Alglucosidase Alfa

FDA Drug Information • Also known as: Lumizyme

Brand Names: Lumizyme
Dosage Form: SOLUTION
Product Type: DRUG FOR FURTHER PROCESSING

⚠ Boxed Warning (Black Box)

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 proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following LUMIZYME treatment. Monitor patients for the development of systemic immune-mediated reactions involving skin and other organs while receiving LUMIZYME. ( 5.3 ) Risk of Acute Cardiorespiratory Failure Infantile-onset Pompe disease (IOPD) patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to fluid overload and require additional monitoring. ( 5.4 ) Hypersensitivity Reactions Including Anaphylaxis Patients treated with enzyme replacement therapies have experienced life-threatening 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. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1) ]. Immune-Mediated Reactions Immune-mediated reactions presenting as proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following LUMIZYME treatment. Monitor patients for the development of systemic immune-mediated reactions involving skin and other organs while receiving LUMIZYME [see Warnings and Precautions (5.3) ] . Risk of Acute Cardiorespiratory Failure Infantile-onset Pompe disease (IOPD) patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to fluid overload and require additional monitoring [see Warnings and Precautions (5.4) ] .

Description

11 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.

What Is Alglucosidase Alfa Used For?

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

2 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS 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,...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

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...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING LUMIZYME 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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.