Pronunciation: AL-gloo-KOE-si-dase AL-fa
- Injection, lyophilized powder for solution 50 mg
- Injection, lyophilized powder for solution 50 mg
Exogenous source of acid alpha-glucosidase.
Following a single IV infusion of Myozyme 20 mg/kg, C max and AUC were 162 mcg/mL and 811 mcg•h/mL, respectively. At a steady state, the C max and AUC of Lumizyme 20 mg/kg every other week were 372 mcg/mL and 2,700 mcg•h/mL, respectively.
Following a single IV infusion of Myozyme 20 mg/kg, Cl and half-life were 25 mL/h/kg and 2.3 h, respectively. At steady state, the Cl and half-life of Lumizyme 20 mg/kg every other week were 601 mL/h and 2.4 h, respectively.
Special PopulationsAntibody formation
Higher mean Cl (42% to 50%) was observed in patients who tested positive for antibodies to alglucosidase alfa.
Indications and Usage
Treatment of infantile-onset Pompe disease ( Myozyme ); treatment of late-onset Pompe disease ( Lumizyme ).
None well documented.
Dosage and AdministrationAdults and Children
IV 20 mg/kg administered by IV infusion over approximately 4 h every 2 wk. Administer in a step-wise manner, starting with no more than 1 mg/kg/h. The infusion rate may be increased by 2 mg/kg/h every 30 min after tolerance to infusion rate is established (max rate, 7 mg/kg/h).
- Obtain vital signs at the end of each step of dose titration.
- Slow or temporarily stop the infusion in the event of an infusion reaction.
- Because alglucosidase alfa does not contain preservatives, vials are single-use only; discard unused portion.
- Remove required number of vials from the refrigerator and allow to reach room temperature (59° to 86°F) for approximately 30 min prior to reconstitution.
- Reconstitute each vial by slowly injecting 10.3 mL of sterile water for injection, which will yield 5 mg/mL.
- Protect reconstituted solution from light.
- Perform an immediate inspection of reconstituted vials for particulate matter and discoloration. Do not use discolored solution. Reconstituted solution may contain some alglucosidase alfa particles in the form of thin, white strands or translucent fibers. These particles are removed by inline filtration without affecting purity or strength.
- Immediately dilute reconstituted solution with sodium chloride 0.9% for injection to a final concentration of 0.5 to 4 mg/mL.
- Slowly withdraw reconstituted solution to avoid foaming in syringe.
- Remove airspace from infusion bag to minimize particle formation and add reconstituted alglucosidase solution slowly and directly into sodium chloride solution. Avoid foaming in the infusion bag.
- Gently invert or massage infusion bag to mix. Do not shake.
- Filter diluted solution through a 0.2 mcm, low-protein-binding, in-line filter during administration to remove any visible particles.
- Do not infuse in the same IV line with other products.
Refrigerate between 36° and 46°F. Administer reconstituted and diluted solution without delay. If immediate use is not possible, reconstituted and diluted solution is stable for up to 24 h at 36° to 46°F. Protect from light. Do not freeze or shake.
None well documented.
Tachycardia (23%); bradycardia (21%); cardiac arrest (postmarketing).
Pyrexia (92%); tremor, vertigo (7%); malaise, somnolence (5%).
Rash (54%); diaper dermatitis (36%); flushing, urticaria (21%); pruritus (10%); hyperhidrosis (8%); systemic and cutaneous immune-mediated reactions including necrotizing skin lesions (postmarketing).
Otitis media (44%); pharyngitis (36%); ear infection, hypoacusis (33%); nasopharyngitis (23%); ear pain or discomfort (12%); blurred vision, epistaxis (5%).
Diarrhea (62%); vomiting (49%); gastroenteritis (41%); oral candidiasis (31%); gastroesophageal reflux disease (26%); constipation (23%); dyspepsia (8%).
Anaphylaxis (7%); anaphylactic shock (postmarketing).
Positive test for immunoglobulin G (IgG) antibodies (89%); decreased oxygen saturation (41%).
Catheter-related infection (28%); infusion-site reactions (13%).
Peripheral edema (17%); hypokalemia (5%).
Musculoskeletal pain (37%); musculoskeletal stiffness or tightness (15%); muscle twitching (8%).
Cough, pneumonia (46%); upper respiratory tract infection (44%); respiratory distress (33%); respiratory failure (31%); rhinorrhea (28%); bronchiolitis, tachypnea (23%); exertional dyspnea (7%); respiratory tract infection (5%).
Infusion reactions (51%); postprocedural pain (26%); chest pain or discomfort (17%); procedural pain (15%); lymphadenopathy, pain (8%); aortic dissection, cardiac failure, cardiorespiratory arrest, cerebrovascular accident, hemothorax, pneumothorax, respiratory failure, sepsis, and skin necrosis, all possibly resulting in death (postmarketing).
Life-threatening anaphylactic reactions, severe allergic reactions, and immune-mediated reactions have been observed in patients during alglucosidase alfa infusion. Appropriate medical support measures should be readily available.Cardiorespiratory failure
Patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise because of infusion reactions; these patients require additional monitoring.Lumizyme restricted distribution
Because of the potential risk of rapid disease progression of Pompe disease in patients younger than 8 years of age, Lumizyme is available only through a restricted distribution program ( Lumizyme ACE Program). Only prescribers and health care facilities enrolled in the program may prescribe, dispense, or administer Lumizyme . Patients must also be enrolled and meet all of the conditions of the program.
Monitor patients for the development of systemic immune complex–mediated reactions involving skin and other organs. Monitor patients for IgG antibody formation every 3 mo for 2 y and then annually thereafter. Evaluate liver enzymes prior to initiation of treatment and periodically thereafter. Monitor vital signs at the end of each infusion rate increase.
Category B .
Safety and efficacy of Myozyme not established in juvenile-onset Pompe disease. Lumizyme is not for use in infantile-onset Pompe disease or late-onset Pompe disease in patients younger than 8 y of age.
Patients with an acute underlying illness at the time of infusion appear to be at greater risk for infusion reactions.
Cardiac arrhythmia, including bradycardia, ventricular fibrillation, and ventricular tachycardia, resulting in cardiac arrest or defibrillation has occurred. These events were in patients with infantile-onset Pompe disease with cardiac hypertrophy, and associated with general anesthesia used for placement of central venous catheter for alglucosidase infusion.
Acute cardiorespiratory failure requiring intubation and inotropic support has been observed after infusion with alglucosidase. Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at increased risk.
Severe cutaneous and systemic immune-mediated reactions, including ulcerative and necrotizing skin lesions, and possible type III immune complex–mediated reactions, may occur.
Antibodies to alglucosidase alfa may develop, usually within the first 3 mo of exposure. There is evidence that some patients who develop high and sustained antibody titers may have a poorer clinical response.
Severe infusion reactions may occur and may be managed with administration of antihistamines, corticosteroids, IV fluids, and/or oxygen, when clinically indicated.
No reports of overdosage.
- Inform patient and caregiver that a registry for patients with Pompe disease has been established to better understand the variability and progression of the disease and monitor and evaluate treatment.
- Inform patient and caregiver that patient must be enrolled in and meet all of the terms of the Lumizyme ACE Program to receive the medication.
- Inform patient and caregiver that infusion reactions may occur during or within 2 h of completion of the infusion.
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