Galsulfase

What is galsulfase used for?

Galsulfase is a prescription medicine that is  used to treat mucopolysaccharidosis VI.

Description

NAGLAZYME is a formulation of galsulfase, which is a purified human enzyme that is produced by recombinant DNA technology in a Chinese hamster ovary cell line.  Galsulfase (glycosaminoglycan N–acetylgalactosamine 4-sulfatase, EC 3.1.6.12) is a lysosomal enzyme 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 kDa.  The recombinant protein consists of 495 amino acids and possesses six asparagine‑linked glycosylation sites, four of which carry a bis‑mannose–6–phosphate residue for specific cellular recognition.  Post-translational modification of Cys53 produces the catalytic amino acid residue, Cα-formylglycine, which is required for enzyme activity.  NAGLAZYME has a specific activity of approximately 70 units per mg of protein content.  One activity unit is defined as the amount of enzyme required to convert 1 micromole of 4-methylumbelliferyl sulfate to 4-methylumbelliferone and free sulfate per minute at 37°C.

NAGLAZYME is intended for intravenous infusion and is supplied as a sterile, nonpyrogenic, colorless to pale yellow, clear to slightly opalescent solution that must be diluted with 0.9% Sodium Chloride Injection, USP, prior to administration.  NAGLAZYME is supplied in clear Type I glass 5 mL vials.  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 in a 5 mL extractable solution with pH of approximately 5.8.  NAGLAZYME does not contain preservatives. Each vial is for single use only.

 Mechanism of Action

Mucopolysaccharide storage disorders are caused by the deficiency of specific lysosomal enzymes required for the catabolism of GAG.  MPS VI is characterized by the absence or marked reduction in N–acetylgalactosamine 4-sulfatase.  The sulfatase activity deficiency results in the accumulation of the GAG substrate, dermatan sulfate, throughout the body.  This accumulation leads to widespread cellular, tissue, and organ dysfunction.  NAGLAZYME is intended to provide an exogenous enzyme that will be taken up into lysosomes and increase the catabolism of GAG.  Galsulfase uptake by cells into lysosomes is most likely mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of galsulfase to specific mannose-6-phosphate receptors.

Before taking galsulfase, tell your doctor:

• If you are allergic to galsulfase; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take galsulfase with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take galsulfase?

• Tell all of your health care providers that you take galsulfase. This includes your doctors, nurses, pharmacists, and dentists.
• Some people have had very bad allergic reactions during the infusion or within 24 hours of the infusion. Sometimes, these have been life-threatening. Talk with the doctor.
• Tell your doctor if you are pregnant, plan on getting pregnant, or are breast-feeding. You will need to talk about the benefits and risks to you and the baby.

How is galsulfase best taken?

Use galsulfase as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.
• Other drugs may be given before galsulfase to help avoid side effects.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

What are the side effects of galsulfase that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Signs of high or low blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Chest pain or pressure.
• Fever or chills.
• Change in eyesight, eye pain, or very bad eye irritation.
• Change in hearing.
• Not able to move.
• Back pain.
• Not able to control bladder.
• Not able to control stools.
• Shakiness.

What are some other side effects of galsulfase?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Stomach pain.
• Joint pain.
• Ear pain.
• Cough.
• Upset stomach or throwing up.
• Headache.
• Nose or throat irritation.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out galsulfase?

• If you need to store galsulfase at home, talk with your doctor, nurse, or pharmacist about how to store it.

SRC: NLM .