Alglucosidase Alfa

Name: Alglucosidase Alfa

Alglucosidase Alfa Brand Names

Alglucosidase Alfa may be found in some form under the following brand names:

  • Lumizyme

  • Myozyme

Cautions for Alglucosidase Alfa

Contraindications

  • The manufacturer states that there are no known contraindications.1

Warnings/Precautions

Warnings

Respiratory Effects

Acute cardiorespiratory failure requiring intubation and inotropic support has been observed up to 72 hours after alglucosidase alfa infusion in patients with infantile-onset Pompe disease and underlying cardiac hypertrophy; may be associated with fluid overload secondary to IV infusion of alglucosidase alfa.1

Possible increased risk of acute cardiorespiratory failure in patients with underlying acute illness at time of alglucosidase alfa infusion.1 Ensure that appropriate medical support and monitoring measures are readily available during the infusion.1 Infants with cardiac dysfunction may require prolonged observation times, individualized based on the needs of the patient.1

Cardiac Effects

Risk of cardiac arrhythmias (e.g., ventricular fibrillation, ventricular tachycardia, bradycardia); potentially fatal and may require cardiac resuscitation or defibrillation.1 Such arrhythmias have been associated with use of general anesthesia for placement of central venous catheter intended for IV infusion of the drug in patients with infantile-onset Pompe disease and cardiac hypertrophy.1 Use caution when administering general anesthesia in such patients.1

Infusion Reactions

Infusion reactions, sometimes severe, reported; manifestations include rash, flushing, urticaria, fever, cough, tachycardia, decreased oxygen saturation, vomiting, tachypnea, agitation, cyanosis, hypertension, irritability, pallor, pruritus, retching, rigors, tremor, hypotension, bronchospasm, erythema, facial edema, hot sensation, headache, hyperHIDrosis, increased lacrimation, livedo reticularis, nausea, periorbital edema, restlessness, and wheezing.1 In some cases, infusion reactions occurred in patients who received prophylactic treatment with antihistamines, antipyretic agents, and/or corticosteroids.1 Infusion reactions are more likely to occur with higher infusion rates, but may occur at any time during or up to 2 hours after IV infusion of the drug.1

Possible increased risk of severe complications from infusion reactions in patients with advanced Pompe disease and compromised cardiac and respiratory functions.1 Additional monitoring required in such patients during administration of alglucosidase alfa.1

Possible increased risk of infusion reactions in patients with underlying acute illness at time of alglucosidase alfa infusion.1 Carefully consider patient’s clinical status prior to administration of the drug.1

May administer antipyretics and/or antihistamines prior to alglucosidase alfa infusion.1 If an infusion reaction occurs regardless of pretreatment, decreasing rate of infusion, temporarily discontinuing infusion, and/or administering antihistamines and/or antipyretic agents may ameliorate symptoms.1 If a severe reaction occurs, consider immediate discontinuance of alglucosidase alfa infusion and initiate appropriate medical treatment.1 Use caution when readministering alglucosidase alfa in patients who have experienced infusion reactions.1

Sensitivity Reactions

Hypersensitivity Reactions

Severe and potentially life-threatening hypersensitivity reactions (e.g., anaphylactic shock, cardiac arrest, respiratory distress, hypotension, bradycardia, hypoxia, bronchospasm, throat tightness, dyspnea, angioedema, urticaria) reported during and within 3 hours after alglucosidase alfa infusion.1 Anaphylactic shock and/or cardiac arrest reported in approximately 1% of patients receiving alglucosidase alfa in clinical trials and postmarketing experience.1

Ensure that appropriate medical support measures, including CPR equipment, are readily available.1

If anaphylactic or other severe allergic reaction occurs, consider immediate discontinuance of alglucosidase alfa and institute appropriate therapy as indicated.1 Treatment has included cardiopulmonary resuscitation, mechanical ventilatory support, oxygen supplementation, IV fluids, hospitalization, inhaled β-adrenergic agonists, epinephrine, and IV corticosteroids.1

Use extreme caution and ensure appropriate resuscitation measures are available if alglucosidase alfa is readministered in a patient who has experienced anaphylaxis or other severe allergic reaction.1

General Precautions

Immunologic Reactions and Antibody Formation

Severe cutaneous and systemic immune-mediated reactions (e.g., ulcerative and necrotizing skin lesions, possible type III immune complex-mediated reactions, severe inflammatory arthropathy associated with fever and elevated erythrocyte sedimentation rate) reported.1 Reactions occurred several weeks to 3 years following initiation of alglucosidase alfa therapy.1 Monitor patients for the development of systemic immune complex-mediated reactions involving skin and other organs.1

Possible formation of antibodies to alglucosidase alfa.1 2 5 Monitor patients for IgG antibody formation every 3 months; contact Genzyme Corporation at 800-745-4447 for information on testing and to obtain a sample collection box.1 The effect of antibody development on the long-term efficacy of alglucosidase alfa is not fully known; some patients who develop high and sustained anti-alglucosidase alfa antibody titers have experienced a poorer clinical response and/or reduced motor function.1 5 Infusion reactions to alglucosidase alfa appear to be more common in antibody-positive patients.1 (See Infusion Reactions under Cautions.)

Hepatic Effects

Hepatic accumulation of acid α-glucosidase (GAA) observed in preclinical studies of alglucosidase alfa.1 The manufacturer recommends measurement of hepatic enzyme concentrations before initiation of alglucosidase alfa and periodically thereafter.1 Caution recommended in interpretation of these measurements since increased ALT and AST concentrations may be associated with muscle pathology in patients with Pompe disease.1

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether alglucosidase alfa is distributed into milk.1 Caution if used in nursing women.1

Pediatric Use

Patients 1 month to 3.5 years of age at time of first infusion have received alglucosidase alfa in clinical trials.1

Older pediatric patients (2–16 years of age) also have received alglucosidase alfa in open-label clinical trials; however, safety and efficacy of alglucosidase alfa have not been established in patients with juvenile-onset Pompe disease.1

Geriatric Use

No experience in patients ≥65 years of age; unknown whether geriatric patients respond differently than younger subjects.1

Common Adverse Effects

Pyrexia, cough, decreased oxygen saturation, respiratory distress, respiratory failure, rhinorrhea, tachypnea, pneumonia, otitis media, upper respiratory tract infection, gastroenteritis, pharyngitis, ear infection, oral candidiasis, catheter-related infection, bronchiolitis, nasopharyngitis, diarrhea, vomiting, gastroesophageal reflux disease, constipation, rash, diaper dermatitis, urticaria, tachycardia, bradycardia, post-procedural pain, anemia, flushing.1

Advice to Patients

  • Importance of encouraging caregivers and patients, including nursing women and women of childbearing potential, to participate in the Pompe disease registry (http://www.pomperegistry.com or 800-745-4447).1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.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.)

What are some things I need to know or do while I take Alglucosidase Alfa?

  • Tell all of your health care providers that you take alglucosidase alfa. This includes your doctors, nurses, pharmacists, and dentists.
  • If you will be getting anesthesia, talk with your doctor. The chance of a heartbeat that is not normal and sudden death caused by heart problems may be raised in some people.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • Have your urine checked as you have been told by your doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

Pronunciation

(al gloo KOSE i dase AL fa)

Pharmacology

Alglucosidase alfa is a recombinant form of the enzyme acid alpha-glucosidase (GAA), which is required for glycogen cleavage. Due to an inherited GAA deficiency or absence, glycogen accumulates in the tissues of patients with Pompe disease, leading to progressive muscle weakness. In infantile-onset Pompe disease, glycogen accumulates in cardiac and skeletal muscles and hepatic tissue, leading to cardiomyopathy and respiratory failure. Juvenile- and adult-onset Pompe disease are limited to glycogen accumulation in skeletal muscle, leading to respiratory failure. Alglucosidase alfa binds to mannose-6-phosphate receptors on the cell surface, is internalized, and transported to lysosomes where it is activated for increased enzymatic glycogen cleavage.

Distribution

Vss: Infants 1 to 7 months: 96 ± 16 mL/kg

Half-Life Elimination

Infants 1 to 7 months: 2.3 hours; Adults: 2.4 hours

Special Populations Note

Antibody formation: Higher mean clearance (50%) was observed in patients who tested positive for antibodies to alglucosidase alfa.

Use Labeled Indications

Pompe disease: For use in patients with Pompe disease (acid alpha-glucosidase [GAA] deficiency).

Limitations of use: Myozyme: Improves ventilator-free survival in patients with infantile-onset Pompe disease compared with an untreated historical control, whereas use of Myozyme in patients with other forms of Pompe disease has not been adequately studied to ensure safety and efficacy.

Drug Interactions

There are no known significant interactions.

What is alglucosidase alfa (lumizyme, myozyme)?

Alglucosidase alfa contains an enzyme that naturally occurs in the body in healthy people. Some people lack this enzyme because of a genetic disorder. Alglucosidase alfa helps replace this missing enzyme in such people.

Alglucosidase alfa is used to treat a glycogen storage disorder called Pompe disease, (also called GAA deficiency) in adults and children who are at least 8 years old.

Alglucosidase alfa may also be used for purposes not listed in this medication guide.

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