Lumizyme

Alglucosidase Alfa · Injection, Powder, For Solution · Intravenous

Prescription (Rx) Hydrolytic Lysosomal Glycogen-specific Enzyme 1 recall

Boxed warning. WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS, IMMUNE-MEDIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE WARNING: HYPERSENSITIVITY REACTIONS INCLUDING ANAPHYLAXIS, IMMUNE-MEDIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE See full prescribing information for complete boxed warning. Hypersensitivity Reactions Including Anaphylaxis Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate LUMIZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue LUMIZYME and immediately initiate appropriate medical treatment, including use of epinephrine. ( 5.1 ) Immune-Mediated Reactions Immune-mediated reactions presenting as…

Uses

1 INDICATIONS AND USAGE LUMIZYME ® is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (acid α-glucosidase [GAA] deficiency). LUMIZYME ® is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (GAA deficiency). ( 1 )

Dosage and administration

Administration of LUMIZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. ( 2.1 ) Recommended dosage is 20 mg/per kg body weight administered every 2 weeks as an intravenous infusion. The initial infusion rate should be no more than 1 mg/kg/hour ( 2.2 ) Reconstitute and dilute LUMIZYME prior to use. ( 2.3 ) See full prescribing information for storage of the reconstituted and diluted product and administration instructions ( 2.4 , 2.5 ) 2.1 Recommendations prior to LUMIZYME Treatment Administration of LUMIZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.1) ] . Initiate LUMIZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1) ] . Prior to LUMIZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions (5.1 , 5.2) ] . LUMIZYME must be reconstituted and diluted prior to use [see Dosage and Administration (2.3) ] . Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during LUMIZYME administration [see Warnings and Precautions (5.1) ] . 2.2 Recommended Dosage and Administration The recommended dosage of LUMIZYME is 20 mg/kg body weight administered every 2 weeks as an intravenous infusion. The initial infusion rate should be no more than 1 mg/kg/hour [see Dosage and Administration (2.5) ] . Missed Dose If one or more doses are missed, restart LUMIZYME treatment as soon as possible, maintaining the 2-week interval between infusions thereafter. 2.3 Reconstitution and Dilution Instructions Reconstitute and dilute LUMIZYME in the following manner. Use aseptic technique during preparation. Do not use filter needles during preparation. Reconstitute the Lyophilized Powder Determine the number of LUMIZYME vials to be reconstituted based on the actual body weight in kg and the recommended dose of 20 mg/kg. Round the number of vials up to the next whole number. Remove the required number of LUMIZYME vials from the refrigerator and allow the vials to sit for approximately 30 minutes at room temperature 20°C to 25°C (68°F to 77°F) prior to reconstitution. Reconstitute each vial by slowly injecting 10.3 mL of Sterile Water for Injection, down the inside wall of each vial. Avoid adding the Sterile Water for Injection to the vial forcefully or directly onto the lyophilized powder to minimize foaming. Gently tilt and roll each vial. Do not invert, swirl, or shake the vial. Each vial will yield a concentration of 5 mg/mL of LUMIZYME. The total extractable dose per vial is 50 mg per 10 mL. Visually inspect the reconstituted solution in the vials for particulate matter and discoloration. Discard if particles are present or the solution is discolored. The reconstituted solution may occasionally contain some LUMIZYME particles (typically less than 10 in a vial) in the form of thin white strands or translucent fibers subsequent to the initial inspection. This may also happen following dilution for infusion. These particles have been shown to contain LUMIZYME and may appear after the initial reconstitution step and increase over time. Studies have shown that these particles are removed via in-line filtration without having a detectable effect on the purity or strength. Dilute the Reconstituted Solution Select and prepare an appropriate size 0.9% Sodium Chloride for Injection infusion bag with quantity sufficient of 0.9% Sodium Chloride for Injection to obtain the recommended total infusion volume per table 1 based on patient weight and dilute. Slowly withdraw the required volume of reconstituted solution from the LUMIZYME vial(s). Avoid foaming in the syringe. Discard any unused reconstituted solution remaining in the vial. Remove airspace from the prepared 0.9% Sodium Chloride for Injection infusion bag to minimize particle formation due to the sensitivity of LUMIZYME to air-liquid interfaces. Inject the LUMIZYME reconstituted solution slowly and directly into the port of the prepared 0.9% Sodium Chloride for Injection infusion bag. Avoid foaming and introducing air in the infusion bag. Gently invert or massage the infusion bag to mix the solution. Do not shake. After dilution, the solution will have a final concentration of 0.5 to 4 mg/mL of LUMIZYME. 2.4 Storage Instructions for the Reconstituted and Diluted Product The reconstituted and diluted solution should be administered without delay. Storage of the reconstituted solution at room temperature is not recommended. If immediate use is not possible, the reconstituted and diluted solution is stable for up to 24 hours refrigerated at 2°C to 8°C (36°F to 46°F). The reconstituted and diluted LUMIZYME solution should be protected from light. Do not freeze or shake. 2.5 Administration Instructions The total volume of infusion is determined by the patient's body weight and should be administered over approximately 4 hours. Administer LUMIZYME using an in-line low protein binding 0.2-micron filter. Infusions should be administered in a step-wise manner using an infusion pump. The initial infusion rate should be no more than 1 mg/kg/hr. The infusion rate may be increased by 2 mg/kg/hr every 30 minutes, after patient tolerance to the infusion rate is established, until a maximum rate of 7 mg/kg/hr is reached. Vital signs should be obtained at the end of each step. If the patient is stable, LUMIZYME may be administered at the maximum rate of 7 mg/kg/hr until the infusion is completed. The infusion rate may be slowed or temporarily stopped in the event of mild to moderate hypersensitivity reactions.

Dosage forms and strengths

For injection: 50 mg of LUMIZYME is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder in a single-dose vial for reconstitution. After reconstitution, the resultant solution concentration is 5 mg/mL. For injection: 50 mg of LUMIZYME as lyophilized powder in a single-dose vial for reconstitution. ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

Infusion-Associated Reactions (IARs) : If an IAR occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. ( 5.2 ) Risk of Cardiac Arrhythmia and Sudden Cardiac Death during General Anesthesia for Central Venous Catheter Placement : Caution should be used when administering general anesthesia for the placement of a central venous catheter intended for LUMIZYME infusion. ( 5.5 ) Risk of Developing Anti-alglucosidase Alfa Antibodies : Patients with IOPD should have a cross-reactive immunologic material (CRIM) assessment early in their disease course and be managed by a clinical specialist knowledgeable in immune tolerance induction in Pompe disease. ( 5.6 ) 5.1 Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions including anaphylaxis have been observed in patients during and up to 3 hours after a LUMIZYME infusion. Some of the hypersensitivity reactions were life-threatening and included anaphylactic shock, cardiac arrest, respiratory arrest, respiratory distress, hypoxia, apnea, dyspnea, bradycardia, tachycardia, bronchospasm, throat tightness, hypotension, angioedema (including tongue or lip swelling, periorbital edema, and face edema), and urticaria. Other accompanying reactions included chest discomfort/pain, wheezing, tachypnea, cyanosis, decreased oxygen saturation, convulsions, pruritus, rash, hyperhidrosis, nausea, dizziness, hypertension/increased blood pressure, flushing/feeling hot, erythema, pyrexia, pallor, peripheral coldness, restlessness, nervousness, headache, back pain, and paresthesia. Some of these reactions were IgE-mediated. In clinical trials, hypersensitivity reactions including anaphylaxis were managed with infusion interruption; decreased infusion rate; and administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen. In some cases of anaphylaxis, epinephrine was administered. Some LUMIZYME-treated patients who experienced a hypersensitivity reaction and who tested positive for alglucosidase alfa-specific IgE antibodies were successfully rechallenged with a slower infusion rate at a lower dosage of LUMIZYME and continued to receive LUMIZYME under close clinical supervision. Because LUMIZYME-treated patients who develop anti-IgE alglucosidase alfa antibodies appear to be at a higher risk for developing hypersensitivity reactions including anaphylaxis, these patients should be monitored more closely during LUMIZYME administration. Recommendations to Prevent, Mitigate, and Monitor for Hypersensitivity Reactions Prior to LUMIZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Administration of LUMIZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate LUMIZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue LUMIZYME and immediately initiate appropriate medical treatment, including use of epinephrine. If a mild or moderate hypersensitivity reaction occurs, consider temporarily holding the LUMIZYME infusion or slowing the infusion rate. Consider the risks and benefits of readministering LUMIZYME following a hypersensitivity reaction including anaphylaxis. Patients may be rechallenged using slower infusion rates at a lower dosage than the recommended dosage [see Adverse Reactions (6.2) ] . Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and recommend they seek immediate medical care should these symptoms occur. 5.2 Infusion-Associated Reactions Infusion-associated reactions (IARs) such as pyrexia, chills, flu-like illness, myalgia, arthralgia, pain, fatigue, urticaria, rash, pruritus, erythema, dyspnea, tachycardia, flushing, nausea, headache and syncope occurred in LUMIZYME-treated patients [see Adverse Reactions (6.2) ] . If an IAR occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administering antihistamines and/or antipyretics may ameliorate the symptoms. Closely monitor patients who have experienced IARs when re-administering LUMIZYME. 5.3 Immune-Mediated Reactions Immune-mediated cutaneous reactions have been reported with LUMIZYME including necrotizing skin lesions [see Adverse Reactions (6.2) ] . Systemic immune-mediated reactions, including possible type III immune-mediated reactions have been observed with LUMIZYME. These reactions occurred several weeks to 3 years after initiation of LUMIZYME infusions. Skin biopsy in one patient demonstrated deposition of anti-rhGAA antibodies in the lesion. Another patient developed severe inflammatory arthropathy in association with pyrexia and elevated erythrocyte sedimentation rate. Nephrotic syndrome secondary to membranous glomerulonephritis was observed in some LUMIZYME-treated patients with Pompe disease who had persistently positive anti-rhGAA IgG antibody titers. In these patients, renal biopsy was consistent with immune complex deposition. Patients improved following LUMIZYME treatment interruption [see Adverse Reactions (6.2) ] . LUMIZYME treated patients should be monitored for the development of systemic immune-mediated reactions involving skin and other organs including periodic urinalysis. If immune-mediated reactions occur, consider discontinuing the LUMIZYME administration, and initiating appropriate medical treatment. The risks and benefits of readministering LUMIZYME following an immune-mediated reaction should be considered.

Side effects

The following serious adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions (5.1) ] The most frequently reported adverse reactions (≥5%) in clinical trials were hypersensitivity reactions and included: anaphylaxis, rash, pyrexia, flushing/feeling hot, urticaria, headache, hyperhidrosis, nausea, cough, decreased oxygen saturation, tachycardia, tachypnea, chest discomfort, dizziness, muscle twitching, agitation, cyanosis, erythema, hypertension/increased blood pressure, pallor, rigors, tremor, vomiting, fatigue, and myalgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genzyme at 1-800-633-1610, option 1 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In clinical trials, the most common adverse reactions (≥5%) following intravenous alglucosidase alfa treatment were hypersensitivity reactions, and included anaphylaxis, rash, pyrexia, flushing/feeling hot, urticaria, headache, hyperhidrosis, nausea, cough, decreased oxygen saturation, tachycardia, tachypnea, chest discomfort, dizziness, muscle twitching, agitation, cyanosis, erythema, hypertension/increased blood pressure, pallor, rigors, tremor, vomiting, fatigue, and myalgia. Adverse Reactions in Clinical Trials in Infantile-Onset and Juvenile-Onset Pompe Disease Two multicenter, open-label clinical trials (Trials 1 and 2) [see Clinical Studies (14.1) ] were conducted in 39 patients with infantile-onset Pompe disease (IOPD), aged 1 month to 3.5 years old. Approximately half of the patients (54%) were male. Patients were treated with intravenous alglucosidase alfa 20 or 40 mg/kg every other week for periods ranging from 1 to 106 weeks (mean: 61 weeks). The most serious adverse reactions reported with alglucosidase alfa treatment included anaphylaxis and acute cardiorespiratory failure. The most common adverse reactions requiring intervention in these clinical trials were hypersensitivity reactions, that occurred in 20 of 39 (51%) patients treated with alglucosidase alfa, and included rash, pyrexia, urticaria, flushing, decreased oxygen saturation, cough, tachypnea, tachycardia, hypertension/increased blood pressure, pallor, rigors, vomiting, cyanosis, agitation, and tremor. These reactions were more likely to occur with higher infusion rates or doses. Some patients who were pretreated with antihistamines, antipyretics and/or corticosteroids still experienced hypersensitivity reactions. Table 2 summarizes all adverse reactions that occurred in ≥5% of patients (2 or more patients) treated with alglucosidase alfa in clinical trials described above. Table 2: Adverse Reactions that Occurred in at Least 5% of Alglucosidase Alfa-Treated Infantile-Onset Patients in Trials 1 and 2 Number of Patients (N=39) n (%) Adverse Reaction 20 (51) Rash (including rash erythematous, rash macular and maculopapular) 7 (18) Pyrexia 6 (15) Urticaria 5 (13) Flushing 5 (13) Hypertension/Increased Blood Pressure 4 (10) Decreased Oxygen Saturation 3 (8) Cough 3 (8) Tachypnea 3 (8) Tachycardia 3 (8) Erythema 2 (5) Vomiting 2 (5) Rigors 2 (5) Pallor 2 (5) Cyanosis 2 (5) Agitation 2 (5) Tremor 2 (5) An open-label, single-center trial (Trial 3) was conducted in 18 treatment-naive patients with IOPD who were treated with alglucosidase alfa [see Clinical Studies (14.1) ] . Adverse reactions observed in these patients were similar to patients with IOPD who received alglucosidase alfa in other clinical trials. Additional hypersensitivity reactions observed in patients with IOPD treated with alglucosidase alfa in other clinical trials and expanded access programs included livedo reticularis, irritability, retching, increased lacrimation, ventricular extrasystoles, nodal rhythm, rales, respiratory tract irritation, and cold sweat. Safety was also evaluated in 99 patients (51 male, 48 females) with Pompe disease in an ongoing, open-label, prospective study in patients 12 months of age and older who were previously treated with another alglucosidase alfa product and switched to LUMIZYME. Patients were aged 1 to 18 years with a median duration of treatment of 437 days (range 13 to 466 days). No new safety findings were observed following the switch to 4000 L scale of alglucosidase alfa. Adverse Reactions in Clinical Trials in Late-Onset Pompe Disease Assessment of adverse reactions in patients with late-onset Pompe disease (LOPD) is based on the exposure of 90 patients (45 male, 45 female), aged 10 to 70 years, to intravenous infusions of 20 mg/kg alglucosidase alfa or placebo in a randomized, double-blind, placebo-controlled trial (Trial 4). All patients were naive to enzyme replacement therapy. Patients were randomized in a 2:1 ratio and received intravenous alglucosidase alfa or placebo every other week for 78 weeks (18 months). Two patients who received alglucosidase alfa discontinued the trial due to anaphylactic reactions. Serious adverse reactions reported with alglucosidase alfa included anaphylaxis, which presented as angioedema, throat tightness and chest pain/discomfort. One patient with a history of Wolff-Parkinson-White syndrome experienced a serious adverse reaction of supraventricular tachycardia. The most common adverse reactions (≥3%; 2 or more patients) observed in alglucosidase alfa-treated patients were hypersensitivity reactions and included anaphylaxis, headache, nausea, urticaria, dizziness, chest discomfort, vomiting, hyperhidrosis, flushing/feeling hot, increased blood pressure, paresthesia, pyrexia, local swelling, diarrhea, pruritus, rash, and throat tightness.

Use in specific populations

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LUMIZYME during pregnancy. Pregnant women and women of reproductive potential should be encouraged to enroll in the Pompe patient registry. The registry will monitor the effect of LUMIZYME on pregnant women and their offspring. For more information, visit www.registrynxt.com or call 1-800-745-4447, extension 15500. Risk Summary Data from postmarketing reports and published case reports with alglucosidase alfa use in pregnant women have not identified a LUMIZYME-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The continuation of treatment for Pompe disease during pregnancy should be individualized to the pregnant woman. Untreated Pompe disease may result in worsening disease symptoms in pregnant women (see Clinical Considerations ). Reproduction studies performed in mice and rabbits at doses resulting in exposures up to 0.4 or 0.5 times the human steady-state AUC (area under the plasma concentration-time curve), respectively, during the period of organogenesis revealed no evidence of effects on embryo-fetal development. In mice there was an increase in pup mortality during lactation at maternal exposures 0.4 times the human steady-state AUC (see Data ) . The background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo-fetal Risk Untreated Pompe disease has been associated with worsening respiratory and musculoskeletal symptoms in some pregnant women. Data Animal Data All reproductive studies included pretreatment with diphenhydramine to prevent or minimize hypersensitivity reactions. The effects of alglucosidase alfa were evaluated based on comparison to a control group treated with diphenhydramine alone. Daily intravenous administration of alglucosidase alfa up to 40 mg/kg in mice and rabbits (0.4 and 0.5 times the human steady-state AUC, respectively, at the recommended biweekly dose) during the period of organogenesis had no effects on embryo-fetal development. Administration of 40 mg/kg intravenously every other day in mice (0.4 times the human steady-state AUC at the recommended biweekly dose) during the period of organogenesis through lactation produced an increase in mortality of offspring during the lactation period. 8.2 Lactation Risk Summary Available published literature suggests the presence of alglucosidase alfa in human milk. There are no reports of adverse effects of alglucosidase alfa on the breastfed infant. There is no information on the effects of alglucosidase alfa on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LUMIZYME and any potential adverse effects on the breastfed child from LUMIZYME or from the underlying maternal condition. Lactating women with Pompe disease treated with LUMIZYME should be encouraged to enroll in the Pompe disease registry [see Use in Specific Populations (8.1) ] . Clinical Considerations A lactating woman may consider interrupting breastfeeding, pumping and discarding breast milk during treatment and for 24 hours after LUMIZYME administration in order to minimize drug exposure to a breastfed infant. 8.4 Pediatric Use The safety and effectiveness of LUMIZYME has been established in pediatric patients with Pompe disease [see Adverse Reactions (6.2) ] .The use of LUMIZYME for this pediatric indication is supported by evidence from an adequate and well-controlled trial in 57 treatment-naive pediatric patients with IOPD treated with alglucosidase alfa, aged 0.2 month to 3.5 years at first infusion, (Trials 1, 2, and 3) [see Clinical Studies (14.1) ] and 90 adult and pediatric patients with LOPD in a randomized, double-blind, placebo-controlled trial including 2 patients 16 years of age or less [see Clinical Studies (14.2) ] . Anaphylaxis, hypersensitivity reactions, and acute cardiorespiratory failure have occurred in pediatric patients [see Boxed Warning , Warnings and Precautions (5.1 , 5.3) ] . Additionally, cardiac arrhythmia and sudden cardiac death have occurred in pediatric patients during general anesthesia for central venous catheter placement [see Warnings and Precautions (5.4) ] . 8.5 Geriatric Use The randomized, double-blind, placebo-controlled study of alglucosidase alfa did not include sufficient numbers (n=4) of patients aged 65 years and over to determine whether they respond differently from younger adult patients [see Clinical Studies (14.1) ] .

Pregnancy

Pediatric use

8.4 Pediatric Use The safety and effectiveness of LUMIZYME has been established in pediatric patients with Pompe disease [see Adverse Reactions (6.2) ] .The use of LUMIZYME for this pediatric indication is supported by evidence from an adequate and well-controlled trial in 57 treatment-naive pediatric patients with IOPD treated with alglucosidase alfa, aged 0.2 month to 3.5 years at first infusion, (Trials 1, 2, and 3) [see Clinical Studies (14.1) ] and 90 adult and pediatric patients with LOPD in a randomized, double-blind, placebo-controlled trial including 2 patients 16 years of age or less [see Clinical Studies (14.2) ] . Anaphylaxis, hypersensitivity reactions, and acute cardiorespiratory failure have occurred in pediatric patients [see Boxed Warning , Warnings and Precautions (5.1 , 5.3) ] . Additionally, cardiac arrhythmia and sudden cardiac death have occurred in pediatric patients during general anesthesia for central venous catheter placement [see Warnings and Precautions (5.4) ] .

Geriatric use

8.5 Geriatric Use The randomized, double-blind, placebo-controlled study of alglucosidase alfa did not include sufficient numbers (n=4) of patients aged 65 years and over to determine whether they respond differently from younger adult patients [see Clinical Studies (14.1) ] .

Description

Alglucosidase alfa is a hydrolytic lysosomal glycogen-specific enzyme encoded by the predominant of nine observed haplotypes of the human acid α-glucosidase (GAA) gene. Alglucosidase alfa is produced by recombinant DNA technology in a Chinese hamster ovary cell line. Alglucosidase alfa degrades glycogen by catalyzing the hydrolysis of α-1,4- and α-1,6- glycosidic linkages of lysosomal glycogen. Alglucosidase alfa is a glycoprotein with a calculated mass of 99,377 Daltons for the polypeptide chain, and a total mass of approximately 109,000 Daltons, including carbohydrates. Alglucosidase alfa has a specific activity of 3.6 to 5.4 units/mg (one unit is defined as that amount of activity that results in the hydrolysis of 1 micromole of synthetic substrate per minute under specified assay conditions). Alglucosidase alfa is intended for intravenous infusion. It is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder for reconstitution with 10.3 mL Sterile Water for Injection, USP. Each 50 mg vial contains 52.5 mg alglucosidase alfa, 210 mg mannitol, 0.5 mg polysorbate 80, 9.9 mg sodium phosphate dibasic heptahydrate, and 31.2 mg sodium phosphate monobasic monohydrate. Following reconstitution as directed, each vial contains 10.5 mL reconstituted solution and a total extractable volume of 10 mL at 5 mg/mL alglucosidase alfa. Alglucosidase alfa does not contain preservatives; each vial is for single dose only.

Mechanism of action

12.1 Mechanism of Action Pompe disease (acid maltase deficiency, glycogen storage disease type II, GSD II, glycogenosis type II) is an inherited disorder of glycogen metabolism caused by the absence or marked deficiency of the lysosomal enzyme GAA. Alglucosidase alfa provides an exogenous source of GAA. Binding to mannose-6-phosphate receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen.

How supplied

50 mg vials are supplied as a sterile, nonpyrogenic, preservative-free, white to off-white lyophilized cake or powder in single-dose vials. NDC 58468-0160-1 (Carton of one single-dose vial) NDC 58468-0160-2 (Carton of ten single-dose vials) Store LUMIZYME under refrigeration between 2°C and 8°C (36°F and 46°F). Do not use LUMIZYME after the expiration date on the vial.

Storage

Store LUMIZYME under refrigeration between 2°C and 8°C (36°F and 46°F). Do not use LUMIZYME after the expiration date on the vial.

Patient information

Hypersensitivity Reactions Including Anaphylaxis, Infusion-Associated Reactions (IARs) and Immune-Mediated Reactions Advise the patient and caregiver that life-threatening hypersensitivity reactions, including anaphylaxis, IARs, and immune-mediated reactions may occur with LUMIZYME treatment. Advise the patient and caregiver that anaphylaxis and immune-mediated reactions may occur during the early course of enzyme replacement therapy and after extended duration of therapy. Inform the patient and caregiver of the symptoms of life-threatening hypersensitivity reactions including anaphylaxis, IARs, and immune-mediated reactions and have them seek immediate medical care should these symptoms occur [see Warning and Precautions (5.1 , 5.2 , 5.3) ] . Risk of Acute Cardiorespiratory Failure Advise the patient and caregiver that patients with underlying respiratory illness or compromised cardiac or respiratory function may be at risk of acute cardiorespiratory failure. Patients with compromised cardiac or respiratory function may require close observation during and after alglucosidase alfa administration. Pompe Registry Inform the patient and their caregiver(s) that the Pompe Registry has been established to better understand the variability and progression of Pompe disease, and to continue to monitor and evaluate long-term effects of LUMIZYME on pregnant women and their offspring [see Use in Specific Populations (8.1) ] . Inform the patient and their caregiver(s) that their participation is voluntary and may involve long-term follow-up and to visit www.registrynxt.com or call 1-800-745-4447, extension 15500.

Label text from the FDA structured product label by Genzyme Corporation (revised Jan 10, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Alglucosidase Alfa in 1 product

Lumizyme NDC products (1)

NDC	Strength & form	Labeler	Type
58468-0160	Alglucosidase Alfa 5 mg/mL Injection, Powder, For Solution	Genzyme Corporation	BLA

Lumizyme recalls

D-0799-2016 Apr 6, 2016 · Class III · Terminated
Labeling: Incorrect or Missing Lot and/or Exp Date

Frequently asked questions

What is Lumizyme used for?

What are the side effects of Lumizyme?

Who makes Lumizyme?

Lumizyme is listed by 1 labeler in the FDA NDC directory, including Genzyme Corporation.

Has Lumizyme been recalled?

The FDA enforcement database lists 1 recall for Lumizyme, most recently D-0799-2016 (class iii): Labeling: Incorrect or Missing Lot and/or Exp Date