Myozyme

Name: Myozyme

How supplied

Dosage Forms And Strengths

MYOZYME 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

MYOZYME 50 mg vials are supplied as a sterile, nonpyrogenic, white to off-white lyophilized cake or powder. MYOZYME 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 MYOZYME under refrigeration between 2° to 8°C (36° to 46°F). Do not use MYOZYME 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 MYOZYME solution should be protected from light. DO NOT FREEZE OR SHAKE.

NDC 58468-0150-1

MYOZYME is manufactured and distributed by: Genzyme Corporation, 500 Kendall Street, Cambridge, MA 02142. Revised: May 2014

Pharmacology

Mechanism of Action

Recombinant acid alpha-glucosidase (GAA)

Carbohydrate groups on GAA molecule bind to mannose-6-phosphate receptors, then GAA is transported into cell where it undergoes proteolytic cleavage resulting in increased enzymatic glycogen cleavage

Pharmacokinetics

Half-Life: 2-3 hr

Peak Plasma Concentration: 162±31 mcg/m

AUC: 811±141 mcg-hr/mL

Vd: 80-110 mL/kg

Clearance: 20-30 mL/hr/kg

Administration

IV Incompatibilities

Do not mix with other drugs in same infusion line

IV Preparation

Do not use filter needles during preparation

Determine number of vials required for dose (20 mg/kg)

Remove the required number of vials from the refrigerator and allow them to reach room temperature prior to reconstitution (approximately 30 minutes)

Reconstitute each vial by slowly injecting 10.3 mL sterile water for injection

Avoid foaming & forceful addition of fluid

Protect reconstituted solution from light

Discard if discoloration or particulate matter present

Dilute (slowly) reconstituted solution in 0.9% NaCl to final concentration of 0.5-4 mg/mL

Filter diluted solution through 0.2 micron low protein-binding, in-line filter during administration

IV Administration

Administer by IV infusion over ~4 hr

1 mg/kg/hr IV infusion initially, may increase by 2 mg/kg/hr q30 min; not to exceed 7 mg/kg/hr

Recommended infusion volume:

  • 1.25-10 kg: 50 mL
  • 10.1-20 kg: 100 mL
  • 20.1-30 kg: 150 mL
  • 30.1-35 kg: 200 mL
  • 35.1-50 kg: 250 mL
  • 50.1-60 kg: 300 mL
  • 60.1-100 kg: 500 mL
  • 100.1-120 kg: 600 mL
  • 120.1-140 kg: 700 mL
  • 140.1-160 kg: 800 mL
  • 160.1-180 kg: 900 mL
  • 180.1-200 kg: 1000 mL

Storage

Unreconstituted vials: Store at 2-8°C (36-46°F)

Protect from freezing

Do not shake

Reconstituted/diluted solution stable up to 24 hr at 2-8°C (36-46°F)

Protect from light

What should i avoid while receiving alglucosidase alfa (lumizyme, myozyme)?

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

  • Electrocardiogram (ECG or EKG)
  • Electrophysiology Test
  • Wolff-Parkinson-White Syndrome

Myozyme Dosage and Administration

General

  • May administer antipyretics and/or antihistamines prior to alglucosidase alfa infusion.1

  • If a severe reaction occurs, consider immediate discontinuance of the infusion and initiate appropriate medical treatment.1

  • Use caution when readministering alglucosidase alfa in patients who have experienced infusion reactions.1

Administration

Administer by IV infusion.1

IV Administration

Administer by IV infusion using an infusion pump and a 0.2-mcm low-protein-binding inline filter.1

Alglucosidase alfa particles (typically less than 10 in a vial) may be present in reconstituted alglucosidase alfa solutions in the form of thin white strands or translucent fibers subsequent to the initial inspection or following dilution for infusion; studies have shown that these particles are removed via inline filtration and do not have a detectable effect on the purity or strength of alglucosidase alfa solutions.1 Do not use solution if opaque particles or discoloration are observed immediately following reconstitution of the drug.1

Do not infuse alglucosidase alfa infusions simultaneously through the same IV line with other drugs.1

Reconstitution

Allow vial containing 50 mg of alglucosidase alfa to reach room temperature (over about 30 minutes), then reconstitute by slowly injecting 10.3 mL of sterile water for injection to the inside wall of the vial to yield a final concentration of 5 mg/mL (total extractable amount per vial: 50 mg [10 mL]).1 To avoid forceful impact of the water for injection on the powder and to avoid foaming, inject the sterile water for injection slowly by drop-wise addition down the inside of the vial and not directly unto the lyophilized cake.1

Gently roll and tilt vial until the lyophilized cake or powder has dissolved; do not invert, swirl, or shake vial.1

Vials are for single use only; discard partially used vials of reconstituted solution.1

Dilution

Immediately dilute reconstituted alglucosidase alfa in 0.9% sodium chloride injection to provide a final concentration of 0.5–4 mg/mL and a total volume of 50–1000 mL (depending on patient weight, see table below).1

Slowly withdraw the appropriate dose of reconstituted solution from each vial avoiding foaming; remove airspace from infusion bag to minimize particle formation.1 Inject reconstituted alglucosidase alfa solution slowly and directly into the sodium chloride infusion solution, not into any remaining airspace within the infusion bag; avoid foaming.1

Gently invert or massage bag containing final solution to mix contents; do not shake.1

Rate of Administration

Administer by IV infusion over approximately 4 hours using an infusion pump.1 Initial infusion rate should not exceed 1 mg/kg per hour.1 May increase infusion rate in stepwise fashion in increments of 2 mg/kg per hour every 30 minutes after patient tolerance to the infusion rate is established, to a maximum rate of 7 mg/kg per hour.1 Obtain vital signs at the end of each stepwise increase in the infusion rate.1

May decrease (or temporarily discontinue) infusion rate, if infusion-related reactions occur.1 (See Infusion Reactions under Cautions.)

Recommended Infusion Volumes and Rates1

Step 1

Step 2

Step 3

Step 4

Patient Weight Range (kg)

Total Infusion Volume (mL)

1 mg/kg per hour (mL/hour)

3 mg/kg per hour (mL/hour)

5 mg/kg per hour (mL/hour)

7 mg/kg per hour (mL/hour)

1.25–10

50

3

8

13

18

10.1–20

100

5

15

25

35

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

1000

50

150

250

350

Dosage

Dosage of alglucosidase alfa is expressed in mg.1 The specific activity of alglucosidase alfa is 3–5 U/mg, with 1 unit defined as the amount of activity that results in the hydrolysis of 1 mcmol of a synthetic substrate per minute under specified assay conditions.1

Pediatric Patients

Pompe Disease Infantile-onset Pompe Disease IV

Infants and children 1 month to 3.5 years of age: 20 mg/kg by IV infusion once every 2 weeks.1

Prescribing Limits

Pediatric Patients

Pompe Disease Infantile-onset Pompe Disease IV

Maximum infusion rate: 7 mg/kg per hour.1

Special Populations

No special population dosage recommendations at this time.1

Interactions for Myozyme

No formal drug interaction studies to date.1

Indications and Usage for Myozyme

Myozyme® (alglucosidase alfa) [see Description (11)]  is a lysosomal glycogen-specific enzyme indicated for use in patients with Pompe disease (GAA deficiency). Myozyme has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of Myozyme in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy [see Clinical Studies (14) ].

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 Myozyme. 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 Counseling Information (17)].

Labor and Delivery

Information on the effect of Myozyme on labor and delivery is unknown. Pregnant women are encouraged to enroll in the Pompe Registry [see Patient Counseling Information (17)].

Nursing Mothers

It is not known whether Myozyme is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Myozyme is administered to a nursing woman.  Nursing women are encouraged to enroll in the Pompe Registry [see Patient Counseling Information (17)].

Pediatric Use

Pediatric patients aged 1 month to 3.5 years at time of first infusion have been treated with Myozyme in clinical trials [see Clinical Studies (14)]. Other open-label clinical trials of Myozyme have been performed in older pediatric patients ranging from 2 to 16 years at the initiation of treatment (juvenile-onset Pompe disease); however, the risks and benefits of Myozyme treatment have not been established in the juvenile-onset Pompe disease population.

Geriatric Use

Clinical studies did not include any subjects aged 65 years and older. It is not known whether they respond differently than younger subjects [see Clinical Studies (14)].

Patient Counseling Information

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 alglucosidase alfa. The Pompe Registry will also monitor the effects of alglucosidase alfa on pregnant women and their offspring [see Use in Specific Populations (8)]. Patients and their caregivers are encouraged to participate in the Pompe Registry and should be advised that their participation is voluntary and may involve long-term follow-up. For information regarding the registry program visit www.pomperegistry.com or call 1-800-745-4447.

General Clinical Recommendations

Patients and caregivers should be informed that anaphylactic reactions, severe allergic reactions, and immune mediated reactions have been observed in some patients having received Myozyme infusions. Patients and caregivers should also be warned of the risk for acute cardiorespiratory failure, cardiac arrhythmias, and infusion reactions.[see Boxed Warning and Warnings and Precautions (5)].

Myozyme is manufactured and distributed by:
Genzyme Corporation
500 Kendall Street
Cambridge, MA 02142
1-800-745-4447

US License Number: 1596
Myozyme, LUMIZYME and GENZYME are registered trademarks of Genzyme Corporation.

Package Carton – Principle Dispay Panel – 50 mg Carton

Package contains one vial of

Myozyme®

(alglucosidase alfa)

50 mg

Store Refrigerated At 2-8°C (36-46°F)

Do Not Freeze or Shake

Protect From Light

Contains No Preservatives

For Single Use Only

No U.S. Standard of Potency

See package insert for

dosage and administration.

Myozyme 
alglucosidase alfa injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:58468-0150
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ALGLUCOSIDASE ALFA (ALGLUCOSIDASE ALFA) ALGLUCOSIDASE ALFA 5 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
MANNITOL  
POLYSORBATE 80  
SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE  
SODIUM PHOSPHATE, DIBASIC, HEPTAHYDRATE  
Packaging
# Item Code Package Description
1 NDC:58468-0150-1 1 VIAL, SINGLE-USE (1 VIAL) in 1 CARTON
1 10.5 mL in 1.0 VIAL, SINGLE-USE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA125141 06/19/2010
Labeler - Genzyme Corporation (025322157)
Establishment
Name Address ID/FEI Operations
Genzyme Corporation (45 NYA) 968278916 API MANUFACTURE(58468-0150), ANALYSIS(58468-0150)
Establishment
Name Address ID/FEI Operations
Genzyme Corporation (51 NYA) 968278874 API MANUFACTURE(58468-0150), ANALYSIS(58468-0150)
Establishment
Name Address ID/FEI Operations
Genzyme Corporation (76 NYA) 943130096 ANALYSIS(58468-0150)
Establishment
Name Address ID/FEI Operations
Genzyme Northborough Operations Center 050424395 LABEL(58468-0150), PACK(58468-0150)
Establishment
Name Address ID/FEI Operations
BioReliance (US) 175174176 ANALYSIS(58468-0150)
Establishment
Name Address ID/FEI Operations
Bionique Testing Laboratories 108684523 ANALYSIS(58468-0150)
Establishment
Name Address ID/FEI Operations
Genzyme (Waltham) 078456891 ANALYSIS(58468-0150)
Establishment
Name Address ID/FEI Operations
Genzyme Corporation (Allston) 926029653 ANALYSIS(58468-0150)
Establishment
Name Address ID/FEI Operations
Genzyme Flanders BVBA (Cipalstraat) 372153895 ANALYSIS(58468-0150)
Establishment
Name Address ID/FEI Operations
Genzyme Ireland Ltd 985127419 MANUFACTURE(58468-0150), ANALYSIS(58468-0150), LABEL(58468-0150)
Establishment
Name Address ID/FEI Operations
Genzyme Ltd. 229522842 LABEL(58468-0150), PACK(58468-0150)
Establishment
Name Address ID/FEI Operations
ILS Limited 777381963 ANALYSIS(58468-0150)
Revised: 05/2014   Genzyme Corporation
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