Alglucosidase Alfa

Trade Names:Myozyme- Powder for injection 50 mg

Pharmacology

Exogenous source of alpha-glucosidase (GAA).

Pharmacokinetics

Absorption

Following a single IV infusion of 20 mg/kg, C _max and AUC were 162 mcg/mL and 811 mcg•h/mL, respectively.

Elimination

Following a single IV infusion of 20 mg/kg, Cl and t _½ were 25 mL/h/kg and 2.3 h, respectively.

Indications and Usage

Treatment of Pompe disease (GAA deficiency).

Contraindications

Standard considerations.

Dosage and Administration

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).

General Advice

• 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 on 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, inline filter during administration to remove any visible particles.
• Do not infuse in the same IV line with other products.

Storage/Stability

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.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Tachycardia (23%); bradycardia (21%).

CNS

Pyrexia (92%).

Dermatologic

Rash (54%); diaper dermatitis (36%); urticaria (23%); flushing (21%).

EENT

Otitis media (44%); pharyngitis (36%); ear infection (33%); nasopharyngitis (23%).

GI

Diarrhea (62%); vomiting (49%); gastroenteritis (41%); oral candidiasis (31%); gastroesophageal reflux disease (26%); constipation (23%).

Hematologic-Lymphatic

Anemia (31%).

Lab Tests

Positive test for immunoglobulin G antibodies (89%); decreased oxygen saturation (41%).

Local

Catheter-related infection (28%).

Respiratory

Cough, pneumonia (46%); upper respiratory tract infection (44%); respiratory distress (33%); respiratory failure (31%); rhinorrhea (28%); bronchiolitis, tachypnea (23%).

Miscellaneous

Infusion reactions (51%); postprocedural pain (26%).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established in juvenile-onset Pompe disease population.

Cardiac arrhythmia

Cardiac arrhythmia, including bradycardia, ventricular fibrillation, and ventricular tachycardia, resulting in cardiac arrest or defibrillation has occurred. These events were in infantile-onset Pompe disease patients with cardiac hypertrophy, associated with general anesthesia used for placement of central venous catheter for alglucosidase infusion.

Cardiorespiratory failure

Acute cardiorespiratory failure requiring intubation and inotropic support has been observed after infusion with alglucosidase.

Infusion reactions

Severe infusion reactions may occur.

Overdosage

Symptoms

No reports of overdosage.

Patient Information

• 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.

Copyright © 2009 Wolters Kluwer Health.