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Galsulfase

Trade Names:
Naglazyme
- Solution for injection 1 mg/mL

Mechanism of Action

Pharmacology

Galsulfase is a glycoprotein that is intended to provide an exogenous enzyme that will be taken up into lyosome and increase the catabolism of glycosaminoglycans. This is most likely mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of galsulfase to specific mannose-6-phosphate receptors.

Pharmacokinetics

Absorption

C _max is about 1.5 mcg/mL and AUC is about 4.3 mcg/mL.

Distribution

Vd is about 69 mL/kg.

Elimination

Cl is about 3.7 mL/kg/min; t _½ is about 26 min.

Indications and Usage

Treatment of patients with mucopolysaccharidosis (MPS) VI.

Contraindications

Standard considerations.

Dosage and Administration

IV infusion 1 mg/kg once weekly.

General Advice

• For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
• Consider pretreatment with antihistamines with or without antipyretics 30 to 60 min prior to start of infusion.
• Galsulfase solution is clear to slightly opalescent and colorless to pale yellow. Do not use if solution is cloudy, discolored, or contains particulate matter.
• Dilute galsulfase in 0.9% sodium chloride injection to final volume of 250 mL. For patients weighing 20 kg or less who are susceptible to fluid volume overload, consider diluting galsulfase in 100 mL 0.9% sodium chloride injection.
• Administer by IV infusion over no less than 4 hr using infusion pump with PVC infusion set equipped with in-line, low protein-binding 0.2 mcm filter.
• Initial infusion rate for 250 mL volume should be 6 mL/hr for first hour then increase to 80 mL/hr, if tolerated for the remaining 3 hr. Initial infusion rate for 100 mL volume should be 2.5 mL/hr for first hour then increased to 32 mL/hr if tolerated. Infusion time can be extended for up to 20 hr if infusion reactions occur.
• To prepare infusion solution: determine number of vials to be diluted, rounding to nearest whole vial; remove vials from refrigerator and allow them to reach room temperature (do not heat or microwave vials; do not allow vials to remain at room temperature for longer than 24 hr before dilution); for 250 mL volume, withdraw and discard a volume of 0.9% sodium chloride injection equal to volume of galsulfase to be added (for 100 mL volume this is not necessary); slowly withdraw prescribed dose of galsulfase from vials using caution to avoid excessive agitation, then slowly add galsulfase solution to 0.9% sodium chloride injection, using care to avoid agitation; gently rotate infusion bag to ensure proper distribution of galsulfase.
• Agitation of galsulfase solution may denature galsulfase, rendering it biologically inactive. Do not agitate vials or diluted solutions nor use filter needles when preparing diluted infusion solution.
• Galsulfase contains no preservatives. Discard any unused solution. Do not save for future use.
• Do not infuse with other products in the infusion tubing.

Storage/Stability

Store vials in refrigerator (36° to 46°F). Do not freeze or shake. Diluted infusion solution must be used immediately but can be stored in refrigerator. Storage after dilution should not exceed 48 hr from time of preparation to completion of infusion.

Drug Interactions

None well documented.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension (11%).

CNS

Areflexia, malaise (11%); headache.

Dermatologic

Face edema (11%).

EENT

Ear pain (42%); conjunctivitis (21%); pharyngitis (16%); increased corneal opacification, nasal congestion (11%); otitis media.

GI

Abdominal pain (53%); gastroenteritis (11%); diarrhea; vomiting.

Musculoskeletal

Rigors (21%); arthralgia.

Respiratory

Dyspnea (21%); cough; upper respiratory infection.

Miscellaneous

Infusion reactions (including abdominal pain, angioneurotic edema, apnea, bronchospasm, chills/rigors, dyspnea, elevated BP, fever, headache, hypotension, joint pain, malaise, mild to moderate urticaria, nausea, rash, respiratory distress, retrosternal pain, urticaria, and, vomiting [55%]); pain (26%); chest pain (16%); umbilical hernia (11%); fever.

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy in children younger than 5 yr of age not established.

Acute febrile or respiratory illness

Consider delaying therapy.

Immunogenicity

IgG antigalsulfase antibodies developed in 98% of treated patients; appearing typically within 4 to 8 wk of treatment.

Infusion reactions

May occur despite pretreatment with antihistamines. Reactions generally abate with slowing or temporary interruption of infusion and administration of additional antihistamines, antipyretics, and, if necessary, corticosteroids. Discontinue infusion immediately if severe reactions occur.

Sleep apnea

Common in MPS VI patients; antihistamine pretreatment may increase risk of apneic episodes. Evaluate airway patency prior to initiation of treatment. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments available during infusion if an infusion reaction, or extreme drowsiness/sleep induced by antihistamine use, occurs.

Overdosage

Symptoms

No experience.

Patient Information

• Explain name, action, dosing regimen, and potential side effects of drug.
• Advise patient or caregiver that medication will be prepared and administered by a health care provider in a health care setting.
• Advise patient or caregiver that reactions during infusion of galsulfase occur commonly and that medications may be given before the infusion in an effort to prevent or reduce the severity of these reactions.
• Advise patient or caregiver that a surveillance program has been established to better understand the variability and progression of the disease and to monitor and evaluate the long-term treatment effects of galsulfase, including the effect of galsulfase on pregnant women and their children, and to determine if the medication is excreted in breast milk. Encourage patient to participate and advise them that their participation is voluntary and may involve long-term follow-up.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breastfeeding.
• Instruct patient not to take any prescription or OTC medications, dietary supplements, or herbal preparations unless advised by health care provider.
• Remind patient or caregiver that therapy is administered once a week and to keep appointments.