(el oh SUL fase AL fa)
Mucopolysaccharidosis type IVA: Treatment of mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome)
There are no contraindications listed in the manufacturers labeling.
Life-threatening anaphylactic reactions have occurred in some patients during elosulfase alfa infusions. Anaphylaxis, presenting as cough, erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash, dyspnea, chest discomfort, and gastrointestinal symptoms (eg, nausea, abdominal pain, retching, vomiting) in conjunction with urticaria, have been reported to occur during elosulfase alfa infusions, regardless of duration of the course of treatment. Closely observe patients during and after elosulfase alfa 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.
Note: Premedicate with antihistamines with or without antipyretics 30 to 60 minutes prior to infusion.
Mucopolysaccharidosis type IVA (MPS IVA): IV: 2 mg/kg once weekly
Note: Premedicate with antihistamines with or without antipyretics 30 to 60 minutes prior to infusion.
Mucopolysaccharidosis type IVA (MPS IVA):
US labeling: Children ≥5 years and Adolescents: IV: Refer to adult dosing
Canadian labeling: Infants ≥9 months, Children, and Adolescents: IV: Refer to adult dosing (has not been studied >52 weeks in children <5 years of age).
There are no dosage adjustments provided in manufacturer 's labeling.
There are no dosage adjustments provided in manufacturer 's labeling.
Dilute calculated dose in NS to a final volume of 100 mL (for patients weighing <25 kg) or 250 mL (for patients weighing ≥25 kg). Gently rotate to distribute. Do not shake or agitate. Use immediately. Vials are for single use only; discard any unused product.
Administer using a low protein-binding infusion set with in-line low protein-binding 0.2 micrometer filter. Pretreatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to infusion.
Patients <25 kg: Infuse 100 mL solution at 3 mL/hour for the first 15 minutes. If well-tolerated, increase to 6 mL/hour for the next 15 minutes. If well-tolerated, increase rate every 15 minutes in 6 mL/hour increments; maximum infusion rate: 36 mL/hour. The total volume of the infusion should be delivered over ≥3.5 hours.
Patients ≥25 kg: Infuse 250 mL solution at 6 ml/hour for the first 15 minutes. If well-tolerated, increase to 12 mL/hour for the next 15 minutes. If well-tolerated, increase rate every 15 minutes in 12 mL/hour increments; maximum infusion rate: 72 mL/hour. The total volume of the infusion should be delivered over ≥4.5 hours.
The infusion can be slowed, temporarily stopped, or discontinued if a hypersensitivity reaction occurs. Discontinue immediately if severe reaction occurs. Do not infuse with other products in the infusion tubing. Administration should be completed within 48 hours from time of dilution.
Prior to use, store intact vials under refrigeration at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F); do not freeze or shake. Protect from light. Following dilution in NS, use immediately. If unable to use immediately, may store for up to 24 hours under refrigeration followed by up to 24 hours at 23 ‚ °C to 27 ‚ °C (73 ‚ °F to 81 ‚ °F) during administration.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Vimizim: 5 mg/5 mL (5 mL) [contains mouse (murine) and/or hamster protein]
There are no known significant interactions.
Monitor for infusion/hypersensitivity reactions; signs/symptoms of spinal or cervical compression.
>10%:
Central nervous system: Headache (26%)
Gastrointestinal: Vomiting (31%), nausea (24%), abdominal pain (21%)
Hypersensitivity: Hypersensitivity reaction (19%)
Miscellaneous: Fever (33%)
1% to 10%:
Central nervous system: Chills (10%), fatigue (10%)
Hypersensitivity: Anaphylaxis (8%; presenting as cough, erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash, dyspnea, chest discomfort, and gastrointestinal symptoms)
Immunologic: Immunogenicity
Concerns related to adverse effects:
- Antibody formation: All patients developed anti-drug antibodies and neutralizing antibodies during clinical trials; it is unknown if presence of antibodies is related to a higher risk of infusion reactions or clinical efficacy treatment effect, respectively.
- Hypersensitivity/anaphylactoid reactions: [U.S. Boxed Warning]: Serious hypersensitivity reactions, including life-threatening anaphylactic reactions have occurred, regardless of treatment course duration. Anaphylaxis may present as abdominal pain, chest discomfort, cough, cyanosis, dyspnea, erythema, flushing, hypotension, nausea, rash, retching, throat tightness, urticaria, and vomiting. Monitor closely during and after infusion. Appropriate medical support should be readily available. Patients with acute respiratory disease are at risk of serious acute exacerbation or respiratory compromise due to hypersensitivity; additional monitoring may be required. Discontinue immediately if anaphylactic or acute reaction occurs. Patients experiencing initial severe or refractory reactions may need prolonged monitoring. Use caution with readministration.
- Infusion reactions: Infusion-related reactions have been reported; may be sporadic and/or severe. Hypersensitivity reactions may occur as early as 30 minutes from the start of infusion and have also been reported as late as 6 days after infusion; reactions may occur as late as the 47th infusion. Patients should be premedicated with antihistamines with or without antipyretics prior to infusion; evaluate airway prior to therapy (due to possible effects of antihistamine use). In case of reaction, decrease the rate of infusion, temporarily discontinue the infusion, and/or administer additional antipyretics/antihistamines and possibly corticosteroids. Discontinue treatment immediately if severe reaction occurs; use caution with readministration.
Disease-related concerns:
- Acute febrile/respiratory illness: Consider delaying treatment in patients with an acute febrile or respiratory illness; may be at increased risk of life-threatening complications from hypersensitivity reactions.
- Sleep apnea: Use with caution in patients with sleep apnea; antihistamine pretreatment may increase the risk of apneic episodes. Apnea treatment options (eg, supplemental oxygen or continuous positive airway pressure) should be readily available.
- Spinal/cervical cord compression: Patients with MPA IVA may experience spinal/cervical cord compression (SCC) as a part of their disease. Monitor patients for signs and symptoms of SCC (eg, back pain, limb paralysis, urinary and fecal incontinence).
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Adverse events were observed in some animal reproduction studies. Mucopolysaccharidosis type IVA (MPS IVA) has the potential to cause adverse events in both the mother and fetus. A pregnancy registry is available for women who may be exposed to elosulfase alfa for the treatment of MPS IVA during pregnancy (MARS@bmrn.com or 1-800-983-4587).
Elosulfase alfa is a recombinant form of N-acetylgalactosamine-6-sulfatase, produced in Chinese hamster cells. A deficiency of this enzyme leads to accumulation of the glycosaminoglycan (GAG) substrates (keratan sulfate and chondroitin-6-sulfate) in tissues, causing cellular, tissue and organ dysfunction. Elosulfase alfa provides the exogenous enzyme (N-acetylgalactosamine-6-sulfatase) that is taken into lysosomes and thereby increases the catabolism of the GAG substrates (eg, keratan sulfate and chondroitin-6-sulfate).
Vd: Week 0: 396 mL/kg; Week 22: 650 mL/kg
Week 0: 172 minutes; Week 22: 202 minutes
Week 0: ~8 minutes; Week 22: ~36 minutes
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache or loss of strength and energy. Have patient report immediately to prescriber signs of infusion reaction (cough, skin redness, tightness in throat, flushing, blue skin, severe dizziness, passing out, shortness of breath, angina, vomiting, or severe abdominal pain), swelling of arm or leg, cough, back pain, difficulty moving, or urinary or fecal incontinence (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.