Vestronidase alfa - a recombinant human B-glucuronidase

Vestronidase alfa is a recombinant form of human beta-glucuronidase, which provides exogenous glucuronidase enzyme for cellular lysosomal uptake.

It is indicated for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome).

Limitation in use due to: The effect of vestronidase alfa on the CNS manifestations of MPS VII has not been determined.

Vestronidase alfa Dose in Adults:

Note: Premedicate with nonsedating antihistamines with/without antipyretics 30 to 60 minutes prior to the start of the infusion.

Dose in the treatment of Mucopolysaccharidosis VII:

Dose in the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome):

Note:

Premedicate with nonsedating antihistamines with or without antipyretics 30 - 60 minutes prior to the start of the infusion.

Infants, Children, and Adolescents:
- 4 mg/kg/dose Intravenous every 2 weeks

Vestronidase alfa use during breastfeeding:

It is unknown whether breast milk contains estrogen.
According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants, the benefits to the infant and the benefits to the mother.

Dose adjustment based on hepatic function is unlikely to be necessary as vestronidase alfa is degraded by proteolytic enzymes that are not restricted to hepatic tissue.

Warnings and Precautions

Extravasation:
- Reports of infusion site extravasation or swelling have been made.
Hypersensitivity/ anaphylactoid reactions - [US Boxed Warning]
- Anaphylaxis can occur with the administration of any dose.
- Therefore, it is important to have medical assistance readily available for those who administer the medication.
- These manifestations included respiratory distress, hypotension, decreased oxygen saturation and cyanosis.
- Observe patients closely during and 60 minutes following infusion.
- If the patient experiences anaphylaxis, stop the infusion immediately.
- Consider the risks and advantages of readingministering vestronidase Alfa after anaphylaxis.
- Clinical trials showed that patients suffering from anaphylaxis could tolerate subsequent infusions with no recurrence.

Monitor for hypersensitivity reactions. Monitor the infusion site for extravasation.

Infuse intravenously over 4 hours.
Infuse the first 2.5% of total volume over the first hour.
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 the 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.
Infusion of other products in the same IV line should be avoided.
If severe reaction(including anaphylaxis) occurs, discontinue the infusion immediately.
Patients should be observed, and for 60 minutes following infusion.

It may be an irritant. For that purpose, ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.

Vestronidase alfa is a recombinant form of human beta-glucuronidase, which provides exogenous glucuronidase enzyme for cellular lysosomal uptake.
Receptors at the cell's surface bind to the enzyme through residues of Mannose-6phosphate (M6P), which leads to cellular uptake and catabolism (GAG) of accumulated glycosaminoglycans in the affected tissues.

Distribution: V : 260 ± 130 mL/kg (range: 97 to 598 mL/kg)

Metabolism: Proteolytic degradation into small peptides and amino acids

Half-life elimination: 155 ± 37 minutes (rangeing from 51 to 213 minutes)