Patients & Families
IMPORTANT SAFETY INFORMATION: WARNING: RISK OF ANAPHYLAXIS, HYPERSENSITIVITY AND IMMUNE-MEDIATED REACTIONS, AND RISK OF CARDIORESPIRATORY FAILURE Life-threatening anaphylactic reactions and severe hypersensitivity reactions, presenting as respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria, have occurred in some patients during and after alglucosidase alfa infusions. Immune-mediated reactions presenting as proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following alglucosidase alfa treatment. View more

PRESCRIBING LUMIZYME

 

About Pompe Disease

Pompe disease—also known as acid maltase deficiency or glycogen-storage disease type 2—is a progressive, debilitating, and often fatal neuromuscular disorder. It was first identified in 1932 by Johannes C. Pompe3 and has an incidence in older children and adults of about 1 in 40,000.4

Caused by a deficiency of the enzyme acid alfa glucosidase (GAA), Pompe disease is characterized by progressive glycogen accumulation primarily in the lysosomes of muscle cells. It is an autosomal recessive genetic disorder, affecting both sexes equally.

Early Diagnosis Is Key

  • Pompe disease is progressive, even in the absence of overt signs and symptoms
  • Early diagnosis is important to disease management
  • Pompe disease symptoms are seen in other neuromuscular disorders, so a definitive diagnosis is important to determine appropriate treatment options
  • Fortunately, a diagnosis can be easily confirmed by enzyme assay demonstrating low GAA activity and by GAA gene sequencing

Related Information

 

Indication

LUMIZYME® (alglucosidase alfa) is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (GAA deficiency).

Important Safety Information

WARNING: RISK OF ANAPHYLAXIS, HYPERSENSITIVITY AND IMMUNE-MEDIATED REACTIONS, AND RISK OF CARDIORESPIRATORY FAILURE

  • Life-threatening anaphylactic reactions and severe hypersensitivity reactions, presenting as respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria, have occurred in some patients during and after alglucosidase alfa infusions. Immune-mediated reactions presenting as proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following alglucosidase alfa treatment. Closely observe patients during and after alglucosidase alfa administration and be prepared to manage anaphylaxis and hypersensitivity reactions. Inform patients of the signs and symptoms of anaphylaxis, hypersensitivity reactions, and immune-mediated reactions and have them seek immediate medical care should signs and symptoms occur.
  • Infantile-onset Pompe disease patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to fluid overload, and require additional monitoring.

Warnings and Precautions

Anaphylaxis and Hypersensitivity Reactions: Life-threatening anaphylaxis and hypersensitivity reactions have been observed in some patients during and after treatment with alglucosidase alfa. If anaphylaxis or severe hypersensitivity reactions occur, immediately discontinue infusion and institute appropriate medical treatment. Appropriate medical support and monitoring measures should be available during infusion.

Immune-Mediated Reactions: Monitor patients for the development of systemic immune-mediated reactions involving skin and other organs. If immune-mediated reactions occur, consider discontinuation of the administration of alglucosidase alfa, and initiate appropriate medical treatment.

Risk of Acute Cardiorespiratory Failure: Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during alglucosidase alfa infusion, and some patients may require prolonged observation times that should be individualized based on the needs of the patient.

Risk of Cardiac Arrhythmia and Sudden Cardiac Death during General Anesthesia for Central Venous Catheter Placement: Administration of general anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness. Therefore, caution should be used when administering general anesthesia. Ventricular arrhythmias and bradycardia, resulting in cardiac arrest or death, or requiring cardiac resuscitation or defibrillation have been observed in infantile-onset Pompe disease patients with cardiac hypertrophy during general anesthesia for central venous catheter placement.

Risk of Antibody Development: Patients with infantile-onset Pompe disease should have a cross-reactive immunologic material (CRIM) assessment early in their disease course and be managed by a clinical specialist knowledgeable in immune tolerance induction in Pompe disease to optimize treatment. CRIM status has been shown to be associated with immunogenicity and patients’ responses to enzyme replacement therapies. There is evidence to suggest that some patients who develop high and sustained IgG antibody titers, including CRIM-negative patients, may experience reduced clinical alglucosidase alfa treatment efficacy.

Monitoring: Laboratory Tests: Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter.

Adverse Reactions

The most frequently reported adverse reactions (≥ 5%) in clinical trials were hypersensitivity reactions and included: anaphylaxis, rash, pyrexia, flushing/feeling hot, urticaria, headache, hyperhidrosis, nausea, cough, decreased oxygen saturation, tachycardia, tachypnea, chest discomfort, dizziness, muscle twitching, agitation, cyanosis, erythema, hypertension/increased blood pressure, pallor, rigors, tremor, vomiting, fatigue, and myalgia.

Please see the Full Prescribing Information for complete details, including boxed WARNING.

  

References

  1. Lumizyme Full Prescribing Information, Genzyme Corporation
  2. Van der Ploeg et al, A randomized study of alglucosidase alfa in late-onset Pompe’s disease. N Engl J Med 2010, 362;15; 1396-1406.
  3. Kishnani PS, Howell RR. Pompe disease in infants and children. J Pediatr 2004; 144:S35-S43.
  4. Ausems MG, Verbiest J. Hermans MP, et al. Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis and genetic counselling. Eur J Hum Genet 1999; 7:713-6.
  5. American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM). Diagnostic criteria for late-onset (childhood and adult) Pompe disease. Muscle Nerve. 2009;40(1):149-160.
  6. Goldstein JL, Young SP, Changela M, et al. Screening for Pompe disease using a rapid dried blood spot method: experience of a clinical diagnostic laboratory. Muscle Nerve. 2009:40(1):32-36.
  7. Zhang H, Kallwass H, Young SP, et al. Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet med 2006; 8:302-306.
  8. Jack RM, Gordon C, Scott CR, Kishnani PS, Bali D. The use of acarbose inhibition in the measurement of acid alpha-glucosidase a ctivity in blood lymphocytes for the diagnosis of Pompe disease. Genet Med 2006;8:307-312.
  9. Hirschhorn R, Reuser AJJ. Glycogen storage disease type II: acid alpha-gluscosidase (acid maltase) deficiency. In: Scriver CR, Beaudet AL, Sly WS, et al, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001:3389-3420
  10. Okumiya T, Keulemans J, Kroos M, Van der Beek N, Boer M, Takeuchi H, et al. A new diagnostic assay for glycogen storage disease type II in mixed leukocytes. Mol Genet Metab 2006;88:22-8
  11. van Diggelen O, Oemardien L, van der Beek N, Kroos M, Wind H, Voznyi Y, et al. Enzyme analysis for Pompe disease in leukocytes; superior results with natural substrate compared with artificial substrates. J Inherit Metab Dis 2009;32:416-23.
  12. Li Y, Scott C, Chamoles N, Ghavami A, Pinto B, Turecek F, et al. Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening. Clin Chem 2004;50:1785-96.
  13. Winchester B, Bali D, Bodamer OA, et al; for Pompe Disease Diagnostic Working Group. Methods for a prompt and reliable laboratory diagnosis of Pompe disease: report from an international consensus meeting. Mol Genet Metab. 2008;93(3):275-281.
  14. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med. 2006;8(5):267-288.
  15. Kishnani PS, Howell RR. Pompe disease in infants and children. J Pediatr 2004; 144:S35-S43.
  16. Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med 2006; 8:267-88.
  17. Okumiya, et al. A new diagnostic assay for GSD type II in mixed leukocytes. Mol Genet Met. 2006; 88:22-28.
  18. Van Diggelsen, et al. Enzyme anlaysis for Pompe disease in leukocytes; superior results with natural substrate compared with artificial substrates. J Inherit Metab Dis. 2009; 32: 416-423.
  19. Li, et al. Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening. Clin Chem 2004; 50: 1785-1796.
  20. Case LE, Kishnani PS. Physical therapy management of Pompe disease. Genet Med. 2006;8(5):318-327.
  21. Aitkens SG, McCrory MA, Kimer DD, Bernauer EM. Moderate resistance exercise program: its effect in slowly progressive neuromuscular disease. Arch Phys Med Rehabil. 1993;74(7):711-715.
  22. Hagemans ML, Laforet P, Hop WJ et al (2007a) Impact of late-onset Pompe disease on participation in daily life activities: evaluation of the Rotterdam Handicap Scale. Neuromuscul Disord 17:537-543.

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