General Articles

Alglucosidase alfa

Sound-alike/look-alike issues:
Alglucosidase alfa may be confused with agalsidase alfa, agalsidase beta, alglucerase

Myozyme® Shortage – January 2009

Inventory levels of Myozyme® (alglucosidase alfa) are low because of increased global demand. Increased production is planned once regulatory agencies throughout the world approve a larger scale manufacturing process. In the U.S., the Food and Drug Administration (FDA) is expected to respond by the end of February. In the meantime, recommended guidelines have been developed to help with clinical decisions during this temporary period of supply constraint. Pediatric dosing regimens will be maintained. However, to continue providing therapy to adult patients, adult regimens will be adjusted by increasing the dosing interval. Children with newly-diagnosed disease may begin therapy, but no new adults will be enrolled in the Myozyme® Temporary Access Program (MTAP). Any physician who feels their patient is in urgent need of therapy may contact Genzyme Medical Information at (800) 745-4447, option 2.

Additional information may be found at:

U.S. BRAND NAMES — Myozyme®


DOSING: PEDIATRIC — Replacement therapy for Pompe disease (infantile onset): Children 1 month to 3.5 years (at first infusion): I.V.: 20 mg/kg over ~4 hours every 2 weeks

(For additional information see “Alglucosidase alfa: Pediatric drug information”)

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution [preservative free]:
Myozyme®: 50 mg [contains mannitol 210 mg; polysorbate 80; derived from Chinese hamster ovary cells]

Injection, powder for reconstitution [preservative free]:
Myozyme®: 50 mg


ADMINISTRATION — Infuse over ~4 hours; initiate at 1 mg/kg/hour. If tolerated, increase by 2 mg/kg/hour every 30 minutes to a maximum rate of 7 mg/kg/hour. Decrease rate or temporarily hold for infusion reactions. Infuse through a low protein-binding, 0.2 micron in-line filter.

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COMPATIBILITY — Stable in NS; do not infuse with other products.

USE — Replacement therapy for Pompe disease (infantile onset)

Cardiovascular: Tachycardia (23%), bradycardia (21%), flushing (21%)
Central nervous system: Fever (92%), pain (postprocedural: 26%)
Dermatologic: Rash (54%), diaper dermatitis (36%), urticaria (21%)
Gastrointestinal: Diarrhea (62%), vomiting (49%), gastroenteritis (41%), oral candidiasis (31%), gastroesophageal reflux (26%), constipation (23%)
Hematologic: Anemia (31%)
Local: Catheter-related infections (28%)
Otic: Otitis media (33% to 44%)
Respiratory: Cough (46%), pneumonia (46%), upper respiratory tract infection (44%), oxygen saturation decreased (41%), pharyngitis (36%), respiratory distress (33%), respiratory failure (31%), rhinorrhea (28%), bronchiolitis (23%), nasopharyngitis (23%), tachypnea (23%)
Miscellaneous: Antibodies to alglucosidase alfa (89%; may affect efficacy), infusion reaction (51%)

Frequency not reported and/or case reports: Abdominal pain, agitation, anaphylactic reactions, bronchospasm, cardiac arrest, cardiorespiratory failure, chest discomfort/pain, conjunctivitis, cyanosis, erythema, face edema, facial erythema, fatigue, fluid overload, headache, hyperhidrosis, hypersensitivity, hyper-/hypotension, irritability, lacrimation increased, livedo reticularis, malaise, muscle spasm, nausea, pallor, periorbital edema, peripheral edema, pruritus, respiratory syncytial virus infection, restlessness, retching, rhinitis, rigors, skin lesions (ulcerative/necrotizing), tremor, wheezing

CONTRAINDICATIONS — There are no contraindications listed in the manufacturer’s labeling.

Boxed warnings: Anaphylaxis/hypersensitivity reactions: See “Concerns related to adverse effects” below. Cardiovascular disease: See “Disease-related concerns” below. Respiratory disease: See “Disease-related concerns” below.

Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: [U.S. Boxed Warning]: Severe hypersensitivity reactions, including anaphylactic reactions and anaphylactic shock have been reported during and within 3 hours after infusion. Immediate medical support should be readily available. Immune-mediated reactions: Severe immune-mediated reactions (eg, ulcerative and necrotizing skin lesions, type-III immune complex-mediated reactions, inflammatory arthropathy) have occurred up to 3 years after initiation of therapy; monitor for development. Infusion reactions: Infusion-related reactions are common; discontinue immediately for severe hypersensitivity or anaphylactic reaction; mild-to-moderate reactions may be managed by reducing the infusion rate and/or administering antihistamines and/or antipyretics. Appropriate medical support for the management of infusion reactions should be readily available. Use caution with subsequent infusions; infusion reactions have occurred despite premedication with antihistamines, antipyretics, and/or steroids. Patients with acute underlying illness are at greater risk for infusion reactions, including cardiorespiratory failure.

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Disease-related concerns: Cardiovascular disease: [U.S. Boxed Warning]: Use with caution in patients with compromised cardiac function; risk of acute cardiorespiratory failure secondary to infusion-related reactions may be increased. Additional monitoring is warranted. Cardiorespiratory failure has been observed in patients with cardiac hypertrophy up to 72 hours after infusion; arrhythmias have also been observed in patients with cardiac hypertrophy. Pompe disease: Safety and efficacy have not been established in juvenile-onset and adult-onset Pompe disease. Patients with Pompe disease are at increased risk for infusion-related cardiorespiratory failure (possibly due to fluid overload); monitor closely during infusion. Respiratory disease: [U.S. Boxed Warning]: Use with caution in patients with compromised respiratory function; risk of acute cardiorespiratory failure secondary to infusion-related reactions may be increased. Additional monitoring is warranted.

Other warnings/precautions: Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment; patients should be encouraged to register ( or 1-800-745-4447).

DRUG INTERACTIONS — There are no known significant interactions.


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PREGNANCY IMPLICATIONS — Animal studies have not demonstrated teratogenicity or fertility impairment. There are no adequate and well-controlled studies in pregnant women. A registry has been established for Pompe patients; women of childbearing potential are encouraged to enroll in the registry ( or 1-800-745-4447).

LACTATION — Excretion in breast milk unknown/use caution

BREAST-FEEDING CONSIDERATIONS — A registry has been established for Pompe patients; women who are nursing are encouraged to enroll in the registry ( or 1-800-745-4447)

MONITORING PARAMETERS — Liver enzymes (baseline and periodically; elevation may be due to disease process); vital signs during and following infusion; volume overload

The manufacturer recommends monitoring for IgG antibody formation every 3 months. No commercial tests are available; however, sampling kits can be obtained by contacting Genzyme Corporation at 1-800-745-4447.


ozyme (AT, BE, BG, CH, CZ, DE, DK, ES, FI, FR, GB, GR, HK, HN, IE, IL, IT, NL, NO, PT, RU, SE, TR, TW)

MECHANISM OF ACTION — 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, 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, becomes internalized and transported to lysosomes resulting in increased enzymatic activity and glycogen cleavage.

Distribution: Vss: 80-147 mL/kg

Half-life elimination: 2-3 hours