VESTRONIDASE ALFA-vjbk INJECTION 
Pronounciation
- (ves-TRON-i-dase AL-fa VJBK)
Trade Name(s)
- Mepsevii
For patient comfort, the administration of a nonsedating antihistamine (e.g., cetirizine or loratadine), with or without an antipyretic medication (e.g., acetaminophen or ibuprofen), is recommended 30 to 60 minutes before the start of the infusion.
4 mg/kg as an IV infusion over 4 hours every 2 weeks. Infuse the first 2.5% of the total volume over the first hour. After the first hour, increase the infusion rate as tolerated in order to complete the infusion over the next 3 hours; see Rate of Administration.
See Usual Dose.
No dose adjustment recommended.
Available as a colorless to slightly yellow liquid in a single-dose vial containing 10 mg/5 mL (2 mg/mL). Determine the number of vials to be diluted based on the patient’s actual weight and the recommended dose of 4 mg/kg using the following calculations:
Total dose (mg) = Patient’s weight (kg) × 4 mg/kg
Total number of vials = Total dose (mg) ÷ 10 mg/vial
A 40-kg adolescent requiring 4 mg/kg would require a dose of 160 mg. The number of vials required would be 16. If necessary, round up to the next whole vial. After patient is weighed and the appropriate dose is calculated, remove sufficient vials from refrigerator and allow them to reach RT. Do not heat, microwave, or shake vials.
Volume (mL) of calculated dose = Total dose (mg) ÷ 2 mg/mL concentration
The total volume in the above example is 80 mL. The final solution should be a 1:1 dilution with NS. More than a 1:1 dilution may be used if additional infusion volume can be tolerated, taking into consideration the patient’s cardiac function and fluid status. Select an empty infusion bag based on the total volume of the final solution as a 1:1 dilution. Thin translucent fibers may occur in the vestronidase alfa-vjbk solution. Discard if solution is discolored or contains particulate matter. Using an appropriately sized syringe and a sufficiently large needle (18 gauge) to minimize bubbles in the solution, slowly withdraw the calculated volume of the vestronidase alfa-vjbk solution from the appropriate number of vials. Avoid excessive agitation and any air or frothing. Slowly add the vestronidase alfa-vjbk solution to the infusion bag, taking care to avoid agitation and to ensure liquid-to-liquid contact without generating bubbles or turbulence. Slowly add NS equal to the volume of vestronidase alfa-vjbk solution to the infusion bag. Gently rock the infusion bag to ensure proper distribution of vestronidase alfa-vjbk. Do not shake the solution.
Use of an in-line, low–protein-binding, 0.2-micron filter required.
Before use, refrigerate vials at 2° to 8° C (36° to 46° F). Do not freeze or shake. Protect from light. Use solution immediately after dilution, and complete the infusion within 42 hours from the time of dilution. If immediate use is not possible, diluted solution may be refrigerated for up to 36 hours followed by up to 6 hours at room temperature up to a maximum of 25° C (77° F). Discard any unused product.
Manufacturer states, “Do not infuse with other products in the infusion tubing. Compatibility with other products has not been evaluated.”
Infuse the first 2.5% of the total volume over the first hour. After the first hour, increase the infusion rate as tolerated in order to complete the infusion over the next 3 hours. Use an infusion set equipped with an in-line, low–protein-binding, 0.2-micron filter to administer. Administer with an automated infusion pump or see prescribing information for a weight-based infusion rate schedule. Prime infusion line with vestronidase alfa-vjbk solution to ensure 2.5% of the total infusion volume is delivered to the patient during the first hour of the infusion. To avoid a rapid bolus of infused enzyme, do not flush the line containing vestronidase alfa-vjbk solution. Because of the low infusion rate, additional saline may be added through a separate line (piggyback or Y-tube) to maintain sufficient intravenous flow to prevent clotting or line blockage.
A recombinant form of human lysosomal beta-glucuronidase (GUS). It is intended to provide exogenous GUS enzyme for uptake into cellular lysosomes. Mannose-6-phosphate (M6P) residues on the oligosaccharide chains allow the enzyme to bind to cell surface receptors, leading to cellular uptake of the enzyme, targeting to lysosomes, and subsequent catabolism of accumulated GAGs (glycosaminoglycans) in affected tissues. Results in reduction of urinary excretion of GAGs (including chondroitin sulfate and dermatan sulfate), which is sustained with continued treatment. Elimination half-life is 155 ± 37 minutes (range: 51 to 213 minutes). Eliminated by degradation into small peptides and amino acids. Not expected to be eliminated through renal or fecal excretion.
Treatment of mucopolysaccharidosis type VII (MPS VII, Sly syndrome) in pediatric and adult patients. MPS VII is a lysosomal disorder characterized by a deficiency of GUS enzyme, which results in GAG accumulation in cells throughout the body and leads to multisystem tissue and organ damage.
Effect of vestronidase alfa-vjbk on the CNS manifestations of MPS VII has not been determined.
Administered under the direction of a physician knowledgeable in its use in a facility with the ability to monitor the patient and respond to any medical emergency.■ Hypersensitivity reactions, including anaphylaxis, have been reported; see Monitor and Antidote. ■ A therapeutic protein product. Patients have developed anti–vestronidase alfa-vjbk antibodies (ADA). Neutralizing antibodies have also been detected. There is no correlation between ADA titer and neutralizing antibody development. In clinical trials, the presence of ADA titer did not appear to affect reduction in the pharmacodynamic marker urinary glycosaminoglycan (uGAG).
Observe closely for a hypersensitivity reaction, including anaphylaxis, during the infusion and for a minimum of 60 minutes after the infusion. May occur as early as the first dose. S/S included cyanosis, decreased oxygen saturation, hypotension, and respiratory distress. Discontinue infusion immediately for a severe systemic reaction, including anaphylaxis.
Lifelong enzyme replacement therapy is required. ■ Promptly report S/S of a hypersensitivity reaction (e.g., chills, dizziness, fatigue, fever, headache, itching, nausea, rash, shortness of breath, wheezing). Reactions may occur during or after infusion. ■ Pretreatment with antihistamines and/or antipyretics may be used to prevent or lessen reactions.
No data available for use in pregnant women. Consider benefit versus possible risk. ■ No data available on the presence of vestronidase alfa-vjbk in human milk, the effects on breast-fed infants, or the effects on milk production. Consider risk versus benefit. ■ Safety and effectiveness for use in pediatric patients under 18 years of age have been established.
Not known if elderly patients respond differently than do younger patients. Clinical trials did not include patients 65 years of age and over.
Anaphylaxis, diarrhea, infusion site extravasation, infusion site swelling, peripheral swelling, pruritus, and rash are most common. Anaphylaxis is the most serious reaction reported.
Keep physician informed of side effects; may be treated symptomatically if indicated. Based on the severity of the reaction, temporarily slow, interrupt, or discontinue the infusion for clinical evidence of a hypersensitivity reaction. Discontinue infusion immediately for a severe systemic reaction and/or anaphylaxis and treat with oxygen, epinephrine, antihistamines, vasopressors, corticosteroids, albuterol, IV fluids, and ventilation equipment as indicated. Patients have tolerated subsequent infusions without recurrence of anaphylaxis. Resuscitate as necessary.