Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Naglazyme: 1 mg/mL (5 mL) [contains mouse (murine) and/or hamster protein, polysorbate 80]
Pharmacology
Mechanism of Action
Galsulfase is a recombinant form of N-acetylgalactosamine 4-sulfatase, produced in Chinese hamster cells. A deficiency of this enzyme leads to accumulation of the glycosaminoglycan dermatan sulfate in various tissues, causing progressive disease which includes decreased growth, skeletal deformities, upper airway obstruction, clouding of the cornea, heart disease, and coarse facial features. Exogenous replacement of this enzyme has been shown to improve mobility and physical function (measured by walking and stair-climbing).
Pharmacokinetics/Pharmacodynamics
Distribution
Vz: 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)
Use: Labeled Indications
Mucopolysaccharidosis VI: Replacement therapy in patients with mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) to improve walking and stair-climbing capacity.
Contraindications
There are no contraindications listed in the manufacturer's labeling
Dosage and Administration
Dosing: Adult
Note: Premedicate with antihistamines with/without antipyretics 30 to 60 minutes prior to the start of the infusion.
Mucopolysaccharidosis VI (MPS VI): IV: 1 mg/kg once weekly
Dosing: Pediatric
Mucopolysaccharidosis (MPS) VI: Note: Premedicate with antihistamines with or without antipyretics 30 to 60 minutes prior to infusion.
Infants: Limited data available: IV: 1 or 2 mg/kg/dose once weekly has been used in four infants (3 to 12 months); similar safety results to those of older patients were reported (Harmatz 2014)
Children and Adolescents: IV: 1 mg/kg/dose once weekly
Reconstitution
After calculating dose, round to the nearest whole vial to prepare infusion. Dilute in NS to a final volume of 250 mL (including volume of galsulfase). Slowly add galsulfase to infusion bag (use a low-protein binding container; compatibility in glass containers has not been studied). For patients with fluid restriction, the dose may be added to 100 mL NS (total volume is 100 mL is not necessary). Gently rotate bag to distribute. Do not shake or agitate, do not use filter needle.
Administration
IV: Infuse over at least 4 hours; infusions of a 250 mL total volume should 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 the remaining 3 hours. May extend infusion time up to 20 hours if infusion reactions occur. For patients requiring fluid restriction, solutions of 100 mL may be used with the rate adjusted 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.
Premedicate with antihistamines (with or without antipyretics) 30 to 60 minutes prior to infusion. In case of infusion-related reactions, decrease infusion rate or temporarily discontinue. Discontinue immediately if severe reaction occurs. Patients requiring supplemental oxygen or CPAP during sleep should have these treatments readily available in case of infusion-related or antihistamine-induced reaction.
Storage
Prior to reconstitution, store intact vials at 2°C to 8°C (36°F to 46°F). Do not freeze. Do not shake. Protect from light. Following dilution in NS, use immediately. May store under refrigeration if used within 48 hours from the time of preparation to the completion of infusion. Do not store solution for infusion at room temperature. Allow vials to reach room temperature prior to dilution. Do not keep vials at room temperature >24 hours prior to dilution. Do not heat or microwave vials.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
Note: Percentages reported are from a placebo-controlled study (39 patients, 19 on galsulfase); also included are adverse effects noted during other clinical studies.
Cardiovascular: Chest pain (16%), hypertension (11%)
Central nervous system: Pain (32%), chills (21%), absent reflexes (11%), malaise (11%), headache
Dermatologic: Skin rash (21%), pruritus, urticaria
Gastrointestinal: Abdominal pain (47%), gastroenteritis (11%), nausea, vomiting
Hypersensitivity: Angioedema
Neuromuscular & skeletal: Arthralgia (42%)
Ophthalmic: Conjunctivitis (21%), corneal opacity (increased, 11%)
Otic: Otalgia (42%), auditory impairment (11%)
Respiratory: Dyspnea (21%), pharyngitis (11%), nasal congestion (11%), apnea, laryngeal edema, respiratory distress
Miscellaneous: Antibody development (98%), infusion related reaction (56%), umbilical hernia (11%), fever
<1%, postmarketing, and/or case reports: Anaphylaxis, bradycardia, bronchospasm, cyanosis, erythema, hypotension, hypoxia, pallor, paresthesia, renal disease (membranous), respiratory failure, shock, spinal cord compression, tachycardia, tachypnea, thrombocytopenia
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Severe hypersensitivity reactions, including anaphylaxis, severe allergic reactions, shock, respiratory distress, dyspnea, bronchospasm, laryngeal edema, and hypotension have been reported during and within 24 hours after infusion. Immediate treatment for hypersensitivity reactions should be available during administration. Discontinue treatment immediately if signs or symptoms of anaphylaxis or severe allergic reactions occur; use caution upon rechallenge.
- Immune-mediated reactions: Severe type III immune-mediated reactions (eg, membranous glomerulonephritis) have occurred; monitor patients closely. Consider discontinuation of treatment if signs or symptoms occur; use caution with readministration (some patients have been successfully re-challenged with close supervision).
- Infusion reactions: Infusion-related reactions have been commonly reported; may be sporadic and/or severe. Serious/severe infusion reactions have included laryngeal edema, apnea, respiratory distress, dyspnea, angioedema, and anaphylactoid reaction, pyrexia, chest pain, rash, urticaria, and conjunctivitis; other reactions included chills, nausea, vomiting, pruritus, erythema, abdominal pain, hypertension, hypotension, headache, tremor, and cough. Reactions began as early as week 1 and as late as week 146 of treatment. Many patients experienced recurrent infusion reactions during multiple infusions, though not always in consecutive weeks. Patients should be premedicated with antihistamines and/or antipyretics prior to infusion; evaluate airway prior to therapy (due to possible effects of antihistamine use). Symptoms typically abated with slowing or temporary interruption of the infusion and administration of additional antihistamines, antipyretics, and, occasionally, corticosteroids. Most patients were able to complete their infusions. Subsequent infusions were managed with a slower rate of administration, treatment with additional prophylactic antihistamines, and, in the event of a more severe reaction, treatment with prophylactic corticosteroids. Discontinue treatment immediately and initiate appropriate treatment if severe reaction occurs; use caution with readministration (consider the risks/benefits of readministering following a severe reaction).
Disease-related concerns:
- Acute febrile/respiratory illness: Consider delaying treatment in patients with an acute febrile or respiratory illness.
- Patients at risk for fluid overload: Use with caution in patients who are at risk of fluid overload (patients ≤20 kg, underlying respiratory disease, or compromised cardiopulmonary function); may cause heart failure. Monitor patients closely.
- Sleep apnea: Use with caution in patients with sleep apnea (sleep apnea is common in patients with MPS VI); antihistamine pretreatment may increase the risk of apneic episodes. Evaluate airway patency prior to initiation of treatment; apnea treatment options should be readily available during the infusion and with antihistamine premedication.
- Spinal/cervical cord compression: Worsening and new-onset spinal/cervical cord compression (SCC) has been reported (SCC with resultant myelopathy is a known and anticipated serious complication of MPS VI). Monitor patients for signs and symptoms of SCC (eg, back pain, limb paralysis below the level of compression, urinary and fecal incontinence) and provide appropriate clinical care.
Special populations:
- Adults: Studies did not include patients >29 years of age.
Dosage form specific issues:
- Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Monitoring Parameters
Monitor for infusion/hypersensitivity reactions; signs and symptoms of spinal/cervical cord compression.
Pregnancy
Pregnancy Considerations
Information related to the use of galsulfase in pregnancy is limited (Stewart 2016).
Pregnancy may exacerbate symptoms of mucopolysaccharidosis VI, leading to adverse maternal and fetal outcomes.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience abdominal pain, joint pain, ear pain, cough, nausea, vomiting, sore throat, stuffy nose, or loss of strength and energy. Have patient report immediately to prescriber signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), shortness of breath, excessive weight gain, severe dizziness, passing out, chest pain, severe headache, chills, vision changes, trouble hearing, eye pain, severe eye irritation, difficulty moving, back pain, urinary or leaking of stool, tremors, or swelling of arms or legs (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
