Human Tissue Origin)
Routes
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Dosage Forms
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Strengths
|
Brand Names
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Manufacturer
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|---|
Parenteral
|
For injection concentrate, for IV infusion
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80 units/mL
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Ceredase
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Genzyme
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Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. Genzyme Corporation. Ceredase (alglucerase) prescribing information. Cambridge, MA; 1992 Feb.
2. Barton NW, Furbish FS, Murray GJ et al. Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. Proc Natl Acad Sci USA. 1990; 87:1913-6. [PubMed 2308952]
3. Anon. Alglucerase for Gaucher’s disease. Med Lett Drugs Ther. 1991; 33:82. [PubMed 1865852]
4. Brady RO, Kanfer JN, Shapiro D. Metabolism of glucocerebrosides: II. Evidence of an enzymatic deficiency in Gaucher’s disease. Biochem Biophys Res Commun. 1965; 18:221-5. [PubMed 14282020]
5. Britton DE, Leinikki PO, Barranger JA et al. Gaucher’s disease: lack of antibody response to intravenous glucocerebrosidase. Life Sci. 1978; 23:2517-20. [PubMed 732537]
6. Stahl PD, Rodman JS, Miller MJ et al. Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. Proc Natl Acad Sci USA. 1978; 75:1399-1403. [PubMed 274729]
7. Basu A, Prence E, Garrett K et al. Comparison of N-acyl phosphatidylethanolamines with different N-acyl groups as activators of glucocerebrosidase in various forms of Gaucher’s disease. Arch Biochem Biophys. 1985; 243:28-34. [PubMed 3933429]
8. Furbish FS, Blair HE, Shiloach J et al. Enzyme replacement therapy in Gaucher’s disease: large-scale purification of glucocerebrosidase suitable for human administration. Proc Natl Acad Sci USA. 1977; 74:3560-3. [PubMed 269414]
9. Genzyme Corporation, Boston, MA: Personal communication.
10. Webb EC, preparer. Enzyme nomenclature 1984: recommendations of the Nomenclature Committee of the International Union of Biochemistry on the nomenclature and classification of enzyme-catalyzed reactions. Orlando, FL: Academic Press, Inc; 1984.
11. Barton NW, Brady RO, Dambrosia JM et al. Replacement therapy for inherited enzyme deficiency—macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med. 1991; 324:1464-70. [IDIS 280934] [PubMed 2023606]
12. Beutler E. Gaucher’s disease. N Engl J Med. 1991; 325:1354-60. [IDIS 287428] [PubMed 1922238]
13. Beutler E, Kay AC, Saven A et al. Enzyme-replacement therapy for Gaucher’s disease. N Engl J Med. 1991; 325:1809-10. [IDIS 289025] [PubMed 1944489]
14. Zimran A, Hadas-Halpern I, Abrahamov A et al. Enzyme-replacement therapy for Gaucher’s disease. N Engl J Med. 1991; 325:1810-1.
15. Barton NW, Brady RO, Murray GJ et al. Enzyme-replacement therapy for Gaucher’s disease. N Engl J Med. 1991; 325:1811. [IDIS 289028] [PubMed 1944490]
16. Beutler E, Kay A, Saven A et al. Enzyme replacement therapy for Gaucher disease. Blood. 1991; 78:1183-9. [IDIS 288172] [PubMed 1878585]
17. Parker RI, Barton NW, Read EJ et al. Hematologic improvement in a patient with Gaucher disease on long-term enzyme replacement therapy: evidence for decreased splenic sequestration and improved red blood cell survival. Am J Hematol. 1991; 38:130-7. [PubMed 1951303]
18. Murray GJ, Howard KD, Richards SM et al. Gaucher’s disease: lack of antibody response in 12 patients following repeated intravenous infusions of mannose terminal glucocerebrosidase. J Immunol Methods. 1991; 137:113-20. [PubMed 2010615]
19. Barton NW, Brady RO, Dambrosia JM et al. Dose-dependent responses to macrophage-targeted glucocerebrosidase in a child with Gaucher disease. J Pediatr. 1992; 120:277-80. [IDIS 292694] [PubMed 1735829]
20. Genzyme Corporation. Ceredase treatment protocol: investigators’ brochure. IND No. 31,345. Boston, MA: 1990 Feb 6.
21. Reviewers’ comments (personal observations).
22. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food Drug and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 28, 1996. Rockville, MD; 1996 Jul.
23. Barton NW, Murray GJ, Brady NO. Hematological responses are dependent on the amount of glucocerebrosidase administered to patients with Gaucher’s disease. Blood. 1991; 78(Suppl 1):431a.
24. Beutler E, Dale GL, Kuhl W. Enzyme replacement therapy in Gaucher’s disease: preliminary clinical trial of a new enzyme preparation (glucocerebrosidase). Proc Natl Acad Sci. 1977; 74:4620-3. [PubMed 200923]
25. Beutler E. Gaucher disease. Blood. 1988; 2:59-70.
26. Tsuji J, Choudary PV, Martin BM et al. Nucleotide sequence of cDNA containing the complete coding sequence for lysosomal glucocerebrosidase. J Biol Chem. 1986; 261:50-3. [PubMed 3001061]
27. Genzyme, Boston, MA: Personal communication.
28. Figueroa ML, Rosenbloom BE, Kay AC et al. A less costly regimen of alglucerase to treat Gaucher’s disease. N Engl J Med. 1992; 327:1632-6. [IDIS 305875] [PubMed 1435900]
29. Garber AM. No price too high? N Engl J Med. 1992; 327:1676-8. Editorial.
a. Genzyme Corporation. Ceredase (alglucerase) injection solution concentrate prescribing information. Cambridge, MA; 1996 Nov. Available at: (). Accessed 2007 Sep 28.
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