Generic Name: Velaglucerase Alfa
Chemical Name: Ceramidase, glucosyl-(human HT-1080 cell)
Molecular Formula: C2532H3854N672O711S16
CAS Number: 0884604-91-5
Biosynthetic (gene activation technology origin) form of human β-glucocerebrosidase (glucosylceramidase).1 3 4 33
Uses for VPRIV
Long-term enzyme replacement therapy in patients with nonneuronopathic (type 1) Gaucher's disease1 5 32 33 (designated an orphan drug by FDA for this use).2
VPRIV Dosage and Administration
Administer under the supervision of a clinician.1
For solution compatibility information, see Compatibility under Stability.
Administer by IV infusion.1
Administer using an inline, low-protein-binding, 0.2-mcm particulate filter.1
Velaglucerase alfa does not contain preservatives; prepare solutions immediately before use.1 If immediate use is not possible, complete infusion within 24 hours of reconstitution.1
Determine number of vials to be reconstituted based on patient weight.1
Reconstitute appropriate number of vials containing 200 or 400 units of velaglucerase alfa lyophilized powder with 2.2 or 4.3 mL of sterile water for injection, respectively, to provide a solution containing 100 units/mL.1 Mix gently; do not shake vial.1
Withdraw appropriate dose from reconstituted vials and dilute with 100 mL of 0.9% sodium chloride injection.1 Mix solution gently; do not shake.1
Rate of Administration
Administer over 1 hour.1
Children and adolescents 4–17 years of age: Initially, 60 units/kg every 2 weeks.1
Adjust dosage based on achievement and maintenance of patient's therapeutic goals; dosages ranging from 15–60 units/kg every 2 weeks were evaluated in clinical trials.1
Patients receiving imiglucerase can be switched to velaglucerase alfa at an equivalent dosage.1
Initially, 60 units/kg every 2 weeks.1
Adjust dosage based on achievement and maintenance of the patient's therapeutic goals; dosages ranging from 15–60 units/kg every 2 weeks were evaluated in clinical trials.1
Patients receiving imiglucerase can be switched to velaglucerase alfa at an equivalent dosage.1
Cautions for VPRIV
No known contraindications.1
Hypersensitivity reactions reported.1
Carefully reevaluate therapy if substantial clinical evidence of hypersensitivity develops.1 Treat severe hypersensitivity reactions in accordance with current emergency practice standards; appropriate medical support should be readily available.1
Use with caution in patients who have exhibited manifestations of hypersensitivity reactions to velaglucerase alfa, any ingredient in the formulation, or other enzyme replacement therapy.1
Infusion-related reactions (e.g., headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, pyrexia) reported.1
Depending on severity, manage infusion-related reactions by slowing the infusion rate, providing appropriate medical treatment (e.g., antihistamines, antipyretics, and/or corticosteroids), and/or interrupting and then resuming treatment at a slower infusion rate.1
Pretreatment with antihistamines and/or corticosteroids may prevent subsequent reactions in patients who have experienced infusion-related reactions requiring treatment.1
Development of IgG antibodies to velaglucerase alfa reported.1 Effect on risk of infusion reactions is not known.1
Continue to monitor for antibodies in patients with an immune response to other enzyme replacement therapies who are switched to velaglucerase alfa.1
Not known whether velaglucerase alfa is distributed into milk.1 Use with caution.1
Safety and efficacy not established in children <4 years of age.1
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.1
Common Adverse Effects
Infusion-related reactions, headache, upper respiratory tract infection, dizziness, pyrexia, abdominal pain, back pain, joint (knee) pain, asthenia/fatigue, prolonged aPTT, nausea.1
Upper respiratory tract infection, rash, prolonged aPTT, and pyrexia reported more frequently in pediatric patients than in adults.1
Interactions for VPRIV
Formal drug interaction studies not performed to date.1
Accumulation not observed in patients receiving 60 units/kg every 2 weeks for 37 weeks.1
Not known whether velaglucerase alfa distributes into milk.1
Powder for Injection
2–8°C; protect from light.1 Do not freeze.1
Following reconstitution or dilution, 2–8°C for up to 24 hours; protect from light; do not freeze.1
For information on systemic interactions resulting from concomitant use, see Interactions.
Sodium chloride 0.9%
Replaces the deficient endogenous enzyme (β-glucocerebrosidase; glucosylceramidase) in patients with Gaucher’s disease.1 3 4
Enzyme replacement therapy for type 1 Gaucher's disease increases the degradation of glucosylceramide (glucocerebroside) in macrophages1 3 4 5 7 8 10 26 27 by hydrolyzing the β-glycoside linkage of glucocerebroside to glucose and ceramide (N-acylsphingosine) 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.4 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Advice to Patients
Risk of hypersensitivity and infusion-related reactions.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information. (See Cautions.)1
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.
For injection, for IV infusion
AHFS DI Essentials. © Copyright 2017, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
1. Shire Human Genetic Therapies, Inc. VPRIV (velaglucerase alfa for injection) prescribing information. Cambridge, MA; 2010 Feb. Available at . Accessed 2011 Dec 5.
2. Food and Drug Administration. Cumulative list of orphan drugs designated and/or approved. Rockville, MD; 2009 Jun 8. Available at . Accessed 2011 Dec 14.
3. Burrow TA, Grabowski GA. Velaglucerase alfa in the treatment of Gaucher disease type 1. Clin Invest. 2011; 1:285-93.
4. Cox TM. Gaucher disease: clinical profile and therapeutic developments. Biologics. 2010; 4:299-313. [PubMed 21209725]
5. Zimran A, Altarescu G, Philips M et al. Phase 1/2 and extension study of velaglucerase alfa and replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood. 2010; 115:4651-6. [PubMed 20299511]
6. Beutler E. Gaucher's disease. N Engl J Med. 1991; 325:1354-60. [PubMed 1922238]
7. Genzyme Corporation. Cerezyme (imiglucerase) for injection prescribing information. Cambridge, MA; 2003 Mar.
8. 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]
9. Anon. Alglucerase for Gaucher’s disease. Med Lett Drugs Ther. 1991; 33:82. [PubMed 1865852]
10. Genzyme Corporation. Ceredase (alglucerase) prescribing information. Cambridge, MA; 1992 Feb.
11. Reviewers’ comments (personal observations) on alglucerase.
12. Weinreb NJ, Charrow J, Andersson HC et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Register. Am J Med. 2002; 113:112-9. [PubMed 12133749]
13. Niederau C, Haussinger D. Gaucher’s disease: a review for the internist and hepatologist. Hepatogastroenterology. 2000; 47:984-7. [PubMed 11020862]
14. Charrow J, Andersson HC, Kaplan P et al. Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: Consensus recommendations. J Pediatrics. 2003; 144:112-20.
15. Rosenthal DI, Doppelt SH, Mankin HL et al. Enzyme therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics. 1995; 96:629-37. [PubMed 7567322]
16. Grabowski GA, Barton NW, Pastores G et al. Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase form natural and recombinant sources. Ann Intern Med. 1995; 122:33-9. [PubMed 7985893]
17. Actelion Pharmaceuticals. Zavesca (miglustat) capsules prescribing information. South San Francisco, CA; 2003 Jul 31.
18. Elstein D, Abrahamov A, Hadas-Halpern I et al. Low-dose low-frequency imiglucerase as a starting regimen of enzyme replacement therapy for patients with type I Gaucher disease. QJM. 1998; 91:483-8. [PubMed 9797931]
19. Poll LW, Maas M, Terk MR et al. Response of Gaucher bone disease to enzyme replacement therapy. Br J Radiol. 2002; 75(Suppl 1):A25-36.
20. Genzyme Corporation, Cambridge, MA: Personal communication.
21. 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]
22. Beutler E, Kay AC, Saven A et al. Enzyme-replacement therapy for Gaucher’s disease. N Engl J Med. 1991; 325:1809-10. [PubMed 1944489]
23. Zimran A, Hadas-Halpern I, Abrahamov A et al. Enzyme-replacement therapy for Gaucher’s disease. N Engl J Med. 1991; 325:1810-1.
24. Barton NW, Brady RO, Murray GJ et al. Enzyme-replacement therapy for Gaucher’s disease. N Engl J Med. 1991; 325:1811. [PubMed 1944490]
25. 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]
26. 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]
27. 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]
28. 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. [PubMed 2023606]
29. Beutler E, Kay A, Saven A et al. Enzyme replacement therapy for Gaucher disease. Blood. 1991; 78:1183-9. [PubMed 1878585]
30. 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]
31. 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. [PubMed 1735829]
32. Anon. Velaglucerase (Vpriv) for Gaucher's disease. Med Lett Drugs Ther. 2010; 52:36.
33. Elstein D, Cohn GM, Wang N et al. Early achievement and maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease. Blood Cells Mol Dis. 2011; 46:119-23. Epub 2010 Aug 19. [PubMed 20727796]
34. Elstein D, Foldes AJ, Zahrieh D et al. Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction. Blood Cells Mol Dis. 2011; 47:56-61. Epub 2011 May 4. [PubMed 21536468]
35. Elstein D, Altarescu G, Maayan H et al. Booster-effect with velaglucerase alfa in patients with Gaucher disease switched from long-term imiglucerase therapy: Early Access Program results from Jerusalem. Blood Cells Mol Dis. 2012; 48:45-50. Epub 2011 Nov 1. [PubMed 22047948]
36. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 22-575: Chemistry review(s). From FDA website.
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