Anaphylaxis has occurred with vestronidase alfa administration, as early as the first dose, therefore appropriate medical support should be readily available when administered. Closely observe patients during and for 60 minutes after vestronidase alfa infusion. Immediately discontinue the infusion if the patient experiences anaphylaxis.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Mepsevii: vestronidase alfa-vjbk 10 mg/5 mL (5 mL)
Mechanism of Action
Vestronidase alfa is a recombinant human beta-glucuronidase (GUS), which provides exogenous GUS enzyme for uptake into cellular lysosomes. Mannose-6-phosphate (M6P) residues on the oligosaccharide chains allow binding of the enzyme to cell surface receptors, leading to cellular uptake of the enzyme, targeting to lysosomes and subsequent catabolism of accumulated glycosaminoglycans (GAGs) in affected tissues.
Vd,ss: 260 ± 130 mL/kg (range: 97 to 598 mL/kg)
Proteolytic degradation into small peptides and amino acids
155 ± 37 minutes (range: 51 to 213 minutes)
Use: Labeled Indications
Mucopolysaccharidosis VII: Treatment of mucopolysaccharidosis VII (MPS VII, Sly syndrome).
Limitations of use: The effect of vestronidase alfa on the CNS manifestations of MPS VII has not been determined.
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Note: Premedicate with nonsedating antihistamines with/without antipyretics 30 to 60 minutes prior to the start of the infusion.
Mucopolysaccharidosis VII: IV: 4 mg/kg every 2 weeks
Refer to adult dosing.
Mucopolysaccharidosis VII (MPS VII, Sly syndrome): Note: Premedicate with nonsedating antihistamines with or without antipyretics 30 to 60 minutes prior to the start of the infusion.
Infants, Children, and Adolescents: IV: 4 mg/kg/dose every 2 weeks
Calculate dose (rounding to nearest whole vial) then remove vial(s) from refrigerator and allow to reach room temperature; do not heat, microwave, or shake vials. Solution in vials should be colorless to slightly yellow; discard if solution is discolored or contains particulate matter. Withdraw calculated dose (volume) from vials carefully; avoid excessive agitation and any air or frothing; use an 18-gauge needle to minimize bubbles in the solution. Slowly add to empty infusion bag to avoid agitation and generation of bubbles or turbulence. Dilute to a final 1:1 solution with NS; more than a 1:1 dilution may be used in patients who can tolerate additional volume. To ensure adequate distribution; gently rock the infusion bag without shaking the solution. Discard any unused product.
IV: Infuse IV over ~4 hours; infuse the first 2.5% of total volume over the first hour (accounting for any dead space in IV line); after the first hour, increase infusion rate (as tolerated) to complete infusion over the next 3 hours. Administer using an infusion set with an in-line low protein-binding 0.2 micron filter. Do not flush the line to avoid a rapid bolus of infused enzyme; due to the low infusion rate, additional NS may be added through a separate line (piggyback or Y tube) to maintain sufficient IV flow to prevent clotting or line blockage. Do not infuse other products in same IV line. Discontinue the infusion immediately if severe reaction occurs, including anaphylaxis. Observe patient during, and for 60 minutes following infusion.
May be an irritant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.
Store under refrigeration at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light. Following dilution use immediately; if this is not possible, the diluted solution may be stored up to 36 hours under refrigeration followed by up to 6 hours at room temperature ≤25°C (77°F). Infusion should be completed within 42 hours from time of dilution.
There are no known significant interactions.
Dermatologic: Skin rash (≤25%)
Gastrointestinal: Diarrhea (≤25%)
Hypersensitivity: Anaphylaxis (10% to 17%)
Immunologic: Antibody development (≤78%; neutralizing: ≤56%)
1% to 10%:
Cardiovascular: Peripheral edema (≤8%)
Dermatologic: Pruritus (≤8%)
Local: Swelling at injection site (≤8%)
Frequency not defined: Miscellaneous: Febrile seizures
Concerns related to adverse effects:
- Extravasation: Infusion site extravasation has been reported; infusion site swelling has also occurred.
- Hypersensitivity/anaphylactoid reactions: [US Boxed Warning]: Anaphylaxis has occurred with administration, as early as the first dose, therefore appropriate medical support should be readily available when administered. Manifestations included respiratory distress, cyanosis, decreased oxygen saturation, and hypotension. Closely observe patients during and for 60 minutes after infusion. Immediately discontinue the infusion if the patient experiences anaphylaxis. Consider the risks and benefits of re-administering vestronidase alfa following anaphylaxis; in clinical trials, patients experiencing anaphylaxis were able to tolerate subsequent infusions without recurrence of anaphylaxis.
Monitor for infusion/hypersensitivity reactions. Monitor infusion site.
Adverse events were not observed in animal reproduction studies.
- 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?)
- Have patient report immediately to prescriber blue/gray skin discoloration, nail discoloration, severe dizziness, or passing out (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 health care 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.