Alglucosidase alfa

U.S. BRAND NAMES — Myozyme®
PHARMACOLOGIC CATEGORY Enzyme
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
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]
DOSAGE FORMS: CONCISE Injection, powder for reconstitution [preservative free]: Myozyme®: 50 mg
GENERIC EQUIVALENT AVAILABLE — No
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.
COMPATIBILITY — Stable in NS; do not infuse with other products.
USE — Replacement therapy for Pompe disease (infantile onset)
ADVERSE REACTIONS SIGNIFICANT >20%: 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: Infusion reaction (51%)
Frequency not reported and/or case reports: Abdominal pain, agitation, anaphylactic reactions, bronchospasm, cardiorespiratory failure, cyanosis, erythema, face edema, facial erythema, fluid overload, headache, hyperhydrosis, hypersensitivity, hyper-/hypotension, irritability, lacrimation increased, livedo reticularis, malaise, nausea, pallor, periorbital edema, pruritus, respiratory syncytial virus infection, restlessness, retching, rhinitis, rigors, tremor, wheezing
CONTRAINDICATIONS — Hypersensitivity to alglucosidase alfa or any component of the formulation
WARNINGS / PRECAUTIONS Concerns related to adverse effects: Anaphylaxis/hypersensitivity/infusion reactions: Severe hypersensitivity reactions, including anaphylactic reactions and anaphylactic shock have been reported during infusion. 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.
Disease-related concerns: Cardiovascular disease: Use with caution in patients with cardiovascular disease. 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: Use with caution in patients with respiratory disease.
PREGNANCY RISK FACTOR — B (show table)
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 (www.pomperegistry.com 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 (www.pomperegistry.com 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
TOXICOLOGY / OVERDOSE COMPREHENSIVE — There have been no reports of overdose. Doses of up to 40 mg/kg were administered in clinical trials. Treatment of overdose is symptom-directed and supportive.
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.
PHARMACODYNAMICS / KINETICS Distribution: Vss: 80-112 mL/kg
Half-life elimination: 2.3 hours