Dosing and uses of Vimizim (elosulfase alfa)
Adult dosage forms and strengths
concentrated intravenous solution
- 1mg/mL (in 5mg/5mL single use vials [requires dilution])
Morquio A Syndrome
Indicated for enzyme replacement therapy for Morquio A syndrome (mucopolysaccharidosis Type IVA [MPS IVA])
2 mg/kg IV infused over a minimum of 3.5-4.5 hr
Dosing Considerations
Inform patients of the Morquio A Registry established in order to better understand the variability and progression of the disease in the population as a whole, and to monitor and evaluate long-term treatment effects of elosulfase alfa
For more information, contact MARS@bmrn.com or call 1-800-983-4587
Administration
Pretreat with antihistamines (with or without antipyretics) 30-60 minutes before initiating infusion
Pediatric dosage forms and strengths
concentrated intravenous solution
- 1mg/mL (in 5mg/5mL single use vials [requires dilution])
Morquio A Syndrome
Enzyme replacement therapy pending FDA approval for Morquio A syndrome (mucopolysaccharidosis Type IVA [MPS IVA])
<5 years: Safety and efficacy not established
≥5 years: 2 mg/kg IV infused over a minimum of 3.5-4.5 hr
Dosing Considerations
Inform patients of the Morquio A Registry established in order to better understand the variability and progression of the disease in the population as a whole, and to monitor and evaluate long-term treatment effects of elosulfase alfa
For more information, contact MARS@bmrn.com or call 1-800-983-4587
Administration
Pretreat with antihistamines (with or without antipyretics) 30-60 minutes before initiating infusion
Vimizim (elosulfase alfa) adverse (side) effects
>10%
Pyrexia (33%)
Vomiting (31%)
Headache (26%)
Nausea (24%)
Abdominal pain (21%)
Hypersensitivity, including anaphylaxis (18.7%)
Chills (10.3%)
Fatigue (10.3%)
1-10%
Anaphylaxis (7.7%)
Warnings
Black box warnings
Anaphylaxis
- Life-threatening anaphylactic reactions reported during IV infusion
- Anaphylaxis, presenting as cough, erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash, dyspnea, chest discomfort, and gastrointestinal symptoms (eg, nausea, abdominal pain, retching, and vomiting) in conjunction with urticaria, have been reported to occur during infusions, regardless of duration of the course of treatment
- Closely observe patients during and after administration and be prepared to manage anaphylaxis
- Inform patients of the signs and symptoms of anaphylaxis and have them seek immediate medical care should symptoms occur Patients with acute respiratory illness may be at risk of serious acute exacerbation of their respiratory compromise due to hypersensitivity reactions, and require additional monitoring
Contraindications
None
Cautions
Anaphylaxis reported and may occur as early as 30 minutes from the start of infusion and up to 3 hr after completing the infusion (see Black box warnings)
Increased risk of acute respiratory complications; monitor patients with acute febrile or respiratory illness at the time of infusion (higher risk of life-threatening complications from hypersensitivity reaction)
Sleep apnea is common in patients with MPS IVA, evaluate airway patency before initiating treatment with elosulfase alfa
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown if distributed in human breast milk, use with caution; present in milk from treated rats
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Vimizim (elosulfase alfa)
Mechanism of action
Replaces deficient enzyme N-acetylgalactosamine-6 sulfatase (GALNS) to minimize progressive multisystemic manifestations of Morquio A syndrome
Sulfatase activity deficiency results in the accumulation of the GAG substrates, KS and C6S, in the lysosomal compartment of cells throughout the body; the accumulation leads to widespread cellular, tissue, and organ dysfunction
Enzyme replacement provides the exogenous enzyme GALNS that will be taken up into the lysosomes and increase catabolism of GAGs KS and C6s
Absorption
All measurements at treatment week 22
AUC: 577 min•mcg/mL
Peak plasma time: 202 minutes
Peak plasma concentration: 4.04 mcg/mL
Distribution
All measurements at treatment week 22
Vd: 7.08 mL/min/kg
Elimination
All measurements at treatment week 22
Half-life: 35.9 minutes
Administration
IV Compatibilities
Do not infuse with other products in the infusion tubing
Compatibility with other products has not been evaluated
IV Preparation
Determine the number of vials to be diluted based on the individual patient’s weight and the recommended dose of 2 mg/kg
The solution should be clear to slightly opalescent and colorless to pale yellow when diluted
Do not use if the solution is discolored or if there is particulate matter in the solution
Note that a diluted solution with slight flocculation (eg, thin translucent fibers) is acceptable for administration
Avoid agitation during preparation; gently rotate the bag to ensure proper distribution
Do NOT shake the solution
Dilute the calculated dose to a final volume of 100 mL or 250 mL using 0.9% NaCL
Final volume is based on the patient’s weight
- <25 kg: 100 mL
- ≥25 kg: 250 mL
IV Administration
Administer diluted solution IV using a low-protein binding infusion set equipped with a low-protein binding 0.2 micrometer in-line filter
The infusion rate may be slowed, temporarily stopped, or discontinued for that visit in the event of hypersensitivity reactions
Weight <25 kg
- Diluted volume totals 100 mL
- 3 mL/hr IV initially for the first 15 minutes, and if tolerated, increased to 6 mL/hr for the next 15 minutes
- If this rate is tolerated, then the rate may be increased every 15 minutes in 6 mL/hr increments, not to exceed 36 mL/hr
- The total volume of the infusion should be delivered over a minimum of 3.5 hr
Weight ≥25 kg
- Diluted volume totals 250 mL
- 6 mL/hr IV initially for the first 15 minutes, and if tolerated, increased to 12 mL/hr for the next 15 minutes
- If this rate is tolerated, then the rate may be increased every 15 minutes in 12 mL/hr increments, not to exceed 72 mL/hr
- The total volume of the infusion should be delivered over a minimum of 4.5 hr
Storage
Contains no preservatives; discard partially used vials
Do not freeze
Do not shake
Protect from light
Unopened vials
- Store refrigerated between 2-8°C [36-46°F]) in original carton and protect from light
Diluted solution
- If immediate use is not possible, store refrigerated for up to 24 hr at 2-8°C (36-46°F) followed by up to 24 hr at 23-27°C (73-81°F) during administration
- Administration should be completed within 48 hr from the time of dilution
