Myozyme

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Myozyme

Classes

Pompe Disease Agents

Administration

For storage information, see the specific product information within the How Supplied Section.
 
NOTE: If patients develop an infusion reaction, the infusion rate should be decreased or stopped temporarily; administration of antihistamines and/or antipyretics may alleviate some of the symptoms. If severe infusion reactions occur, including hypersensitivity reactions or anaphylaxis, discontinue the infusion immediately; appropriate supportive measures should be instituted.
 
NOTE: Patients can be pretreated with antihistamines, antipyretics, and/or corticosteroids approximately 30 minutes prior to each infusion; however, data on the effectiveness of pretreatment in the prevention of infusion-related reactions are conflicting.

Injectable Administration Intravenous Administration

Reconstitution
Do not use filter needles during preparation.
Calculate the required dose and number of vials to be diluted by multiplying the patient's weight by 20 mg/kg and dividing by 50. Round up to the nearest whole vial.
Remove the required number of vials from the refrigerator and allow them to reach room temperature (approximately 30 minutes).
Using aseptic technique, slowly, in a drop-wise manner, inject 10.3 mL of Sterile Water for Injection to the inside wall of each vial; avoid foaming. Do not inject the Sterile Water for Injection directly onto the lyophilized cake. Tilt and roll each vial gently. Do not invert, swirl, or shake. Once reconstituted, each vial contains 50 mg of alglucosidase alfa at a final concentration of 5 mg/mL. Discard any unused product.
Immediately inspect the reconstituted vials for particulate matter and discoloration. Do not use if opaque particles or discoloration are present. However, following reconstitution, alglucosidase alfa particles, which appear as thin white strands or translucent fibers are possible (usually less than 10/vial). These particles are removed via in-line filtration during infusion and do not have a detectable effect on the purity or strength.
Storage: If immediate use is not possible, the reconstituted solution is stable for up to 24 hours refrigerated at 2 to 8 degrees C (36 to 46 degrees F). Storage at room temperature is not recommended. Protect from light. Do not freeze.
 
Dilution
Dilute the solution in 0.9% Sodium Chloride Injection immediately after reconstitution to a final alglucosidase alfa concentration of 0.5 to 4 mg/mL.
Prior to injecting the reconstituted alglucosidase alfa into the 0.9% Sodium Chloride Injection, remove airspace from the infusion bag to minimize particle formation. Alglucosidase alfa is sensitive to air-liquid interfaces.
Slowly withdraw the reconstituted solution from each vial. Avoid foaming in the syringe. Inject the reconstituted alglucosidase alfa slowly and directly into the 0.9% Sodium Chloride Injection. Do not add directly into airspace that may remain within the infusion bag. Avoid foaming in the infusion bag. Gently invert or massage the infusion bag to mix. Do not shake.
Storage: Administer without delay. If immediate use is not possible, the diluted solution is stable for up to 24 hours refrigerated at 2 to 8 degrees C (36 to 46 degrees F). Protect from light. Do not freeze.
 
Intravenous infusion
Administer via intravenous (IV) infusion only.
The diluted IV infusion solution should be filtered through a 0.2 micrometer, low protein-binding, in-line filter during administration so that visible particles are removed.
Do not infuse in the same intravenous line with other products.
Administer the diluted IV infusion solution over 4 hours.
The initial infusion rate of 1 mg/kg/hour may be increased by 2 mg/kg/hour every 30 minutes, as tolerated. Measure vital signs at the end of each step. If vital signs are stable, the rate can be titrated to a maximum of 7 mg/kg/hour. The maximum rate is then maintained for the duration of the infusion.
For patients weighing 1.25 to 2.5 kg: The total infusion volume = 25 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 1.25 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 3.75 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 6.25 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 6.6 mL/hour.
For patients weighing 2.6 to 10 kg: The total infusion volume = 50 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 3 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 8 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 13 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 18 mL/hour.
For patients weighing 10.1 to 20 kg: The total infusion volume = 100 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 5 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 15 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 25 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 35 mL/hour.
For patients weighing 20.1 to 30 kg: The total infusion volume = 150 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 8 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 23 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 38 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 53 mL/hour.
For patients weighing 30.1 to 35 kg: The total infusion volume = 200 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 10 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 30 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 50 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 70 mL/hour.
For patients weighing 35.1 to 50 kg: The total infusion volume = 250 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 13 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 38 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 63 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 88 mL/hour.
For patients weighing 50.1 to 60 kg: The total infusion volume = 300 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 15 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 45 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 75 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 105 mL/hour.
For patients weighing 60.1 to 100 kg: The total infusion volume = 500 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 25 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 75 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 125 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 175 mL/hour.
For patients weighing 100.1 to 120 kg: The total infusion volume = 600 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 30 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 90 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 150 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 210 mL/hour.
For patients weighing 120.1 to 140 kg: The total infusion volume = 700 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 35 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 105 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 175 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 245 mL/hour.
For patients weighing 140.1 to 160 kg: The total infusion volume = 800 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 40 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 120 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 200 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 280 mL/hour.
For patients weighing 160.1 to 180 kg: The total infusion volume = 900 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 45 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 135 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 225 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 315 mL/hour.
For patients weighing 180.1 to 200 kg: The total infusion volume = 1,000 mL. To achieve a dose of 1 mg/kg/hour, the infusion rate is 50 mL/hour; for a dose of 3 mg/kg/hour, the infusion rate is 150 mL/hour; for a dose of 5 mg/kg/hour, the infusion rate is 250 mL/hour; and for a dose of 7 mg/kg/hour, the infusion rate is 350 mL/hour.

Adverse Reactions
Severe

bradycardia / Rapid / 21.0-21.0
anaphylactic shock / Rapid / 1.0-7.0
cardiac arrest / Early / 1.0-1.0
angioedema / Rapid / Incidence not known
apnea / Delayed / Incidence not known
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
ventricular tachycardia / Early / Incidence not known
ventricular fibrillation / Early / Incidence not known
heart failure / Delayed / Incidence not known
respiratory arrest / Rapid / Incidence not known
glomerulonephritis / Delayed / Incidence not known
nephrotic syndrome / Delayed / Incidence not known
skin necrosis / Early / Incidence not known

Moderate

antibody formation / Delayed / 89.0-99.0
anemia / Delayed / 31.0-31.0
candidiasis / Delayed / 31.0-31.0
sinus tachycardia / Rapid / 8.0-23.0
constipation / Delayed / 23.0-23.0
chest pain (unspecified) / Early / 6.0-7.0
peripheral edema / Delayed / 3.0-3.0
edema / Delayed / Incidence not known
dyspnea / Early / Incidence not known
hypotension / Rapid / Incidence not known
hypoxia / Early / Incidence not known
supraventricular tachycardia (SVT) / Early / Incidence not known
proteinuria / Delayed / Incidence not known
skin ulcer / Delayed / Incidence not known

Mild

diarrhea / Early / 0-62.0
diaper dermatitis / Delayed / 36.0-36.0
pharyngitis / Delayed / 9.0-36.0
rhinorrhea / Early / 28.0-28.0
gastroesophageal reflux / Delayed / 26.0-26.0
urticaria / Rapid / 8.0-21.0
abdominal pain / Early / 15.0-15.0
malaise / Early / 6.0-6.0
rhinitis / Early / 6.0-6.0
maculopapular rash / Early / Incidence not known
infection / Delayed / Incidence not known
arthropathy / Delayed / Incidence not known

Boxed Warning
Cardiac disease, cardiomyopathy, heart failure, respiratory insufficiency, sepsis, surgery

Patients with advanced Pompe disease often have underlying compromised cardiac and respiratory function and should be monitored more closely than other patients during use of alglucosidase alfa. Acute cardiorespiratory failure (heart failure and respiratory insufficiency) requiring intubation and inotropic support has been observed up to 3 days after infusion in infantile-onset Pompe disease patients with pre-existing cardiac hypertrophic cardiomyopathy. Any patients with compromised cardiac and/or respiratory function (e.g., cardiac disease, heart failure, respiratory insufficiency, respiratory illness, sepsis) may be at risk for serious acute exacerbation of their cardiac or respiratory status due to fluid overload. These patients require additional monitoring. Appropriate medical support and monitoring should be readily available during each infusion, and some patients may require prolonged observation times that should be based on the individual patient needs. Careful consideration should be given to the patient's clinical status prior to the administration of alglucosidase alfa. In addition, the administration of general anesthesia can be complicated by the presence of severe cardiac disease and skeletal muscle disease, including respiratory muscle weakness. Exercise caution when administering general anesthesia for any reason, including surgery or the placement of a central venous catheter intended for alglucosidase alfa infusion. Ventricular arrhythmias and bradycardia, resulting in cardiac arrest and death, or requiring cardiac resuscitation or defibrillation have been observed in infantile-onset Pompe disease patients with cardiac hypertrophy.

Common Brand Names

Lumizyme

Dea Class

Rx

Description

Enzyme replacement therapy
Used to treat patients with acid alpha-glucosidase deficiency (Pompe disease, glycogen storage disease II)
Myozyme FDA-approved for infantile-onset disease; Lumizyme FDA-approved for infantile- and late-onset disease  

Dosage And Indications
For the treatment of acid alpha-glucosidase deficiency (Pompe disease).
NOTE: Alglucosidase alfa was designated as an orphan drug for the treatment of Pompe disease in 1997.
NOTE: Initiation of alglucosidase alfa therapy in the earliest stages of the disease process is associated with the most clinical benefit.
For the treatment of infantile-onset acid alpha-glucosidase deficiency (Pompe disease). Intravenous dosage Infants and Children

20 mg/kg/dose IV administered over about 4 hours every 2 weeks. The total infusion volume is based on the patient's weight. The initial infusion rate should be no more than 1 mg/kg/hour with titrations of 2 mg/kg/hour every 30 minutes up to a maximum rate of 7 mg/kg/hour; measure vital signs at the end of each titration. Only increase the infusion rate if the patient is stable. If infusion reactions occur, the infusion may be slowed or temporarily stopped; if severe reactions occur, discontinue the infusion. Doses of 40 mg/kg IV once every 2 weeks have also been studied; however, no differences in outcomes between 20 mg/kg and 40 mg/kg IV are apparent.

Neonates

20 mg/kg/dose IV administered over about 4 hours every 2 weeks. The total infusion volume is based on the patient's weight. The initial infusion rate should be no more than 1 mg/kg/hour with titrations of 2 mg/kg/hour every 30 minutes up to a maximum rate of 7 mg/kg/hour; measure vital signs at the end of each titration. Only increase the infusion rate if the patient is stable. If infusion reactions occur, the infusion may be slowed or temporarily stopped; if severe reactions occur, discontinue the infusion. Doses of 40 mg/kg IV once every 2 weeks have also been studied; however, no differences in outcomes between 20 mg/kg and 40 mg/kg IV are apparent.

For the treatment of late-onset (non-infantile) acid alpha-glucosidase deficiency (Pompe disease) . Intravenous dosage (Lumizyme only) Adults

20 mg/kg/dose IV administered over about 4 hours every 2 weeks. The total infusion volume is based on the patient's weight. The initial infusion rate should be no more than 1 mg/kg/hour with titrations of 2 mg/kg/hour every 30 minutes up to a maximum rate of 7 mg/kg/hour; measure vital signs at the end of each titration. Only increase the infusion rate if the patient is stable. If infusion reactions occur, the infusion may be slowed or temporarily stopped; if severe reactions occur, discontinue the infusion.

Children and Adolescents

20 mg/kg/dose IV administered over about 4 hours every 2 weeks. The total infusion volume is based on the patient's weight. The initial infusion rate should be no more than 1 mg/kg/hour with titrations of 2 mg/kg/hour every 30 minutes up to a maximum rate of 7 mg/kg/hour; measure vital signs at the end of each titration. Only increase the infusion rate if the patient is stable. If infusion reactions occur, the infusion may be slowed or temporarily stopped; if severe reactions occur, discontinue the infusion.

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

There are no drug interactions associated with Alglucosidase alfa products.

How Supplied

Lumizyme Intravenous Inj Pwd F/Sol: 52.5mg

Maximum Dosage
Adults

20 mg/kg/dose IV every 2 weeks.

Geriatric

Safety and efficacy have not been established.

Adolescents

20 mg/kg/dose IV every 2 weeks.

Children

20 mg/kg/dose IV every 2 weeks.

Infants

20 mg/kg/dose IV every 2 weeks.

Neonates

20 mg/kg/dose IV every 2 weeks.

Mechanism Of Action

Recombinant human alglucosidase alfa provides exogenous human lysosomal acid alpha-glucosidase; alglucosidase alfa is used primarily in patients with Pompe disease, which is an inherited disorder of glycogen metabolism caused by the relative or absolute absence of acid alpha-glucosidase. Deficiency in acid alpha-glucosidase results in accumulation of lysosomal glycogen both in tissues and intracellularly; the most commonly affected cells are cardiac, skeletal, and smooth muscle. Accumulation of glycogen leads to the development of cardiomyopathy, progressive muscle weakness, and impairment of respiratory function. Treatment with alglucosidase is associated with prolonging life by improving cardiac, respiratory, and skeletal muscle function. In general, alglucosidase alfa will have the most beneficial effects when initiated in those patients without extensive muscle deterioration.
 
Once available systemically, alglucosidase alfa mimics endogenous acid alpha-glucosidase. Alglucosidase alfa binds to the mannose-6-phosphate receptors on cellular surfaces and is internalized and transported into lysosomes. Once in the lysosome, alglucosidase alfa undergoes proteolytic cleavage resulting in increased enzymatic activity and cleavage of glycogen.

Pharmacokinetics

Alglucosidase alfa is administered via intravenous infusion over 4 hours or longer.

Intravenous Route

After intravenous administration, alglucosidase alfa binds to mannose-6-phosphate receptors on cellular surfaces; alglucosidase alfa is internalized and transported to lysozymes, where it undergoes proteolytic cleavage and exerts its therapeutic effects. The pharmacokinetics of alglucosidase alfa were evaluated in 10 adult patients (age range: 19 to 57 years) receiving 20 mg/kg/dose as a 4-hour infusion. The estimated mean AUC was 1,890 mcg x hour/mL with 51% coefficient of variation (CV) and Cmax was 307 mcg/mL with 47% CV.

Pregnancy And Lactation
Pregnancy

There are no adequate prospective studies of alglucosidase alfa in pregnant women. However, data from postmarketing reports and published case reports have not identified an alglucosidase alfa associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Individualize the treatment for Pompe disease during pregnancy to the affected woman; untreated Pompe disease may result in worsening disease symptoms in pregnant women. Daily administration of intravenous alglucosidase alfa up to 40 mg/kg/day in mice and rabbits (0.4 and 0.5 times the human steady-state exposure, respectively, at the recommended bi-weekly dose) during the period of organogenesis had no effects on embryo-fetal development. An increase in pup mortality during the lactation period was observed when alglucosidase alfa 40 mg/kg/day was administered every other day in mice during the period of organogenesis through lactation. Alglucosidase alfa should only be used during pregnancy if the potential benefit justifies the potential risk.[40712] Literature suggests the use of the drug is compatible with pregnancy.[64932] There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to alglucosidase alfa; information about the registry can be obtained at www.registrynxt.com or by calling 1-800-633-1610 or 1-800-745-4447 (extension 15500).[32280] [40711] [40712] [64932]

Alglucosidase alfa is present in human milk. In a case report, the enzymatic activity of alglucosidase alfa was detected in the breast milk of a lactating woman up to 24 hours after the end of intravenous administration. To minimize infant exposure, experts have recommended the nursing mother temporarily pump and discard breast milk produced during the 24 hours after drug administration. This case report, along with other literature, suggests that with careful management, the enzyme replacement therapy is compatible with breast-feeding. In another case report, a 38-year-old woman interrupted alglucosidase alfa therapy during pregnancy but restarted treatment with 20 mg/kg every 2 weeks during her first postpartum month. The patient expressed additional milk before alglucosidase therapy since she received strict advice that breast-feeding was not allowed for 24 hours after the completion of drug infusion; at 10 months, the nursing infant was developing normally. Data continue to be collected via a registry. Lactating women are encouraged to enroll in the Pompe Registry by calling 1-800-745-4447 (extension 15500) in the U.S. or online at www.lumizyme.com/patients/resources/the_pompe_registry.[32280] [40712] [64932]