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 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

Indications and Usage

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

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 57,000.4

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, or by GAA gene sequencing

In the table below, options to determine DNA mutations or GAA activity, are listed from the least invasive to most invasive (top to bottom)

lumizyme_options_to_determine_gaa_activity_revised

Resources

Full Prescribing Information (PDF)

Lumizyme Fact Sheet (PDF)

Indication

LUMIZYME® (alglucosidase alfa) is an enzyme replacement therapy for patients with Pompe disease (acid α-glucosidase (GAA) deficiency).

Important Safety Information

WARNING: Risk of anaphylaxis, hypersensitivity and immune-mediated reactions, and risk of cardiorespiratory failure

  • If you or your child is taking Lumizyme, you should know that severe and potentially life-threatening allergic-type reactions known as anaphylaxis or severe hypersensitivity reactions, and other severe reactions related to the immune system may occur during and after Lumizyme treatment. Reactions may include, for example, kidney dysfunction, extreme difficulty breathing, shallow breathing, abnormal heart rate, low blood pressure, or throat tightness (including face, tongue and lip swelling) and skin lesions.
  • If you or your child experiences these severe reactions, you may require close observation during and after Lumizyme administration. You should discuss with your physician the signs and symptoms of anaphylaxis and hypersensitivity reactions and seek immediate medical care should they occur. Anaphylaxis or severe hypersensitivity reactions are potentially very dangerous. If such a reaction is severe enough, your doctor may decide to immediately discontinue the infusion and provide immediate medical care. Appropriate medical support measures may be administered when you are being infused with Lumizyme.
  • If your child has a current respiratory condition or illness and has compromised breathing or heart function due to Pompe disease, there may be risk of acute worsening of heart and/or lung function with Lumizyme due to the fluid of the infusion, and your doctor may decide that close observation during and after Lumizyme administration may be necessary.

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 such a reaction is severe enough, your doctor may decide to immediately discontinue the infusion and provide you with immediate medical care. Appropriate medical support and monitoring measures should be available during infusion.

Immune-Mediated Reactions: You or your child may be monitored for the development of systemic immune-mediated reactions while receiving Lumizyme. If these reactions occur, your doctor may discontinue the infusion and initiate appropriate medical treatment.

Risk of Acute Cardiorespiratory Failure: Infant Pompe patients with heart or breathing problems who are experiencing an acute respiratory condition may be at risk for increasing the seriousness of these problems as a result of Lumizyme administration due to the infusion fluid, and your child’s doctor may require additional monitoring for these infants.

Risk of Cardiac Arrhythmia and Sudden Cardiac Death during General Anesthesia for Central Venous Catheter Placement: Caution should be used when administering general anesthesia for the placement of a central venous catheter intended for Lumizyme infusion. Ventricular arrhythmias and slow heart rate resulting in cardiac arrest or death have been observed in infant Pompe patients with cardiac hypertrophy during general anesthesia for central venous catheter placement. Appropriate medical support and monitoring measures should be available during infusion.

Risk of Antibody Development: Since Lumizyme is a protein, it is possible that patients receiving it develop antibodies. Some patients who develop high IgG antibody levels that last for a while may have reduced response to Lumizyme. 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 during Lumizyme studies in patients were allergy reactions and included: anaphylaxis, rash, fever, flushing/feeling hot, hives, headache, excessive sweating, nausea, cough, less oxygen in the blood, fast heart rate, rapid breathing, chest discomfort, dizziness, muscle twitching, agitation, bluish or purple skin, redness of skin, high blood pressure/increased blood pressure, facial paleness, chills, tremor, vomiting, fatigue, and muscle pain.

Special populations

If you are pregnant, you should use Lumizyme only if your doctor has determined that its use outweighs any risks to your unborn child.

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.