Dosing and uses of Naglazyme (galsulfase)
Adult dosage forms and strengths
injectable solution
- 1mg/mL
Mucopolysaccharidosis VI
1 mg/kg IV infusion qWeek
Pretreat with antihistamines with or without antipyretics 30-60 minutes before infusion
Pediatric dosage forms and strengths
injectable solution
- 1mg/mL
Mucopolysaccharidosis VI
<5 years: Safety & efficacy not established
>5 years: 1 mg/kg IV infusion qWeek
Pretreat with antihistamines with or without antipyretics 30-60 minutes before infusion
Naglazyme (galsulfase) adverse (side) effects
>10%
Abdominal pain (53%)
Ear pain (42%)
Conjunctivitis (21%)
Dyspnea (21%)
Rigors (21%)
Chest pain (16%)
Pharyngitis (16%)
Areflexia (11%)
Face edema (11%)
Gastroenteritis (11%)
HTN (11%)
Increased corneal opacification (11%)
Malaise (11%)
Nasal congestion (11%)
Umbilical hernia (11%)
Frequency not defined
Bronchospasm
Erythema
Tachycardia
Thrombocytopenia
Tachypnea
Shock
Cyanosis
Hypoxia
Warnings
Contraindications
None listed in the manufacturer's labeL
Cautions
Anaphylaxis and severe allergic reactions have been observed during and up to 24 hr after infusion; some reactions were life-threatening and included anaphylaxis, shock, respiratory distress, dyspnea, bronchospasm, laryngeal edema, and hypotension
Type III immune complex-mediated reactions, including membranous glomerulonephritis, observed with enzyme replacement therapies
Caution in patients susceptible to fluid volume overload (eg, weight ≤20 kg, acute underlying respiratory illness, compromised cardiac and/or respiratory function) because CHF may result
Because of the potential for infusion reactions, patients should receive antihistamines with or without antipyretics prior to infusion; infusion reactions may still occur despite of premedication; decrease rate of infusion if it occurs or discontinue immediately if reaction is severe; use caution with readministration
Sleep apnea is common in patients with MPS VI and antihistamine pretreatment may increase the risk of apneic episodes
Spinal or cervical cord compression (SCC) with resultant myelopathy is a known and serious complication of MPS VI; SCC is expected to occur in the natural history of the disease, including in patients on galsulfase; there are postmarketing reports of onset or worsening of SCC requiring decompression surgery
Consider postponing treatment in patients with acute febrile or respiratory illness
Excess agitation of solutioni prior to or after dilution may denature and inactivate galsulfase
A registry has been created to track adverse effects, and monitor therapeutic responses during long-term treatment; may contact 1-800-983-4587 or at www.naglazyme.com/en/clinical-resources/surveillance-program.aspx
Pregnancy and lactation
Pregnancy category: B
Lactation: Excretion in milk unknown; use with caution
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.
Pharmacology of Naglazyme (galsulfase)
Mechanism of action
Recombinant N-acetylgalactosamine-4-sulfatase enzyme replacement that prevents the accumulation of the glycosaminoglycan dermatan sulfate in various tissues that could cause progressive disease including decreased growth, skeletal deformities, clouding of the cornea, upper airway obstruction, coarse facial features, and heart disease
Pharmacokinetics
Peak Plasma (mean): Week 1: 0.8 mcg/mL; Week 24: 1.5 mcg/mL
Half-Life: 6-21 min (Week 1); 8-40 min (Week 24)
Vd: 56-323 mL/kg (week 1); 59-2799 mL/kg (week 24)
Clearance: Week 1: 4.7-10.5 mL/kg/min; Week 24: 1.1-55.9 mL/kg/min
Administration
IV Preparation
Reconstitute total amount to be infused in 250 mL NS (calculate total volume of galsulfase, remove that volume from a 250 mL bag of NS, add galsulfase to obatin 250 mL infusion soln).
Consider reducing infusion volume to 100 mL for pt <20 kg & susceptible to fluid overload (no need to remove NS from bag to accomodate galsulfase volme)
Use immediately (or within a 48-hr time from dilution to end of administration if refrigerated at 2-8 C)
IV Administration
Infused over no less than 4 hr using infusion pump (reduce infusion rate if <250 mL used to maintain at least 4 hr infusion time)
Initial rate 6 mL/hr, may be incr to 80 mL/hr if well-tolerated
Infusion time may be incr up to 20 hr if infusion reactions occur
Storage
2-8 C
Do not freeze or overshake
