Naglazyme (Galsulfase) is a recombinant human N-acetylgalactosamine-4 sulfatase. It is used as an enzyme replacement therapy available as an injection for the treatment of mucopolysacharidosis.

Naglazyme (Galsulfase) Uses:

• Mucopolysaccharidosis VI:

  • It is used as a Replacement therapy in patients with mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) to improve walking and stair-climbing capacity.

Naglazyme (Galsulfase) Dose in Adults

Note: it should be premeditated 30 to 60 minutes prior to start the infusion with antihistamines with/without antipyretics.

Naglazyme (Galsulfase) Dose in the treatment of Mucopolysaccharidosis VI (MPS VI):

• IV:
  • 1 mg/kg once a week.

Naglazyme (Galsulfase) Dose in Childrens

Naglazyme (Galsulfase) Dose in the treatment of Mucopolysaccharidosis (MPS) VI:

Note:

• Premedicate 30 to 60 minutes prior to infusion with antihistamines with or without antipyretics.

• Infants: Limited data available:

  • IV: 1 or 2 mg/kg/dose once a week, used in four infants of age about 3 to 12 months;
  • similar safety results in old age  patients were reported (Harmatz 2014)

• Children and Adolescents:

  • IV: 1 mg/kg/dose once a week.

Pregnancy Risk Factor B

• Animal reproduction studies have not shown any adverse events.

Galsulfase use during breastfeeding:

• It is unknown whether galsulfase in breast milk is excreted or not.
• Manufacturer recommended caution for women who are breastfeeding.
• The pregnancy registry also includes data on breastfeeding mothers who have used galsulfase to treat MPS VI.

Naglazyme Dose in Kidney Disease:

•  No dosage adjustments provided in the manufacturer's labeling.

Naglazyme Dose in Liver disease:

•  No dosage adjustments provided in the manufacturer's labeling.

Note:

• The Percentages reported are from a placebo-controlled study (39 patients, 19 on galsulfase).
• It also include the adverse effects that are noted during other clinical studies.

Side effects of Naglazyme (Galsulfase):

• Cardiovascular:

  • Chest Pain
  • Hypertension

• Central Nervous System:

  • Pain
  • Chills
  • Absent Reflexes
  • Malaise
  • Headache

• Dermatologic:

  • Skin Rash
  • Pruritus
  • Urticaria

• Gastrointestinal:

  • Abdominal Pain
  • Gastroenteritis
  • Nausea
  • Vomiting

• Hypersensitivity:

  • Angioedema

• Neuromuscular & Skeletal:

  • Arthralgia

• Ophthalmic:

  • Conjunctivitis
  • Corneal Opacity

• Otic:

  • Otalgia
  • Auditory Impairment

• Respiratory:

  • Dyspnea
  • Pharyngitis
  • Nasal Congestion
  • Apnea
  • Laryngeal Edema
  • Respiratory Distress

• Miscellaneous:

  • Antibody Development
  • Infusion Related Reaction
  • Umbilical Hernia
  • Fever

Contraindications to Naglazyme (Galsulfase):

• There are no contraindications in the labeling of the manufacturer

Warnings and precautions

• Hypersensitivity

  • Infusions have been associated with severe hypersensitivity reactions including anaphylaxis and shock, as well as respiratory distress and hypotension.
  • You should immediately treat hypersensitivity reactions during administration.
  • You should immediately discontinue any treatment if you experience severe allergic reactions or anaphylaxis.

• Reactions that are immune-mediated

  • There have been severe type III immune-mediated reactions (eg membranous Glucomitis)
  • If you notice any signs or symptoms, discontinue treatment. Be careful with readministration.
  • Some patients have been able to re-challenge themselves with close supervision.

• Infusion reactions

  • There have been many reports of infusion-related reactions. These can be either mild or severe.
  • Infusion reactions that are severe and serious include laryngeal swelling, respiratory distress,apnea and dyspnea as well as anaphylactoid reactions,anaphylactoid reactions,anaphylactoid reactions,anaphylactoid reactions,anaphylactoid reactions,apnea and dyspnea and chest pain,pyrexia and urticaria.
  • Other reactions include chills, nausea and vomiting, pruritus and headaches
  • The reactions could have started as early as week 1, or as late at week 146.
  • Recurrent infusion reactions were common in patients who received multiple infusions. However, not all in the same week.
  • Before infusions with antihistamines or antipyretics, patients should be premedicated.
  • Preventive therapy for airway problems (due to antihistamine effects).
  • Patients usually feel better after a temporary or slow interruption of their infusion and the administration of additional antihistamines and antipyretics.
  • You can manage subsequent infusions with either a slower administration or with prophylactic Antihistamines. If you have a severe reaction, you can use prophylactic Corticosteroids.
  • If severe reactions occur, discontinue treatment immediately and begin the appropriate treatment.
  • Re-administration should be done with caution. Consider the benefits and risks of administering again after a severe reaction.

• Acute febrile/respiratory disease:

  • Patients with acute febrile illness or respiratory disease should not be delayed in getting treatment.

• Fluid overload is a risk to patients

• Fluid overload can lead to heart failure in patients at high risk, such as patients with a weight of 20kg, patients with underlying respiratory diseases, or patients who have compromised cardiopulmonary function.
• Pay attention to your patients.

• Sleep Apnea

  • Patients with sleep apnea should be cautious (sleep disorder VI is more common in these patients).
  • Pretreatment with antihistamines may increase the likelihood of developing apneic episodes.
  • Before starting treatment, evaluate your airway patency. Apnea treatment options must be available during infusions and with antihistamine medication premedication.

• Compression of cervical/spinal cords

  • There have been reports of new-onset and worsening spinal/cervical compressions (SCC).
  • SCC and myelopathy are a well-known and expected serious side effect of MPS VI.
  • Patients should be monitored for back pain, limb paralysis, and urinary and fecal problems (signs and symptoms of SCC).

Monitoring parameters:

Monitor for infusion and hypersensitivity reactions; signs and symptoms of spinal/cervical cord compression.

How to administer Naglazyme (Galsulfase)?

Intravenous:

• Infuse over at least 4 hours.
•  Infusions of a 250 mL  begin at a rate of 6 mL/hour for the first hour, if tolerated, may increase the rate of infusion to 80 mL/hour for remaining 3 hours.
• If infusion reaction occurs may extend infusion time up to 20 hours.
• For patients requiring fluid restriction, solutions of 100 mL may be used or adjust the rate to infuse over at least 4 hours.
• Administer using infusion pump and PVC (low protein-binding) infusion set with in-line low protein-binding 0.2 micrometer filter.
• Prior to infusion Premedicate with antihistamines (with or without antipyretics) 30 to 60 minutes.
• Discontinue infusion temporarily or decrease infusion rate in case of infusion-related reactions.
• Discontinue immediately if severe reaction occurs.
• Patients who require supplemental oxygen or CPAP during sleep should have these treatments available (in case of infusion-related or antihistamine-induced reaction).

Mechanism of action of Naglazyme (Galsulfase):

• Galsulfase is a recombinant form of N-acetylgalactosamine 4-sulfatase, produced in Chinese hamster cells.
• This enzyme is required to cause accumulation of the glycosaminoglycan desmatan sulfate (in various tissues) that causes progressive disease.
• Exogenous replacement has been shown to improve mobility and function (measured by walking or stair-climbing).

Note: Data based on mixed patient population of children ≥5 years and adults <29 years.

Distribution:

• Week 1: 103 mL/kg (range: 56 to 323 mL/kg).
• Week 24: 69 mL/kg (range: 59 to 2,799 mL/kg)

Half-life elimination:

• Week 1: Median 9 minutes (range: 6 to 21 minutes).
• Week 24: Median 26 minutes (range: 8 to 40 minutes)

International Brands of Galsulfase:

• Naglazyme
• Naglazyzme

Galsulfase Brand Names in Pakistan:

No Brands Available in Pakistan.