Dosage & Administration
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Lumizyme Prescribing Information
Hypersensitivity Reactions Including Anaphylaxis
Patients treated with enzyme replacement therapies have experienced life-threatening hypersensitivity reactions, including anaphylaxis. Anaphylaxis has occurred during the early course of enzyme replacement therapy and after extended duration of therapy. Initiate LUMIZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment. If a severe hypersensitivity reaction (e.g., anaphylaxis) occurs, discontinue LUMIZYME and immediately initiate appropriate medical treatment, including use of epinephrine. Inform patients of the symptoms of life-threatening hypersensitivity reactions, including anaphylaxis and to seek immediate medical care should symptoms occur [see Warnings and Precautions (5.1)].
Immune-Mediated Reactions
Immune-mediated reactions presenting as proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following LUMIZYME treatment. Monitor patients for the development of systemic immune-mediated reactions involving skin and other organs while receiving LUMIZYME [see Warnings and Precautions (5.3)].
Risk of Acute Cardiorespiratory Failure
Infantile-onset Pompe disease (IOPD) patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to fluid overload and require additional monitoring [see Warnings and Precautions (5.4)].
LUMIZYME® is a hydrolytic lysosomal glycogen-specific enzyme indicated for patients with Pompe disease (acid α-glucosidase [GAA] deficiency).
Recommendations prior to LUMIZYME Treatment
- Administration of LUMIZYME should be supervised by a healthcare provider knowledgeable in the management of hypersensitivity reactions including anaphylaxis [see Warnings and Precautions (5.1)].
- Initiate LUMIZYME in a healthcare setting with appropriate medical monitoring and support measures, including access to cardiopulmonary resuscitation equipment [see Warnings and Precautions (5.1)].
- Prior to LUMIZYME administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions (5.1, 5.2)].
- LUMIZYME must be reconstituted and diluted prior to use [see Dosage and Administration (2.3)].
- Appropriate medical monitoring and support measures, including cardiopulmonary resuscitation equipment, should be readily available during LUMIZYME administration [see Warnings and Precautions (5.1)].
Recommended Dosage and Administration
- The recommended dosage of LUMIZYME is 20 mg/kg body weight administered every 2 weeks as an intravenous infusion. The initial infusion rate should be no more than 1 mg/kg/hour [see Dosage and Administration (2.5)].
Missed Dose
If one or more doses are missed, restart LUMIZYME treatment as soon as possible, maintaining the 2-week interval between infusions thereafter.
Reconstitution and Dilution Instructions
Reconstitute and dilute LUMIZYME in the following manner.
Use aseptic technique during preparation. Do not use filter needles during preparation.
Reconstitute the Lyophilized Powder
- Determine the number of LUMIZYME vials to be reconstituted based on the actual body weight in kg and the recommended dose of 20 mg/kg. Round the number of vials up to the next whole number.
- Remove the required number of LUMIZYME vials from the refrigerator and allow the vials to sit for approximately 30 minutes at room temperature 20°C to 25°C (68°F to 77°F) prior to reconstitution.
- Reconstitute each vial by slowly injecting 10.3 mL of Sterile Water for Injection, down the inside wall of each vial. Avoid adding the Sterile Water for Injection to the vial forcefully or directly onto the lyophilized powder to minimize foaming.
- Gently tilt and roll each vial. Do not invert, swirl, or shake the vial. Each vial will yield a concentration of 5 mg/mL of LUMIZYME. The total extractable dose per vial is 50 mg per 10 mL.
- Visually inspect the reconstituted solution in the vials for particulate matter and discoloration. Discard if particles are present or the solution is discolored. The reconstituted solution may occasionally contain some LUMIZYME particles (typically less than 10 in a vial) in the form of thin white strands or translucent fibers subsequent to the initial inspection. This may also happen following dilution for infusion. These particles have been shown to contain LUMIZYME and may appear after the initial reconstitution step and increase over time. Studies have shown that these particles are removed via in-line filtration without having a detectable effect on the purity or strength.
Dilute the Reconstituted Solution
- Select and prepare an appropriate size 0.9% Sodium Chloride for Injection infusion bag with quantity sufficient of 0.9% Sodium Chloride for Injection to obtain the recommended total infusion volume per table 1 based on patient weight and dilute.
- Slowly withdraw the required volume of reconstituted solution from the LUMIZYME vial(s). Avoid foaming in the syringe. Discard any unused reconstituted solution remaining in the vial.
- Remove airspace from the prepared 0.9% Sodium Chloride for Injection infusion bag to minimize particle formation due to the sensitivity of LUMIZYME to air-liquid interfaces.
- Inject the LUMIZYME reconstituted solution slowly and directly into the port of the prepared 0.9% Sodium Chloride for Injection infusion bag. Avoid foaming and introducing air in the infusion bag.
- Gently invert or massage the infusion bag to mix the solution. Do not shake. After dilution, the solution will have a final concentration of 0.5 to 4 mg/mL of LUMIZYME.
Storage Instructions for the Reconstituted and Diluted Product
- The reconstituted and diluted solution should be administered without delay. Storage of the reconstituted solution at room temperature is not recommended.
- If immediate use is not possible, the reconstituted and diluted solution is stable for up to 24 hours refrigerated at 2°C to 8°C (36°F to 46°F).
- The reconstituted and diluted LUMIZYME solution should be protected from light.
- Do not freeze or shake.
Administration Instructions
- The total volume of infusion is determined by the patient's body weight and should be administered over approximately 4 hours.
- Administer LUMIZYME using an in-line low protein binding 0.2-micron filter.
- Infusions should be administered in a step-wise manner using an infusion pump. The initial infusion rate should be no more than 1 mg/kg/hr. The infusion rate may be increased by 2 mg/kg/hr every 30 minutes, after patient tolerance to the infusion rate is established, until a maximum rate of 7 mg/kg/hr is reached.
- Vital signs should be obtained at the end of each step. If the patient is stable, LUMIZYME may be administered at the maximum rate of 7 mg/kg/hr until the infusion is completed.
- The infusion rate may be slowed or temporarily stopped in the event of mild to moderate hypersensitivity reactions. In the event of anaphylaxis or severe hypersensitivity reaction, immediately discontinue administration of LUMIZYME and initiate appropriate medical treatment. 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.
- Do not infuse LUMIZYME in the same intravenous line with other products. Discard any unused product.
| Patient Weight Range | Total infusion volume | Step 1 1 mg/kg/hr | Step 2 3 mg/kg/hr | Step 3 5 mg/kg/hr | Step 4 7 mg/kg/hr |
|---|---|---|---|---|---|
| Infusion Rate in mL/hr | |||||
| 1.25 to 2.5 kg | 25 mL | 1.25 | 3.75 | 6.25 | 6.6 |
| 2.6 to 10 kg | 50 mL | 3 | 8 | 13 | 18 |
| 10.1 to 20 kg | 100 mL | 5 | 15 | 25 | 35 |
| 20.1 to 30 kg | 150 mL | 8 | 23 | 38 | 53 |
| 30.1 to 35 kg | 200 mL | 10 | 30 | 50 | 70 |
| 35.1 to 50 kg | 250 mL | 13 | 38 | 63 | 88 |
| 50.1 to 60 kg | 300 mL | 15 | 45 | 75 | 105 |
| 60.1 to 100 kg | 500 mL | 25 | 75 | 125 | 175 |
| 100.1 to 120 kg | 600 mL | 30 | 90 | 150 | 210 |
| 120.1 to 140 kg | 700 mL | 35 | 105 | 175 | 245 |
| 140.1 to 160 kg | 800 mL | 40 | 120 | 200 | 280 |
| 160.1 to 180 kg | 900 mL | 45 | 135 | 225 | 315 |
| 180.1 to 200 kg | 1,000 mL | 50 | 150 | 250 | 350 |
For injection: 50 mg of LUMIZYME is supplied as a sterile, nonpyrogenic, white to off-white, lyophilized cake or powder in a single-dose vial for reconstitution. After reconstitution, the resultant solution concentration is 5 mg/mL.
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to LUMIZYME during pregnancy. Pregnant women and women of reproductive potential should be encouraged to enroll in the Pompe patient registry. The registry will monitor the effect of LUMIZYME on pregnant women and their offspring. For more information, visit www.registrynxt.com or call 1-800-745-4447, extension 15500.
Risk Summary
Data from postmarketing reports and published case reports with alglucosidase alfa use in pregnant women have not identified a LUMIZYME-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The continuation of treatment for Pompe disease during pregnancy should be individualized to the pregnant woman. Untreated Pompe disease may result in worsening disease symptoms in pregnant women (see Clinical Considerations).
Reproduction studies performed in mice and rabbits at doses resulting in exposures up to 0.4 or 0.5 times the human steady-state AUC (area under the plasma concentration-time curve), respectively, during the period of organogenesis revealed no evidence of effects on embryo-fetal development. In mice there was an increase in pup mortality during lactation at maternal exposures 0.4 times the human steady-state AUC (see Data).
The background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Disease-associated Maternal and/or Embryo-fetal Risk
Untreated Pompe disease has been associated with worsening respiratory and musculoskeletal symptoms in some pregnant women.
Data
Animal Data
All reproductive studies included pretreatment with diphenhydramine to prevent or minimize hypersensitivity reactions. The effects of alglucosidase alfa were evaluated based on comparison to a control group treated with diphenhydramine alone. Daily intravenous administration of alglucosidase alfa up to 40 mg/kg in mice and rabbits (0.4 and 0.5 times the human steady-state AUC, respectively, at the recommended biweekly dose) during the period of organogenesis had no effects on embryo-fetal development. Administration of 40 mg/kg intravenously every other day in mice (0.4 times the human steady-state AUC at the recommended biweekly dose) during the period of organogenesis through lactation produced an increase in mortality of offspring during the lactation period.
Lactation
Risk Summary
Available published literature suggests the presence of alglucosidase alfa in human milk. There are no reports of adverse effects of alglucosidase alfa on the breastfed infant. There is no information on the effects of alglucosidase alfa on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for LUMIZYME and any potential adverse effects on the breastfed child from LUMIZYME or from the underlying maternal condition.
Lactating women with Pompe disease treated with LUMIZYME should be encouraged to enroll in the Pompe disease registry [see Use in Specific Populations (8.1)].
Clinical Considerations
A lactating woman may consider interrupting breastfeeding, pumping and discarding breast milk during treatment and for 24 hours after LUMIZYME administration in order to minimize drug exposure to a breastfed infant.
Pediatric Use
The safety and effectiveness of LUMIZYME has been established in pediatric patients with Pompe disease [see Adverse Reactions (6.2)].The use of LUMIZYME for this pediatric indication is supported by evidence from an adequate and well-controlled trial in 57 treatment-naive pediatric patients with IOPD treated with alglucosidase alfa, aged 0.2 month to 3.5 years at first infusion, (Trials 1, 2, and 3) [see Clinical Studies (14.1)] and 90 adult and pediatric patients with LOPD in a randomized, double-blind, placebo-controlled trial including 2 patients 16 years of age or less [see Clinical Studies (14.2)].
Anaphylaxis, hypersensitivity reactions, and acute cardiorespiratory failure have occurred in pediatric patients [see Boxed Warning, Warnings and Precautions (5.1, 5.3)]. Additionally, cardiac arrhythmia and sudden cardiac death have occurred in pediatric patients during general anesthesia for central venous catheter placement [see Warnings and Precautions (5.4)].
Geriatric Use
The randomized, double-blind, placebo-controlled study of alglucosidase alfa did not include sufficient numbers (n=4) of patients aged 65 years and over to determine whether they respond differently from younger adult patients [see Clinical Studies (14.1)].
None.