Lumizyme (Alglucosidase Alfa)
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Lumizyme (Alglucosidase Alfa)

LUMIZYME
(alglucosidase alfa) for Injection, for Intravenous Use

WARNING

Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during LUMIZYME (alglucosidase alfa) ™ infusions. Therefore, appropriate medical support should be readily available when LUMIZYME is administered [see WARNINGS AND PRECAUTIONS].

Because of the potential risk of rapid disease progression in Pompe disease patients less than 8 years of age, LUMIZYME (alglucosidase alfa) is available only through a restricted distribution program called the LUMIZYME (alglucosidase alfa) ACE ProgramSM. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense or administer LUMIZYME (alglucosidase alfa) . LUMIZYME (alglucosidase alfa) may be administered only to patients who are enrolled in and meet all the conditions of the LUMIZYME (alglucosidase alfa) ACE Program. To enroll in the LUMIZYME (alglucosidase alfa) ACE Program call 1-800-745-4447 [see WARNINGS AND PRECAUTIONS].

DRUG DESCRIPTION

LUMIZYME (alglucosidase alfa) consists of the human enzyme acid α-glucosidase (GAA), encoded by the most predominant of nine observed haplotypes of this gene. LUMIZYME (alglucosidase alfa) is produced by recombinant DNA technology in a Chinese hamster ovary cell line. The LUMIZYME (alglucosidase alfa) manufacturing process differs from that for MYOZYME, resulting in differences in some product attributes. 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 to 5 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). LUMIZYME (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, 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. LUMIZYME (alglucosidase alfa) does not contain preservatives; each vial is for single use only.

What are the possible side effects of alglucosidase alfa (Lumizyme, Myozyme)?

Some people receiving an injection of alglucosidase alfa have had a reaction to the infusion. This type of reaction can occur when the medicine is injected into the vein, or as long as 3 hours after the injection. Tell your caregivers or get emergency medical help right away if you have any of these signs of a severe allergic reaction:

  • feeling like you might pass out, even while lying down;
  • feeling restless, nervous, dizzy, or nauseated;
  • pale skin, redness under your skin, sweating, feeling hot or cold;
  • fast or slow heart...

Read All Potential Side Effects and See Pictures of Lumizyme »

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

LUMIZYME (alglucosidase alfa) [see DESCRIPTION] is a lysosomal glycogen-specific enzyme indicated for patients 8 years and older with late (non-infantile) onset Pompe disease (acid α-glucosidase (GAA) deficiency) who do not have evidence of cardiac hypertrophy. The safety and efficacy of LUMIZYME (alglucosidase alfa) have not been evaluated in controlled clinical trials in infantile-onset patients, or in late (non-infantile) onset patients less than 8 years of age [see Use In Specific Populations].

DOSAGE AND ADMINISTRATION

Recommended Dose

The recommended dosage of LUMIZYME (alglucosidase alfa) is 20 mg/kg body weight administered every 2 weeks as an intravenous infusion.

Instructions for Use

LUMIZYME (alglucosidase alfa) does not contain any preservatives. Vials are single-use only. Discard any unused product.

The total volume of infusion is determined by the patient's body weight and should be administered over approximately 4 hours. 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 (alglucosidase alfa) 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 infusion reactions. See Table 1 below for the rate of infusion at each step, expressed as mL/hr based on the recommended infusion volume by patient weight.

Table 1: Recommended Infusion Volumes and Rates

Patient Weight
Range (kg)
Total infusion volume
(mL)
Step 1
1 mg/kg/hr
(mL/hr)
Step 2
3 mg/kg/hr
(mL/hr)
Step 3
5 mg/kg/hr
(mL/hr)
Step 4
7 mg/kg/hr
(mL/hr)
20.1 – 30 150 8 23 38 53
30.1 – 35 200 10 30 50 70
35.1 – 50 250 13 38 63 88
50.1 – 60 300 15 45 75 105
60.1 – 100 500 25 75 125 175
100.1 – 120 600 30 90 150 210
120.1 – 140 700 35 105 175 245
140.1 – 160 800 40 120 200 280
160.1 – 180 900 45 135 225 315
180.1 – 200 1,000 50 150 250 350

Reconstitution, Dilution, and Administration

LUMIZYME (alglucosidase alfa) should be reconstituted, diluted and administered by a healthcare professional.

Use aseptic technique during preparation. Do not use filter needles during preparation.

  1. Determine the number of vials to be reconstituted based on the individual patient's weight and the recommended dose of 20 mg/kg.
    Patient weight (kg) x dose (mg/kg) = patient dose (in mg)
    Patient dose (in mg) divided by 50 mg/vial = number of vials to reconstitute. If the number of vials includes a fraction, round up to the next whole number.
    Example: Patient weight (68 kg) x dose (20 mg/kg) = patient dose (1,360 mg)
    1,360 mg divided by 50 mg/vial = 27.2 vials; therefore, 28 vials should be reconstituted
    Remove the required number of vials from the refrigerator and allow them to reach room temperature prior to reconstitution (approximately 30 minutes).
  2. Reconstitute each LUMIZYME (alglucosidase alfa) vial by slowly injecting 10.3 mL of Sterile Water for Injection, USP to the inside wall of each vial. Each vial will yield a concentration of 5 mg/mL. The total extractable dose per vial is 50 mg per 10 mL. Avoid forceful impact of the water for injection on the powder and avoid foaming. This is done by slow drop-wise addition of the water for injection down the inside of the vial and not directly onto the lyophilized cake. Tilt and roll each vial gently. Do not invert, swirl, or shake.
  3. The reconstituted LUMIZYME (alglucosidase alfa) solution should be protected from light.
  4. Perform an immediate visual inspection on the reconstituted vials for particulate matter and discoloration. If upon immediate inspection opaque particles are observed or if the solution is discolored do not use. The reconstituted solution may occasionally contain some alglucosidase alfa 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 alglucosidase alfa 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.
  5. LUMIZYME (alglucosidase alfa) should be diluted in 0.9% Sodium Chloride for Injection, USP, immediately after reconstitution, to a final LUMIZYME (alglucosidase alfa) concentration of 0.5 to 4 mg/mL. See Table 1 for the recommended total infusion volume based on patient weight.
  6. Slowly withdraw the reconstituted solution from each vial. Avoid foaming in the syringe.
  7. Remove airspace from the infusion bag to minimize particle formation due to the sensitivity of LUMIZYME (alglucosidase alfa) to air-liquid interfaces.
  8. Add the reconstituted LUMIZYME (alglucosidase alfa) solution slowly and directly into the sodium chloride solution. Do not add directly into airspace that may remain within the infusion bag. Avoid foaming in the infusion bag.
  9. Gently invert or massage the infusion bag to mix. Do not shake.
  10. Administer LUMIZYME (alglucosidase alfa) using an in-line low protein binding 0.2 μm filter.
  11. Do not infuse LUMIZYME (alglucosidase alfa) in the same intravenous line with other products.

LUMIZYME (alglucosidase alfa) does not contain any preservatives. Vials are single-use only. Discard any unused product.

HOW SUPPLIED

Dosage Forms And Strengths

LUMIZYME (alglucosidase alfa) is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder for reconstitution with Sterile Water for Injection, USP to yield a concentration of 5 mg/mL; and then further diluted with 0.9% Sodium Chloride for Injection, USP for intravenous infusion.

Single use vials are available in 50 mg dosage only.

Storage And Handling

LUMIZYME (alglucosidase alfa) 50 mg vials are supplied as a sterile, nonpyrogenic, white to off-white lyophilized cake or powder. LUMIZYME (alglucosidase alfa) is supplied in single-use, clear Type I glass 20 mL (cc) vials. The closure consists of a siliconized butyl stopper and an aluminum seal with a plastic flip-off cap.

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

The reconstituted and diluted solution should be administered without delay. If immediate use is not possible, the reconstituted and diluted solution is stable for up to 24 hours at 2° to 8°C (36° to 46°F). Storage of the reconstituted solution at room temperature is not recommended. The reconstituted and diluted LUMIZYME (alglucosidase alfa) solution should be protected from light. Do not freeze or shake.

LUMIZYME (alglucosidase alfa) does not contain any preservatives. Vials are single-use only. Discard any unused product

NDC 58468-0160-1

LUMIZYME (alglucosidase alfa) is manufactured and distributed by: Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142. 1-800-745-4447 (phone). Revised: 05/2010

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under controlled conditions, the observed adverse reaction rates may not predict the rates observed in patients in clinical practice. Assessment of adverse reactions is based on the exposure of 90 patients (45 male, 45 female) with late-onset Pompe disease, ages 10 to 70 years, to 20 mg/kg LUMIZYME (alglucosidase alfa) or placebo in a randomized, double-blind, placebo-controlled study designed to enroll patients age 8-70 years. The youngest LUMIZYME (alglucosidase alfa) -treated patient was 16 years of age, and the youngest placebo-treated patient was 10 years of age. All patients were naïve to enzyme replacement therapy. Patients were randomized in a 2:1 ratio and received LUMIZYME (alglucosidase alfa) or placebo every other week for 78 weeks (18 months). The study population included 34 males and 26 females (N=60) in the LUMIZYME (alglucosidase alfa) group and 11 males and 19 females (N=30) in the placebo group. Two patients receiving LUMIZYME (alglucosidase alfa) discontinued the study due to anaphylactic reactions. A third patient in the LUMIZYME (alglucosidase alfa) group died during the study due to brain stem ischemia secondary to thrombosis of a basilar aneurysm, which was considered unrelated to treatment.

Serious adverse reactions reported with LUMIZYME (alglucosidase alfa) in the randomized, double-blind, placebo-controlled study included anaphylaxis [see BOXED WARNING and WARNINGS AND PRECAUTIONS]. Anaphylactic reactions included: 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. Other serious adverse events that occurred in a higher incidence in LUMIZYME (alglucosidase alfa) treated patients compared to placebo included coronary artery disease, intervertebral disc protrusion, pneumonia, gastroenteritis, and dehydration.

The most common adverse reactions observed were infusion reactions. Infusion reactions, defined as an adverse reaction occurring during the infusion or within 2 hours after completion of the infusion, that occurred in LUMIZYME (alglucosidase alfa) treated patients at an incidence of ≥ 5% compared to placebo in the controlled study included anaphylaxis, urticaria, diarrhea, vomiting, dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis, flushing/feeling hot, pain in extremity, fall and chest discomfort. Additional infusion reactions observed in other clinical trials and expanded access programs with LUMIZYME (alglucosidase alfa) included respiratory distress, cough, livedo reticularis, agitation, irritability, retching, rigors, tremor and increased lacrimation.

If an infusion reaction occurs, decreasing the infusion rate, temporarily stopping the infusion, and/or administration of antihistamines and/or antipyretics may ameliorate the symptoms. If severe infusion or allergic reactions occur, immediate discontinuation of the administration of LUMIZYME (alglucosidase alfa) should be considered, and appropriate medical treatment should be initiated [see WARNINGS AND PRECAUTIONS]. Severe infusion reactions are generally managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylactic reactions, epinephrine was administered. Patients who have experienced infusion reactions should be treated with caution when they are re-administered LUMIZYME (alglucosidase alfa) .

Delayed onset infusion reactions have also been observed with LUMIZYME (alglucosidase alfa) infusion. Delayed onset infusion reactions, defined as adverse reactions that occurred within 48 hours after completion of LUMIZYME (alglucosidase alfa) infusion, occurred in LUMIZYME (alglucosidase alfa) treated patients at an incidence of ≥ 3% compared to placebo treated patients in a controlled trial. Symptoms included urticaria, dizziness, procedural pain, pharyngolaryngeal pain, malaise, muscle spasms, musculoskeletal pain, musculoskeletal weakness, musculoskeletal stiffness, neck pain, insomnia, and epistaxis. Patients should be counseled about the possibility of delayed onset infusion reactions and given proper follow up instructions.

Table 2 enumerates adverse reactions that occurred in LUMIZYME (alglucosidase alfa) treated patients at an incidence of ≥ 5% compared to placebo treated patients during the randomized, double-blind, placebo-controlled study. Reported adverse reactions have been classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology System Organ Class and Preferred Term.

Table 2: Summary of Adverse Reactions Occurring in LUMIZYME (alglucosidase alfa) Treated Patients at an Incidence ≥ 5% Compared to Placebo Treated Patients

System Organ Class Preferred Term LUMIZYME (alglucosidase alfa)
n=60
N(%)
Placebo
n=30
N (%)
Blood and lymphatic system disorders Lymphadenopathy 5 (8.3) 0 (0)
Ear and labyrinth disorders Hypoacusis 20 (33.3) 7 (23.3)
Vertigo 4 (6.7) 0 (0)
Ear discomfort or pain 7 (11.7) 2 (6.7)
Eye disorders Vision blurred 3 (5) 0 (0)
Gastrointestinal disorders Constipation 6 (10) 0 (0)
Dyspepsia 5 (8.3) 0 (0)
Vomiting 13 (21.7) 3 (10)
General disorders and administration site conditions Chest discomfort or pain 10 (16.7) 2 (6.7)
Infusion site reactions 8 (13.3) 0 (0)
Malaise 3 (5) 0 (0)
Edema, peripheral 10 (16.7) 3 (10)
Pain 5 (8.3) 1 (3.3)
Immune system disorders Anaphylaxis 4 (6.7) 0 (0)
Infections and infestations Gastroenteritis 6 (10) 1 (3.3)
Respiratory tract infection 3 (5) 0 (0)
Upper respiratory tract infection 11 (18.3) 3 (10)
Injury, poisoning and procedural complications Procedural pain 9 (15) 3 (10)
Metabolism and nutrition disorders Hypokalemia 3 (5) 0 (0)
Musculoskeletal and connective tissue disorders Muscle twitching 5 (8.3) 1 (3.3)
Musculoskeletal pain 22 (36.7) 9 (30)
Musculoskeletal stiffness or tightness 9 (15) 2 (6.7)
Nervous system disorders Somnolence 3 (5) 0 (0)
Tremor 4 (6.7) 0 (0)
Renal and urinary disorders Nephrolithiasis 3 (5) 0 (0)
Respiratory, thoracic and mediastinal disorders Dyspnea, exertional 4 (6.7) 0 (0)
Epistaxis 3 (5) 0 (0)
Skin and subcutaneous tissue disorders Hyperhidrosis 5 (8.3) 0 (0)
Pruritis 6 (10) 1 (3.3)
Urticaria 6 (10) 0 (0)

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. The data reflect the percentage of patients whose tests results were considered positive for antibodies to alglucosidase alfa using an enzyme-linked immunosorbent assay (ELISA) and confirmed by a radioimmunoprecipitation (RIP) assay for alglucosidase alfa-specific IgG antibodies. The incidence of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including inhibitory antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to alglucosidase alfa with the incidence of antibodies to other products may be misleading.

In the randomized, double-blind, placebo-controlled study, all patients with available samples treated with LUMIZYME (N=59, 100%) developed IgG antibodies to alglucosidase alfa. All patients who developed IgG antibodies did so within the first 3 months of exposure (median time to seroconversion was 4 weeks). There was no apparent association between mean or peak IgG antibody titers and the occurrence of adverse reactions.

Patients who developed IgG antibodies to alglucosidase alfa were also evaluated for inhibition of enzyme activity or cellular uptake of enzyme in in vitro assays. None of the 59 evaluable patients tested positive for inhibition of enzyme activity. Antibody titers for cellular uptake inhibition were present in 18 of 59 patients (31%) by Week 78. All other patients tested negative for inhibition of cellular uptake. Patients who were positive for uptake inhibition tended to have higher IgG titers than patients who tested negative for uptake inhibition. Among the 32 patients with evaluable pharmacokinetic (PK) samples, 5 patients tested positive for uptake inhibition at times corresponding to PK sampling times as compared to other patients. The clearance values for 4 of these 5 patients were approximately 1.2- to 1.8-fold greater in the presence (Week 52) as compared to in the absence of inhibitory antibodies (Week 0) [see CLINICAL PHARMACOLOGY].

Patients in the clinical studies or in the postmarketing setting have undergone testing for alglucosidase alfa-specific IgE antibodies. Testing was performed in patients who experienced moderate to severe or recurrent infusion reactions, for which mast-cell activation was suspected.

Ten patients in the randomized, double-blind, placebo-controlled study underwent testing for alglucosidase alfa-specific IgE antibodies. Two of 10 patients evaluated tested positive for alglucosidase alfa-specific IgE-binding antibodies, both of whom experienced anaphylactic reactions [see BOXED WARNING and WARNINGS AND PRECAUTIONS]. One patient who developed IgE antibodies discontinued the study following anaphylaxis.

A small number of LUMIZYME (alglucosidase alfa) treated patients in the postmarketing setting who were evaluated tested positive for presence of alglucosidase alfa-specific IgE antibodies. Some of these patients experienced anaphylaxis [see BOXED WARNING and WARNINGS AND PRECAUTIONS].

Some patients who tested positive for alglucosidase alfa-specific IgE antibodies were successfully rechallenged with LUMIZYME (alglucosidase alfa) using a slower infusion rate at lower initial doses and have continued to receive treatment under close clinical supervision [see WARNINGS AND PRECAUTIONS].

Patients who develop IgE antibodies to alglucosidase alfa appear to be at a higher risk for the occurrence of anaphylaxis and severe allergic reactions [see WARNINGS AND PRECAUTIONS]. Therefore, these patients should be monitored more closely during administration of LUMIZYME (alglucosidase alfa) .

Postmarketing Experience

The following adverse reactions have been identified during post approval use of LUMIZYME (alglucosidase alfa) . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In postmarketing experience with LUMIZYME (alglucosidase alfa) , deaths, and serious adverse reactions have been reported, including anaphylaxis [see BOXED WARNING and WARNINGS AND PRECAUTIONS]. Adverse events resulting in death reported in the postmarketing setting with LUMIZYME (alglucosidase alfa) treatment included cardiorespiratory arrest, respiratory failure, hemothorax, pneumothorax, cardiac failure, sepsis, aortic dissection, cerebrovascular accident, and skin necrosis. The most frequently reported serious adverse reactions were infusion reactions. In addition to the infusion reactions reported in clinical trials, the following serious adverse events have been reported in at least 2 patients: dyspnea, respiratory failure, bronchospasm, stridor, decreased oxygen saturation/hypoxia, pharyngeal edema, chest discomfort, chest pain, hypotension, hypertension, erythema, flushing, lung infection, tachycardia, cyanosis, and hypersensitivity. One case of hyperparathyroidism has been reported.

Systemic and cutaneous immune mediated reactions, including necrotizing skin lesions have been reported in postmarketing safety experience with alglucosidase alfa [see WARNINGS AND PRECAUTIONS].

Read the Lumizyme (alglucosidase alfa) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Interference with Other Drugs

No drug interaction or in vitro metabolism studies were performed.

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Anaphylaxis and Allergic Reactions

(see BOXED WARNING)

Anaphylaxis and severe allergic reactions have been observed in patients during and up to 3 hours after LUMIZYME (alglucosidase alfa) infusion. Some of the reactions were life-threatening and included anaphylactic shock, respiratory arrest, apnea, dyspnea, bradycardia, tachycardia, and hypotension. Other accompanying reactions included chest discomfort/pain, throat tightness, bronchospasm, wheezing, tachypnea, cyanosis, decreased oxygen saturation/hypoxia, convulsions, angioedema (including tongue or lip swelling, periorbital edema, and face edema), pruritus, rash, urticaria, hyperhidrosis, nausea, dizziness, hypertension, flushing/erythema, fever, pallor, peripheral coldness, feeling hot, restlessness, nervousness, headache, back pain, and paraesthesia. Some of these reactions were IgE-mediated [see ADVERSE REACTIONS].

If anaphylaxis or other severe allergic reactions occur, immediate discontinuation of the administration of LUMIZYME (alglucosidase alfa) should be considered, and appropriate medical treatment should be initiated. Severe reactions are generally managed with infusion interruption, administration of antihistamines, corticosteroids, intravenous fluids, and/or oxygen, when clinically indicated. In some cases of anaphylaxis, epinephrine has been administered. Because of the potential for severe allergic reactions, appropriate medical support, including cardiopulmonary resuscitation equipment, should be readily available when LUMIZYME (alglucosidase alfa) is administered.

The risks and benefits of re-administering LUMIZYME (alglucosidase alfa) following an anaphylactic or severe allergic reaction should be considered. Some patients have been rechallenged and have continued to receive LUMIZYME (alglucosidase alfa) under close clinical supervision. Extreme care should be exercised, with appropriate resuscitation measures available, if the decision is made to re-administer the product [see ADVERSE REACTIONS].

Immune Mediated Reactions

(see BOXED WARNING)

Severe cutaneous reactions have been reported with alglucosidase alfa including necrotizing skin lesions [see ADVERSE REACTIONS ]. Systemic immune mediated reactions, including possible type III immune complex-mediated reactions have been observed with alglucosidase alfa. These reactions occurred several weeks to 3 years after initiation of alglucosidase alfa infusions. Skin biopsy in one patient demonstrated deposition of anti-rhGAA antibodies in the lesion. Another patient developed severe inflammatory arthropathy in association with fever and elevated erythrocyte sedimentation rate. Patients should be monitored for the development of systemic immune complex-mediated reactions involving skin and other organs while receiving LUMIZYME (alglucosidase alfa) . If immune mediated reactions occur, discontinuation of the administration of LUMIZYME (alglucosidase alfa) should be considered, and appropriate medical treatment initiated. The risks and benefits of re-administering alglucosidase alfa following an immune mediated reaction should be considered. Some patients have successfully been rechallenged and have continued to receive alglucosidase alfa under close clinical supervision.

Distribution Program for LUMIZYME

(see BOXED WARNING)

Lumizyme (alglucosidase alfa) is available only under a restricted distribution program called the Lumizyme ACE (Alglucosidase Alfa Control and Education) Program.

The purpose of the program is to ensure that the known risks of anaphylaxis and severe allergic reactions and the potential risks of severe cutaneous and systemic immune complex-mediated reactions associated with the use of LUMIZYME (alglucosidase alfa) are communicated to patients, caregivers, and prescribers. In addition, the purpose of the program is to mitigate the potential risk of rapid disease progression in infantile-onset Pompe disease patients and late (non-infantile) onset Pompe disease patients less than 8 years of age for whom the safety and effectiveness of LUMIZYME (alglucosidase alfa) have not been evaluated.

Under this program, only trained and certified prescribers, and healthcare facilities enrolled in the program are able to prescribe, dispense or administer Lumizyme (alglucosidase alfa) , and only patients who are enrolled in and meet all the conditions of the Lumizyme (alglucosidase alfa) ACE Program may receive Lumizyme (alglucosidase alfa) .

For information about the ACE Program call 1-800-745-4447.

Risk of Acute Cardiorespiratory Failure

Patients with acute underlying respiratory illness or compromised cardiac and/or respiratory function may be at risk of serious exacerbation of their cardiac or respiratory compromise during infusions. Appropriate medical support and monitoring measures should be readily available during LUMIZYME (alglucosidase alfa) infusion, and some patients may require prolonged observation times that should be based on the individual needs of the patient. Acute cardiorespiratory failure has been observed in a few infantile-onset Pompe disease patients with underlying cardiac hypertrophy, possibly associated with fluid overload with intravenous administration of alglucosidase alfa [see DOSAGE AND ADMINISTRATION].

Precautions for General/Regional Anesthesia

Administration of general anesthesia can be complicated by the presence of severe cardiac and skeletal (including respiratory) muscle weakness. Cardiac arrhythmia has been observed in infantile-onset patients with cardiac hypertrophy, associated with the use of general anesthesia. As Pompe disease is considered a neuromuscular disease, caution should be used when administering general anesthesia in Pompe disease patients.

Monitoring: Laboratory Tests

Patients should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter. Testing for IgG titers may also be considered if patients develop allergic or other immune mediated reactions. Patients who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis [see ADVERSE REACTIONS].

There are currently no marketed tests for antibodies against alglucosidase alfa, however a testing service is provided by Genzyme. Contact your local Genzyme representative or Genzyme Corporation at 1-800-745-4447 for information on testing and to obtain a sample collection box.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate carcinogenic potential or studies to evaluate mutagenic potential have not been performed with alglucosidase alfa.

Alglucosidase alfa at intravenous doses up to 40 mg/kg, administered every other day (plasma AUC of 64.6 mg•min/mL, 0.4 times the human exposure at the recommended bi-weekly dose) had no effect on fertility and reproductive performance in mice.

Use In Specific Populations

Pregnancy

Teratogenic Effects - Pregnancy Category B.

Reproduction studies have been performed in pregnant mice at intravenous doses up to 40 mg/kg/day (plasma AUC of 64.6 mg•min/mL, 0.4 times the human steady-state exposure at the recommended bi-weekly dose) and pregnant rabbits at intravenous doses up to 40 mg/kg/day (plasma AUC of 85 mg•min/mL, 0.5 times the human steady-state exposure at the recommended bi-weekly dose) and have revealed no evidence of impaired fertility or harm to the fetus due to alglucosidase alfa. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Women of childbearing potential are encouraged to enroll in the Pompe Registry [see PATIENT INFORMATION].

Labor and Delivery

Information on the effect of LUMIZYME (alglucosidase alfa) on labor and delivery is unknown. Pregnant women are encouraged to enroll in the Pompe Registry [see PATIENT INFORMATION].

Nursing Mothers

It is not known whether LUMIZYME (alglucosidase alfa) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when LUMIZYME (alglucosidase alfa) is administered to a nursing woman. Nursing women are encouraged to enroll in the Pompe Registry [see PATIENT INFORMATION].

Pediatric Use

LUMIZYME (alglucosidase alfa) is not for use in patients with infantile-onset Pompe disease or late (non-infantile) onset Pompe disease who are less than 8 years of age. The safety and effectiveness of LUMIZYME (alglucosidase alfa) in these patients have not been evaluated in clinical trials.

The safety and effectiveness of LUMIZYME (alglucosidase alfa) was assessed in a randomized, double-blind, placebo-controlled study of 90 patients with late (non-infantile) onset Pompe disease. Patients age 8 to 70 years were eligible for enrollment. The study included 2 patients 16 years of age or less (n=1, age 16 years, LUMIZYME (alglucosidase alfa) treatment group, n=1, age 10 years, placebo group) [see Clinical Studies].

Geriatric Use

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

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

There have been no reports of overdose with LUMIZYME (alglucosidase alfa) . In the placebo-controlled study, patients received doses up to 20 mg/kg body weight every other week.

CONTRAINDICATIONS

None.

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

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.

LUMIZYME (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.

Pharmacodynamics

Clinical pharmacodynamic studies have not been conducted for LUMIZYME (alglucosidase alfa) .

Pharmacokinetics

The pharmacokinetics of alglucosidase alfa were studied in 32 late-onset Pompe disease patients from the randomized, double-blind, placebo-controlled study ranging in age from 21 to 70 years old who received LUMIZYME (alglucosidase alfa) 20 mg/kg every other week. The pharmacokinetics were not-time dependent for patients who did not develop high antibody titer/inhibitory antibody. Parameter values did not change across visits at Weeks 0, 12, and 52. At Week 52 of bi-weekly administration the estimates of AUC (2700 mcg·h/mL with 30.4% coefficient of variation [CV],n=29), Cmax (372 mcg /mL with 22.7% CV,n=29) and clearance (601 mL/h with 28.2% CV,n=29) were determined at steady-state. The declining portion of the concentration-time profile of alglucosidase alfa appears biphasic within the observed sampling time. The half-life for the first phase is 2.4 hours with a between subject variation of 10%. Concentrations of alglucosidase alfa were not sampled long enough to adequately determine the half-life for the second phase.

Higher mean clearance (42%) was observed at Week 52 in 4 of 5 patients that tested positive for antibodies that inhibit the cellular uptake of enzyme. Pharmacokinetics in 4 of these 5 individuals over time indicated an increase in clearance with increase in IgG titer. Positive inhibitory antibody status correlated with higher IgG titers in patients who received LUMIZYME (alglucosidase alfa) . The relationship between exposure and efficacy has not been defined.

Clinical Studies

Controlled clinical trials

The safety and efficacy of LUMIZYME (alglucosidase alfa) was assessed in 90 patients with late-onset Pompe disease, ages 10 to 70 years, in a randomized double-blind, placebo-controlled study designed to enroll patients age 8-70 years. The youngest LUMIZYME (alglucosidase alfa) -treated patient was 16 years of age, and the youngest placebo-treated patient was 10 years of age. All patients were naïve to enzyme replacement therapy. Patients were allocated in a 2:1 ratio and received 20 mg/kg LUMIZYME (alglucosidase alfa) (n=60) or placebo (n=30) every other week for 78 weeks (18 months). The study population included 34 males and 26 females (N=60) in the LUMIZYME (alglucosidase alfa) group and 11 males and 19 females (N=30) in the placebo group. At baseline, all patients were ambulatory (some required assistive walking devices), did not require invasive ventilator support or non-invasive ventilation while awake and sitting upright and had a forced vital capacity (FVC) between 30 and 79% of predicted in the sitting position. Patients who could not walk 40 meters in 6 minutes or were unable to perform appropriate pulmonary and muscle function testing were excluded from the study.

A total of 81 of 90 patients completed the study. Of the 9 patients who discontinued, 5 were in the LUMIZYME (alglucosidase alfa) group and 4 were in the placebo group. Three patients discontinued the study due to an adverse event; two patients were in the LUMIZYME (alglucosidase alfa) treatment group and one patient was in placebo group. One patient in the LUMIZYME group died [see ADVERSE REACTIONS]. Four patients discontinued study participation to pursue treatment with commercial therapy, and one patient discontinued the study for personal reasons.

At study entry, the mean % predicted FVC in the sitting position among all patients was about 55%. After 78 weeks, the mean % predicted FVC increased to 56.2% for LUMIZYME (alglucosidase alfa) -treated patients and decreased to 52.8% for placebo-treated patients indicating a LUMIZYME (alglucosidase alfa) treatment effect of 3.4 % (95% confidence interval: [1.3% to 5.5%]; p=0.004). Stabilization of % predicted FVC in the LUMIZYME (alglucosidase alfa) -treated patients was observed (see Figure 1).

Figure 1: Mean FVC Upright (% Predicted) Over Time

Mean FVC Upright (% Predicted) Over Time - Illustration

At study entry, the mean 6 minute walk test (6MWT) among all patients was about 330 meters. After 78 weeks, the mean 6MWT increased by 25 meters for LUMIZYME (alglucosidase alfa) -treated patients and decreased by 3 meters for placebo-treated patients indicating a LUMIZYME (alglucosidase alfa) treatment effect of 28 meters (95% confidence interval: [-1 to 52 meters]; p=0.06) (see Figure 2).

Figure 2: Mean Six Minute Walk Test Total Distance Walked Over Time

Mean Six Minute Walk Test Total Distance Walked Over Time - Illustration

Uncontrolled Studies

The effectiveness of Lumizyme (alglucosidase alfa) has not been established in infantile-onset patients. Descriptive data from infantile-onset patients who have received Lumizyme (alglucosidase alfa) commercially outside the U.S. have been collected in the Pompe Registry. The Pompe Registry is a multi-center, multi-national, voluntary, observational disease registry. Fifteen infantile-onset patients enrolled in the registry were matched to the baseline characteristics of an untreated historical control cohort. These patients were diagnosed with Pompe disease and received treatment with LUMIZYME (alglucosidase alfa) prior to 6 months of age (range 0.6 to 6 months). The median duration of treatment was 15 months (range 3 to 48 months). Estimated survival in LUMIZYME (alglucosidase alfa) -treated patients was 57% at 18 months and 37% at 36 months, compared to the 2% survival in the historical control group at both time points. The median age of death or last follow-up was 19 months (range 5 to 51 months).

Descriptive clinical data from patients with infantile-onset Pompe disease in the Pompe Registry were used to verify the overall effectiveness of LUMIZYME (alglucosidase alfa) for patients 8 years and older with late-onset Pompe disease.

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Distribution Program for LUMIZYME (alglucosidase alfa)

Patients and caregivers should be informed that Lumizyme (alglucosidase alfa) is available only under a restricted distribution program called the LUMIZYME (alglucosidase alfa) ACE (Alglucosidase Alfa Control and Education) Program.

The purpose of the program is to ensure that the known risks of anaphylaxis and severe allergic reactions and the potential risks of severe cutaneous and systemic immune complex-mediated reactions associated with the use of LUMIZYME (alglucosidase alfa) are communicated to patients, caregivers, and prescribers. In addition, the purpose of the program is to mitigate the potential risk of rapid disease progression in infantile-onset Pompe disease patients and late (non-infantile) onset Pompe disease patients less than 8 years of age with for whom the safety and effectiveness of LUMIZYME (alglucosidase alfa) have not been evaluated.

Patients and caregivers should also be informed that only trained and certified prescribers, and healthcare facilities enrolled in the program are able to prescribe, dispense or administer LUMIZYME (alglucosidase alfa) , and that patients must be enrolled in and meet all the conditions of the Lumizyme (alglucosidase alfa) ACE Program to receive Lumizyme (alglucosidase alfa) .

Pompe Registry

Patients and their caregivers should be informed that a registry for patients with Pompe disease (the Pompe Registry) has been established in order to better understand the variability and progression of Pompe disease, and to continue to monitor and evaluate long-term treatment effects of LUMIZYME (alglucosidase alfa) . The Pompe Registry will also monitor the effect of LUMIZYME (alglucosidase alfa) on pregnant women and their offspring [see Use In Specific Populations]. Patients and their caregivers are encouraged to participate in the Pompe Registry and advised that their participation is voluntary and may involve long-term follow-up. For more information regarding the registry program visit www.pomperegistry.com or by calling 1-800-745-4447.

Infusion Reactions

Patients and caregivers should be informed that the most common adverse reactions observed with LUMIZYME (alglucosidase alfa) were infusion reactions. Infusion reactions may occur during or within 2 hours after completion of the infusion. Symptoms associated with infusion reactions include urticaria, diarrhea, vomiting, dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis, flushing/feeling hot, pain in extremity, fall and chest discomfort, respiratory distress, cough, livedo reticularis, agitation, irritability, retching, rigors, tremor and increased lacrimation.

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Distribution Program for LUMIZYME (alglucosidase alfa)

Patients and caregivers should be informed that Lumizyme (alglucosidase alfa) is available only under a restricted distribution program called the LUMIZYME (alglucosidase alfa) ACE (Alglucosidase Alfa Control and Education) Program.

The purpose of the program is to ensure that the known risks of anaphylaxis and severe allergic reactions and the potential risks of severe cutaneous and systemic immune complex-mediated reactions associated with the use of LUMIZYME (alglucosidase alfa) are communicated to patients, caregivers, and prescribers. In addition, the purpose of the program is to mitigate the potential risk of rapid disease progression in infantile-onset Pompe disease patients and late (non-infantile) onset Pompe disease patients less than 8 years of age with for whom the safety and effectiveness of LUMIZYME (alglucosidase alfa) have not been evaluated.

Patients and caregivers should also be informed that only trained and certified prescribers, and healthcare facilities enrolled in the program are able to prescribe, dispense or administer LUMIZYME (alglucosidase alfa) , and that patients must be enrolled in and meet all the conditions of the Lumizyme (alglucosidase alfa) ACE Program to receive Lumizyme (alglucosidase alfa) .

Pompe Registry

Patients and their caregivers should be informed that a registry for patients with Pompe disease (the Pompe Registry) has been established in order to better understand the variability and progression of Pompe disease, and to continue to monitor and evaluate long-term treatment effects of LUMIZYME (alglucosidase alfa) . The Pompe Registry will also monitor the effect of LUMIZYME (alglucosidase alfa) on pregnant women and their offspring [see Use In Specific Populations]. Patients and their caregivers are encouraged to participate in the Pompe Registry and advised that their participation is voluntary and may involve long-term follow-up. For more information regarding the registry program visit www.pomperegistry.com or by calling 1-800-745-4447.

Infusion Reactions

Patients and caregivers should be informed that the most common adverse reactions observed with LUMIZYME (alglucosidase alfa) were infusion reactions. Infusion reactions may occur during or within 2 hours after completion of the infusion. Symptoms associated with infusion reactions include urticaria, diarrhea, vomiting, dyspnea, pruritus, rash/erythema, pharyngolaryngeal pain, neck pain, hypoacusis, flushing/feeling hot, pain in extremity, fall and chest discomfort, respiratory distress, cough, livedo reticularis, agitation, irritability, retching, rigors, tremor and increased lacrimation.

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

LUMIZYME
(alglucosidase alfa) for Injection, for Intravenous Use

WARNING

Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during LUMIZYME (alglucosidase alfa) ™ infusions. Therefore, appropriate medical support should be readily available when LUMIZYME is administered [see WARNINGS AND PRECAUTIONS].

Because of the potential risk of rapid disease progression in Pompe disease patients less than 8 years of age, LUMIZYME (alglucosidase alfa) is available only through a restricted distribution program called the LUMIZYME (alglucosidase alfa) ACE ProgramSM. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense or administer LUMIZYME (alglucosidase alfa) . LUMIZYME (alglucosidase alfa) may be administered only to patients who are enrolled in and meet all the conditions of the LUMIZYME (alglucosidase alfa) ACE Program. To enroll in the LUMIZYME (alglucosidase alfa) ACE Program call 1-800-745-4447 [see WARNINGS AND PRECAUTIONS].

DRUG DESCRIPTION

LUMIZYME (alglucosidase alfa) consists of the human enzyme acid α-glucosidase (GAA), encoded by the most predominant of nine observed haplotypes of this gene. LUMIZYME (alglucosidase alfa) is produced by recombinant DNA technology in a Chinese hamster ovary cell line. The LUMIZYME (alglucosidase alfa) manufacturing process differs from that for MYOZYME, resulting in differences in some product attributes. 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 to 5 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). LUMIZYME (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, 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. LUMIZYME (alglucosidase alfa) does not contain preservatives; each vial is for single use only.

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

LUMIZYME
(alglucosidase alfa) for Injection, for Intravenous Use

WARNING

Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during LUMIZYME (alglucosidase alfa) ™ infusions. Therefore, appropriate medical support should be readily available when LUMIZYME is administered [see WARNINGS AND PRECAUTIONS].

Because of the potential risk of rapid disease progression in Pompe disease patients less than 8 years of age, LUMIZYME (alglucosidase alfa) is available only through a restricted distribution program called the LUMIZYME (alglucosidase alfa) ACE ProgramSM. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense or administer LUMIZYME (alglucosidase alfa) . LUMIZYME (alglucosidase alfa) may be administered only to patients who are enrolled in and meet all the conditions of the LUMIZYME (alglucosidase alfa) ACE Program. To enroll in the LUMIZYME (alglucosidase alfa) ACE Program call 1-800-745-4447 [see WARNINGS AND PRECAUTIONS].

DRUG DESCRIPTION

LUMIZYME (alglucosidase alfa) consists of the human enzyme acid α-glucosidase (GAA), encoded by the most predominant of nine observed haplotypes of this gene. LUMIZYME (alglucosidase alfa) is produced by recombinant DNA technology in a Chinese hamster ovary cell line. The LUMIZYME (alglucosidase alfa) manufacturing process differs from that for MYOZYME, resulting in differences in some product attributes. 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 to 5 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). LUMIZYME (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, 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. LUMIZYME (alglucosidase alfa) does not contain preservatives; each vial is for single use only.

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

LUMIZYME
(alglucosidase alfa) for Injection, for Intravenous Use

WARNING

Life-threatening anaphylactic reactions, severe allergic reactions and immune mediated reactions have been observed in some patients during LUMIZYME (alglucosidase alfa) ™ infusions. Therefore, appropriate medical support should be readily available when LUMIZYME is administered [see WARNINGS AND PRECAUTIONS].

Because of the potential risk of rapid disease progression in Pompe disease patients less than 8 years of age, LUMIZYME (alglucosidase alfa) is available only through a restricted distribution program called the LUMIZYME (alglucosidase alfa) ACE ProgramSM. Only prescribers and healthcare facilities enrolled in the program may prescribe, dispense or administer LUMIZYME (alglucosidase alfa) . LUMIZYME (alglucosidase alfa) may be administered only to patients who are enrolled in and meet all the conditions of the LUMIZYME (alglucosidase alfa) ACE Program. To enroll in the LUMIZYME (alglucosidase alfa) ACE Program call 1-800-745-4447 [see WARNINGS AND PRECAUTIONS].

DRUG DESCRIPTION

LUMIZYME (alglucosidase alfa) consists of the human enzyme acid α-glucosidase (GAA), encoded by the most predominant of nine observed haplotypes of this gene. LUMIZYME (alglucosidase alfa) is produced by recombinant DNA technology in a Chinese hamster ovary cell line. The LUMIZYME (alglucosidase alfa) manufacturing process differs from that for MYOZYME, resulting in differences in some product attributes. 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 to 5 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). LUMIZYME (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, 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. LUMIZYME (alglucosidase alfa) does not contain preservatives; each vial is for single use only.

Last reviewed on RxList: 6/18/2010
This monograph has been modified to include the generic and brand name in many instances.

Lumizyme Patient Information Including Side Effects

Brand Names: Lumizyme, Myozyme

Generic Name: alglucosidase alfa (injection) (Pronunciation: AL gloo KOE si dase AL fa)

What is alglucosidase alfa (Lumizyme)?

Alglucosidase alfa contains an enzyme that naturally occurs in the body in healthy people. Some people lack this enzyme because of a genetic disorder. Alglucosidase alfa helps replace this missing enzyme in such people.

Alglucosidase alfa is used to treat a glycogen storage disorder called Pompe disease, (also called GAA deficiency) in adults and children who are at least 8 years old.

Alglucosidase alfa may also be used for purposes not listed in this medication guide.

What are the possible side effects of alglucosidase alfa (Lumizyme)?

Some people receiving an injection of alglucosidase alfa have had a reaction to the infusion. This type of reaction can occur when the medicine is injected into the vein, or as long as 3 hours after the injection. Tell your caregivers or get emergency medical help right away if you have any of these signs of a severe allergic reaction:

  • feeling like you might pass out, even while lying down;
  • feeling restless, nervous, dizzy, or nauseated;
  • pale skin, redness under your skin, sweating, feeling hot or cold;
  • fast or slow heart rate;
  • pain or tightness in your chest or throat;
  • wheezing, trouble breathing;
  • cold hands, blue lips;
  • back pain;
  • numbness, warmth, redness, or tingly feeling;
  • seizure (convulsions);
  • hives, severe skin rash; or
  • swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • pain or fullness in your ear, problems with hearing;
  • skin ulcers;
  • fast, slow, or uneven heartbeats;
  • weak pulse, fainting, slow breathing (breathing may stop); or
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, sweating, general ill feeling.

Less serious side effects may include:

  • mild skin rash or itching;
  • diarrhea, constipation, upset stomach, vomiting;
  • sore throat, neck pain;
  • pain or swelling in your arms or legs; or
  • pain, swelling, burning, or irritation around the IV needle.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Lumizyme (alglucosidase alfa) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about alglucosidase alfa (Lumizyme)?

Alglucosidase alfa is available only under a special program called ACE. Under this program, only registered doctors and pharmacists can prescribe and dispense alglucosidase alfa. You must be registered in the program and sign documents stating that you understand the risks of using this medication and the possibility of severe allergic reaction. Ask your doctor or call the drug maker if you have questions about the program or the written requirements.

Before receiving this medication, tell your doctor if you have heart disease, lung disease or a breathing disorder, or if you are allergic to mice, hamsters, or drug products made with "murine" proteins.

Before each injection, tell your doctor if you have recently been sick with a cold, flu, or other illness.

Some people receiving an injection of alglucosidase alfa have had a reaction to the infusion. This type of reaction can occur when the medicine is injected into the vein, or as long as 3 hours after the injection.

Tell your caregivers or get emergency medical help right away if you have any signs of a severe allergic reaction, such as feeling restless, nervous, dizzy, numb, tingly, hot or cold, sweaty, nauseated, or lightheaded, or if you have trouble breathing, chest pain or tightness, fast or slow heart rate, hives, severe skin rash, seizure (convulsions), or swelling of your face, lips, tongue, or throat.

Side Effects Centers

Lumizyme Patient Information including How Should I Take

What should I discuss with my health care provider before receiving alglucosidase alfa (Lumizyme)?

You should not receive alglucosidase alfa if you are allergic to it.

If you have any of these other conditions, you may need a dose adjustment or special tests:

  • heart disease;
  • lung disease or breathing disorder;
  • if you are allergic to mice, hamsters, or drug products made with "murine" proteins.

FDA pregnancy category B. Alglucosidase alfa is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether alglucosidase alfa passes into breast milk or if it could harm a nursing baby. Do not receive this medication without telling your doctor if you are breast-feeding a baby.

Your name may be listed on the Pompe Registry. This is to track the progress of your disease and the outcome of your treatment with alglucosidase alfa.

How is alglucosidase alfa given (Lumizyme)?

Alglucosidase alfa is injected into a vein through an IV using an infusion pump. You will receive this injection in a clinic or hospital setting. Alglucosidase alfa must be given slowly, and the IV infusion can take up to 4 hours to complete.

This medication is usually given once every 2 weeks.

Before each injection, tell your doctor if you have recently been sick with a cold, flu, or other illness.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested every 3 months for 2 years and then once every year after that. Visit your doctor regularly.

Alglucosidase alfa is available only under a special program called ACE. Under this program, only registered doctors and pharmacists can prescribe and dispense alglucosidase alfa. You must be registered in the program and sign documents stating that you understand the risks of using this medication and the possibility of severe allergic reaction. Ask your doctor or call the drug maker if you have questions about the program or the written requirements.

Side Effects Centers

Lumizyme Patient Information including If I Miss a Dose

What happens if I miss a dose (Lumizyme)?

Call your doctor for instructions if you miss an appointment for your alglucosidase alfa injection.

What happens if I overdose (Lumizyme)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while receiving alglucosidase alfa (Lumizyme)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

What other drugs will affect alglucosidase alfa (Lumizyme)?

There may be other drugs that can interact with alglucosidase alfa. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about alglucosidase alfa.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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Side Effects Centers

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