Naglazyme

About Naglazyme:

• Naglazyme (Galsulfase) is a normal variant form of the polymorphic human enzyme, N–acetylgalactosamine 4-sulfatase which is produced by recombinant DNA technology in a Chinese hamster ovary cell line. 
• N–acetylgalactosamine 4-sulfatase (glycosaminoglycan N–acetylgalactosamine 4-sulfatase, EC 3.1.6.12) is a lysosomal hydrolase that catalyzes the cleavage of the sulfate ester from terminal N–acetylgalactosamine 4-sulfate residues of glycosaminoglycans (GAG) chondroitin 4-sulfate and dermatan sulfate.
• Galsulfase is a glycoprotein with a molecular weight of approximately 56 kD. The recombinant protein is comprised of 495 amino acids and contains six asparagine-linked glycosylation sites, four of which carry a bis mannose-6-phosphate mannose7 oligosaccharide for specific cellular recognition.
• Post-translational modification of Cys53 produces the catalytic amino acid residue, Cα-formylglycine, which is required for enzyme activity and is conserved in all members of the sulfatase enzyme family.
• Naglazyme has a specific activity of approximately 70 U/mg protein content. One activity unit (U)
• is defined as the amount of enzyme required to convert 1 µmole of 4-methylumbelliferyl sulfate to 4-methylumbelliferone and free sulfate per minute at 37°C.
• Naglazyme, for intravenous infusion, is supplied as a sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted in 0.9% Sodium Chloride Injection, USP, prior to administration. 
• The solution in each vial contains a nominal galsulfase concentration of 1 mg/mL (expressed as protein concentration) at a pH of approximately 5.8. 
• The extractable volume of 5 mL from each vial provides 5 mg galsulfase, 43.8 mg sodium chloride, 6.20 mg sodium phosphate monobasic monohydrate, 1.34 mg sodium phosphate dibasic heptahydrate, and 0.25 mg polysorbate 80. Naglazyme does not contain preservatives; vials are for single use only.

Strength: 

The recommended dose regimen of Naglazyme is 1 mg/kg of body weight administered once weekly as an intravenous (IV) infusion.

Recommended Dosage:

• Pretreatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to initiation of infusion.
• The total amount of the infusion should be delivered in no less than 4 hours. 
• The solution should be reconstituted in 0.9% sodium chloride injection, to a final volume of 250 mL and administered by controlled IV infusion using an infusion pump. 
• The initial infusion should be at the rate of 6 mL/h for the first hour and if the infusion is tolerated well, it may be increased to 80 mL/h for the remaining 3 hours.
• The infusion time can be extended up to 20 hours if infusion reactions occur.
• For patients 20 kg and under who are prone to fluid overload, dilution should be done in a volume of 100 mL. 
• The infusion rate (mL/min) should be decreased so that the total infusion duration remains no less than 4 hours.
• Each vial of Naglazyme contains 5 mg of Galsulfase in 5 mL of solution and is used for single use only and should be used under an aseptic technique.

Warnings & Precautions

• Naglazyme infusion causes potential infusion reactions, therefore patients should receive antihistamines with or without antipyretics prior to administration.
• If severe reactions occur, it should be discontinued immediately and proper treatment should be initiated.
• Sleep apnea is common in patients with MPS VI and antihistamine pretreatment may increase the risk of same. Airway evaluation should be considered prior to treatment. 
• Consider delaying infusions in patients who present who have acute febrile/respiratory illness.

Common Naglazyme Side Effects

• Urticaria of the face and neck
• Bronchospasm
• Respiratory distress
• Apnea
• Headache
• Fever
• Arthralgia
• Vomiting
• Upper respiratory infections
• Abdominal pain
• Diarrhea
• Ear pain
• Cough
• Otitis media

Use in Specific Population

Pregnancy: It’s a category B agent and no adequate and well-controlled studies in pregnant women have been evaluated. 

Pediatric use: Safety and efficacy in patients younger than 5 years of age have not been evaluated.

Storage and Handling

• Naglazyme is stored under refrigeration at 2°C to 8°C (36°F to 46°F). 
• The product should not be frozen or shaken.

• Not to be used after the expiration date on the vial. 
• This product does not contain any preservatives and the diluted solution should be used immediately. If immediately not used, then diluted solution should be refrigerated at 2°C to 8°C (36°F to 46°F).
• The storage after dilution should not exceed 48 hours from the time of preparation to 
• Room temperature storage of diluted preparation is not recommended.