vestronidase alfa-vjbk (Rx)

<1%

Extravasation (0.5%)

Diarrhea (0.4%)

Rash (0.4%)

Anaphylaxis (0.4%)

Infusion site swelling (0.1%)

Peripheral swelling (0.1%)

Pruritus (0.1%)

Contraindications

None

Cautions

Anaphylaxis was reported in the clinical program; reactions occurred during infusion and were observed as early as the first dose; manifestations included respiratory distress, cyanosis, decreased oxygen saturation, and hypotension; administer under supervision of a healthcare professional with experience managing anaphylaxis (see Dosing Considerations and Black Box Warnings)

Pregnancy

No data are available regarding use in pregnant women

When administered to pregnant rats and rabbits during organogenesis, vestronidase alfa showed no maternal toxicity or adverse developmental outcomes at doses causing maternal serum exposures (AUC) up to 1.6 and 10 times, respectively for rats and rabbits, the exposure at the recommended human dose

Lactation

Unknown if present in either human or animal milk; the effects on the breastfed infant, or the effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Mucopolysaccharidosis VII (MPS VII or Sly syndrome) is a lysosomal disorder characterized by the deficiency of beta glucuronidase (GUS) that results in GAG accumulation in cells throughout the body, leading to multisystem tissue and organ damage

Recombinant human lysosomal GUS is intended to provide exogenous GUS enzyme for uptake into cellular lysosome; 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 GAGs in affected tissues

Absorption

Peak plasma concentration: 20 mcg/mL (range: 6.6-34.9 mcg/mL)

AUC: 3440 mcg·min/mL (range: 1130- 5820 mcg·min/mL)

Distribution

Vd: 260 mL/kg (range: 97-598 mL/kg)

Metabolism

Vestronidase alfa is a recombinant human enzyme and is therefore eliminated by proteolytic degradation into small peptides and amino acids

Elimination

Clearance: 1.3 mL/min/kg (range: 0.6 to 3.3 mL/min/kg)

Half-life: 155 minutes (range: 51-213 minutes)

No excretion studies have been conducted in humans; not expected to be eliminated through urine or feces

IV Compatibility

0.9% NaCl

Compatibility with other products has not been evaluated

IV Preparation

Determine total dose based on patient’s actual body weight (refer to prescribing information)

Remove required number of vials from refrigerator and allow them to reach room temperature; do not heat, microwave, or shake vials

Visually inspect solution for particulate matter and discoloration; slight flocculation (thin translucent fibers) may appear; solution should appear colorless to slightly yellow

Slowly withdraw the calculated dose using a large needle (eg, 18 gauge) to minimize bubbles in the solution

Add 0.9% NaCl equal to the drug volume to infusion bag; final solution should be a 1:1 solution of vestronidase alfa to 0.9% NaCl

Diluted solutions may be refrigerated (2-8°C [36-46°F]) for up to 36 hr and may be stored at room temperature (25°C [77°F]) for up to 6 hr

IV administration

Use an infusion set with an inline, low-protein binding 0.2 micron filter

Do not flush the line containing vestronidase alfa to avoid a rapid bolus of infused enzyme

Owing to 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

Do not infuse with other products in the infusion tubing

Use immediately after dilution and complete the infusion within 42 hr from the time of dilution

Discard any unused product

Rate of infusion

• First hour: Infuse 2.5% of the total volume; account for any dead space in the lines to ensure 2.5% of the total infusion volume is delivered
• Subsequent 3 hours: Infuse remaining volume (refer to prescribing information)

Storage

Unused vials: Store under refrigeration at 2-8°C (36-46°F)

Diluted solutions: Store in refrigerator at 2-8°C (36-46°F) for up to 36 hr and may be stored at room temperature at 25°C (77°F) for up to 6 hr

Do no freeze or shake

Protect from light