Chemical Name: β-Glucuronidase (synthetic human), homotetramer
Molecular Formula: C3308H4996N874O940S16
CAS Number: 1638194-78-1
Risk of life-threatening anaphylactic reactions as early as first dose. Appropriate medical support should be readily available.
Observe patients closely during and for ≥60 minutes after infusion. Immediately stop infusion if patient experiences anaphylaxis. (See Hypersensitivity Reactions under Cautions.)
Biosynthetic (recombinant DNA origin) form of human β-glucuronidase, a lysosomal enzyme that catabolizes glycosaminoglycans (GAGs).
Uses for Vestronidase Alfa-vjbk
Replacement therapy in patients with mucopolysaccharidosis VII (MPS VII, Sly syndrome); designated an orphan drug by FDA for use in this condition.
May improve motor function (e.g., increase walking distance) in some patients; however, effect on CNS manifestations not determined.
Vestronidase Alfa-vjbk Dosage and Administration
Prepare and administer under supervision of a clinician experienced in managing anaphylaxis.
To minimize risk of hypersensitivity reactions, administer a nonsedating antihistamine (with or without an antipyretic) 30–60 minutes prior to each infusion.
For solution and drug compatibility information, see Compatibility under Stability.
Administer by IV infusion.
Administer using an inline, low-protein-binding 0.2-µm filter.
Do not flush IV line to avoid rapid bolus; due to the slow rate of infusion, may administer additional 0.9% sodium chloride injection through a separate line to maintain sufficient IV flow and prevent clotting or blockage of the IV tubing.
Do not infuse through the same IV line with other drugs.
Vials contain no preservatives and are intended for single use only.
Vestronidase alfa-vjbk injection is a colorless to slightly yellow solution. Because the drug is a protein solution, slight flocculation (thin translucent fibers) may occur. Discard solution if discoloration or particulate matter is present.
Must dilute commercially available injection concentrate prior to administration.
Determine number of vials needed based on patient's actual weight and recommended dose of 4 mg/kg. Remove required number of vials from refrigerator and allow them to reach room temperature. Do not heat, microwave, or shake the vials.
Using a sufficiently large needle (e.g., 18 gauge), slowly withdraw calculated volume of vestronidase alfa-vjbk from the appropriate number of vials. Transfer drug to an empty infusion bag. Dilute with an equal volume of 0.9% sodium chloride injection (1:1 ratio). More than a 1:1 dilution ratio may be used if the patient can tolerate additional infusion volume, taking into consideration cardiac function and fluid status. Gently mix solution; avoid shaking or agitation.
Use immediately after dilution. If immediate use not possible, may store diluted solution at recommended conditions, but administration should be completed within 42 hours from the time of dilution. (See Storage under Stability.)
Rate of Administration
Administer over approximately 4 hours. In the first hour, infuse 2.5% of the total volume; increase infusion rate as tolerated to complete infusion over the subsequent 3 hours. Consult manufacturer's prescribing information for recommended infusion rate schedules. Account for dead space in the IV line to ensure that 2.5% of the total infusion volume is delivered during the first hour of infusion.
Closely observe patients for anaphylaxis during and for ≥60 minutes following administration. If a severe hypersensitivity reaction occurs, stop infusion immediately and initiate appropriate treatment. (See Hypersensitivity Reactions under Cautions.)
4 mg/kg by IV infusion once every 2 weeks.
4 mg/kg by IV infusion once every 2 weeks.
No special population dosage recommendations at this time.
Cautions for Vestronidase Alfa-vjbk
Hypersensitivity reactions, including life-threatening anaphylaxis, reported. (See Boxed Warning.) Manifestations include respiratory distress, cyanosis, decreased oxygen saturation, and hypotension.
Closely observe patients during and for ≥60 minutes after administration; ensure that appropriate medical support is readily available.
To minimize risk of hypersensitivity reactions, premedicate with a nonsedating antihistamine (with or without antipyretics). (See General under Dosage and Administration.)
If a severe hypersensitivity reaction occurs (e.g., anaphylaxis), stop infusion immediately and initiate appropriate treatment. Consider risks and benefits of retreatment following an anaphylactic reaction.
Other Warnings and Precautions
As with all therapeutic proteins, there is a potential for immunogenicity. Antibodies (including neutralizing antibodies) to vestronidase alfa-vjbk reported in most patients. However, presence of antibodies does not appear to affect urinary GAG concentrations, a pharmacodynamic measure of response.
No data on use in pregnant women. In animal studies, no maternal toxicity or adverse developmental outcomes observed.
Not known if distributed into milk. Effects of the drug on the breast-fed infant or on milk production also not known.
Consider known benefits of breast-feeding along with the woman's clinical need for the drug and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
Pediatric patients ≥5 months of age have been treated with vestronidase alfa-vjbk in clinical studies.
Clinical trials did not include patients ≥65 years of age. Not known if geriatric patients respond differently than younger patients.
Common Adverse Effects
Extravasation, diarrhea, rash, anaphylaxis, infusion site swelling, peripheral swelling, pruritus.
Interactions for Vestronidase Alfa-vjbk
No formal drug interaction studies to date.
Vestronidase Alfa-vjbk Pharmacokinetics
Reduction of urinary GAG excretion occurs rapidly within first 2 weeks of treatment.
Serum concentrations appear to increase in an approximately dose-proportional manner in the dose range of 1–4 mg/kg.
Serum concentrations in pediatric patients <5 years of age similar to those observed in older children and adults.
Not known whether vestronidase alfa-vjbk distributes into milk.
Does not cross blood-brain barrier.
Metabolized by proteolytic degradation into small peptides and amino acids.
Not expected to be eliminated through renal or fecal excretion.
155 minutes (range: 51–213 minutes).
Solution Concentrate for IV Infusion
2–8°C. Protect from light and freezing; do not shake.
Diluted solutions: If not used immediately, may store at 2–8°C for up to 36 hours, then at room temperature (up to 25°C) for up to 6 hours during administration.
For information on systemic interactions resulting from concomitant use, see Interactions.
Sodium chloride 0.9%
Biosynthetic (recombinant DNA origin) form of β-glucuronidase, a lysosomal enzyme that catabolizes GAGs (dermatan sulfate, chondroitin sulfate, and heparan sulfate).
Provides an exogenous source of β-glucuronidase, the deficient enzyme, in patients with MPS VII.
Enzymatic activity of vestronidase alfa-vjbk results in degradation of GAGs that accumulate and cause manifestations of the disease in patients with MPS VII.
Advice to Patients
Risk of anaphylaxis. Inform patients of the signs and symptoms of anaphylaxis, and advise patients to seek immediate medical care should such signs and symptoms occur.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
For injection, concentrate, for IV infusion only
2 mg/mL (10 mg)
AHFS DI Essentials™. © Copyright 2022, Selected Revisions May 20, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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