(al gloo KOSE i dase AL fa)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Lumizyme: 50 mg (1 ea) [contains polysorbate 80]
Myozyme: 50 mg (1 ea)
Brand Names: U.S.
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.
Vss: Infants 1 to 7 months: 96 ± 16 mL/kg
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.
There are no contraindications listed in the manufacturer’s labeling.
Pompe disease: IV:
Infantile-onset (Lumizyme, Myozyme): Infants ≥1 month, Children, and Adolescents: 20 mg/kg every 2 weeks
Noninfantile, late-onset (Lumizyme): Infants ≥1 month, Children, Adolescents, and Adults: 20 mg/kg every 2 weeks
Dosage adjustment in renal impairment: There are no dosage adjustments provided in the manufacturer’s labeling.
Dosage adjustment in hepatic impairment: There are no dosage adjustments provided in the manufacturer’s labeling.
Allow vials to reach room temperature prior to reconstitution (~30 minutes). Reconstitute each vial with 10.3 mL of SWFI. Inject slowly down internal side wall of vial (do not inject into powder; avoid foaming). Roll and tilt gently; do not invert, swirl, or shake. Resulting solution contains 5 mg/mL. To make final infusion, add the desired amount of reconstituted solution (based on patient weight) to 50 to 1000 mL of NS (do not use filter needle to prepare) to a final concentration of 0.5 to 4 mg/mL. Remove airspace from infusion bag prior to admixture to minimize particle formation due to sensitivity of drug to air-liquid interfaces. Gently invert or massage infusion bag to mix; do not shake.
Infuse through a low-protein-binding, 0.2 micron in-line filter. 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 mild to moderate infusion reactions. Monitor vital signs prior to each rate increase. Protect from light.
Stable in NS; do not infuse with other products.
Store intact vials between 2°C and 8°C (36°F and 46°F). Final solutions for infusion should be used immediately if possible but may be stored for up to 24 hours between 2°C and 8°C (36°F and 46°F); do not freeze. Protect from light.
There are no known significant interactions.
Cardiovascular: Oxygen saturation decreased (infants and children 8% to 41%), tachycardia (infants and children 8% to 23%), bradycardia (infants and children 21%), flushing (5% to 21%), chest pain (17%), peripheral edema (3% to 17%)
Central nervous system: Pain (postprocedural; infants and children 26%; adults 15%)
Dermatologic: Skin rash (infants and children 18% to 54%; adults ≥3%), diaper rash (infants and children 36%), urticaria (8% to 21%)
Gastrointestinal: Diarrhea (infants and children 62%; adults ≥3%), vomiting (infants and children 5% to 49%; adults 5% to 22%), gastroenteritis (infants and children 41%; adults 10%), oral candidiasis (infants and children 31%), gastroesophageal reflux disease (infants and children 26%), constipation (infants and children 23%; adults 10%), upper abdominal pain (children and adolescents 15%)
Hematologic & oncologic: Anemia (infants and children 31%)
Hypersensitivity: Hypersensitivity reaction (infants and children 51%)
Immunologic: Development of IgG antibodies (adults 100%; infants and children 89%; may affect efficacy)
Local: Catheter infection (infants and children 28%), infusion site reaction (13%)
Neuromuscular & skeletal: Musculoskeletal pain (37%), stiffness (15%)
Otic: Otitis media (infants and children 33% to 44%), auditory impairment (33%), otalgia (12%)
Respiratory: Cough (infants and children 8% to 46%), pneumonia (infants and children 46%), upper respiratory tract infection (infants and children 44%; adults 18%), pharyngitis (infants and children 36%; children and adolescents 9%), respiratory distress (infants and children 33%), respiratory failure (infants and children 31%), rhinorrhea (infants and children 28%), bronchiolitis (infants and children 23%), nasopharyngitis (infants and children 23%), tachypnea (infants and children 8% to 23%), respiratory syncytial virus infection (infants and children >10%)
Miscellaneous: Fever (infants and children 15% to 92%), infusion related reaction (infants and children 51%)
1% to 10%:
Cardiovascular: Hypertension (infants and children 10%), chest discomfort (7%), increased blood pressure (5%)
Central nervous system: Pain (8%), vertigo (7%), malaise (5% to 6%), dizziness (≥5%), fatigue (≥5%), headache (≥5%), agitation (infants and children 5%), drowsiness (5%), rigors (infants and children 5%), paresthesia (≥3%)
Dermatologic: Pruritus (10%), hyperhidrosis (8%), erythema (infants and children 5%), pallor (infants and children 5%), papular rash (3%)
Endocrine & metabolic: Hypokalemia (5%)
Gastrointestinal: Dyspepsia (8%), nausea (≥5%)
Hematologic & oncologic: Lymphadenopathy (8%)
Hypersensitivity: Anaphylaxis (7%)
Local: Local swelling (≥3%)
Neuromuscular & skeletal: Muscle twitching (7% to 8%), tremor (5% to 7%), myalgia (5%)
Ophthalmic: Blurred vision (5%)
Renal: Nephrolithiasis (5%)
Respiratory: Dyspnea (7%), rhinitis (children and adolescents 6%), cyanosis (≥5%), epistaxis (5%), respiratory tract infection (5%), pharyngeal edema (3%)
<1% (Limited to important or life-threatening): Acute cardiorespiratory failure, aortic dissection, apnea, bronchospasm, cerebrovascular accident, convulsions, coronary artery disease, dehydration, flu-like symptoms, hemothorax, herniated disk, hyperparathyroidism, hypersensitivity, hypervolemia, livedo reticularis, muscle spasm, nephrotic syndrome (secondary to membranous glomerulonephritis), nodal arrhythmia, periorbital edema, pneumothorax, pulmonary infection, sepsis, skin necrosis, ventricular premature contractions
Concerns related to adverse effects:
• IgG antibody formation: The presence of IgG antibodies has been observed within 3 months from the onset of therapy in the majority of patients. High and sustained IgG antibody titers may result in reduced efficacy of alglucosidase alfa (eg, loss of motor function, ventilator dependence, death). Regularly monitor all patients for development of IgG antibodies; consider testing for IgG titers in patients who develop hypersensitivity reactions, other immune-mediated reactions, or loss of clinical response. Patients with reduced clinical response may also be tested for inhibitory antibody activity.
• Hypersensitivity/anaphylactoid reactions: [U.S. Boxed Warning]: Life-threatening anaphylactic reactions and severe hypersensitivity reactions, some of which were IgE mediated, may occur; immediate medical support should be readily available. Reactions may occur during and up to 3 hours after infusion. Patients who develop IgE antibodies to alglucosidase alfa may be at a higher risk; monitor these patients closely during administration. Consider testing for IgG titers in patients who develop allergic reactions; may also test for IgE antibodies or other mediators of anaphylaxis. Consider risks/benefits of readministration following an anaphylactic or severe allergic reaction; some patients have been rechallenged under close clinical supervision; appropriate resuscitation measures should be available.
• Immune-mediated adverse effects: [U.S. Boxed Warning]: Severe immune-mediated reactions (eg, necrotizing skin lesions, nephrotic syndrome secondary to membranous glomerulonephritis, proteinuria, inflammatory arthropathy) may occur; immediate medical support should be readily available. Reactions have occurred up to 3 years after initiation of therapy. Monitor urinalysis periodically. Monitor for immune-mediated reaction development. Consider testing for IgG titers in patients who develop immune-mediated reactions; may also test for IgE antibodies. Consider risks/benefits of readministration; some patients have been successfully rechallenged under close clinical supervision.
• Infusion reactions: Infusion-related reactions are common and may occur during and up to 2 hours after infusion. Appropriate medical support for the management of infusion reactions should be readily available. 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. Use caution with subsequent infusions; infusion reactions have occurred despite premedication with antihistamines, antipyretics, and/or corticosteroids. Patients with acute underlying illness are at greater risk for infusion reactions, including cardiorespiratory failure; monitor closely during infusion. Although less common, delayed-onset (within 48 hours after administration) infusion reactions have also occurred.
• 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 or fluid overload 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.
• 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 or fluid overload may be increased. Additional monitoring is warranted.
• Sepsis: Patients with sepsis may be at increased risk for cardiorespiratory failure during infusions.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley, 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade, 1986; CDC, 1984). See manufacturer’s labeling.
• Anesthesia: Use of general anesthesia for catheter placement for alglucosidase alfa infusions may be complicated by the presence of cardiac and skeletal (including respiratory) muscle weakness in patients with Pompe disease; use general anesthesia with caution.
• Registry: A registry has been created to monitor therapeutic responses and adverse effects during long-term treatment; patients should be encouraged to register (www.pomperegistry.com or 1-800-745-4447).
Liver enzymes (baseline and periodically; elevation may be due to disease process); vital signs (prior to each infusion rate increase) during and following infusion; immune-mediated reactions; volume overload; urinalysis (periodically)
The manufacturer recommends monitoring for IgG antibody formation every 3 months for 2 years, then annually. Consider testing if patient develops allergic or other suspected immune-mediated reaction or experiences loss of clinical response. No commercial tests are available; however, sampling kits can be obtained by contacting Genzyme Corporation at 1-800-745-4447. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. Limited information is available related to use of alglucosidase alfa in pregnant women (deVries 2011).
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).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience constipation, heart burn, tremors, or injection site irritation. Have patient report immediately to prescriber signs of infusion reaction (back pain, bluish skin or nails, numbness, tingling, angina, abnormal heartbeat, flushing, chills, hives, seizures, chest tightness, or wheezing), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of kidney stone (back pain, abdominal pain, blood in urine), signs of breathing problems (shortness of breath, wheezing, coughing, or breathing gets worse), excessive weight gain, swelling of arm or leg, abnormal heartbeat, agitation, myoclonus, diaphoresis, abnormal heartbeat, muscle rigidity, restlessness, neck pain, ear pain, hearing impairment, nosebleed, skin changes, watery eyes, loss of strength and energy, vision changes, redness or white patches in mouth or throat, or enlarged lymph nodes (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.