Dosing and uses of Fabrazyme (agalsidase beta)
Adult dosage forms and strengths
powder for injection
- 5mg/vial
- 35mg/vial
Fabry Disease
1 mg/kg IV infusion q2Weeks
Infuse initial infusion over 4-6 hours; subsequent infusions may be administered at 3-5 mg/min
Pediatric dosage forms and strengths
powder for injection
- 5mg/vial
- 35mg/vial
Fabry Disease
<8 years: Safety & efficacy not established
≥8 years: As adult; 1 mg/kg IV infusion q2Weeks
Fabrazyme (agalsidase beta) adverse (side) effects
>10%
Infusion Reactions (50-55%)
- Decrease frequency with continued treatment
- Bradycardia, flushing, hypertension, hypotension, peripheral edema, tachycardia
- Chills, dizziness, fatigue, feeling hot or cold, headache, pain in extremity, paresthesia, pyrexia, somnolence
- Abdominal pain, diarrhea, nausea, vomiting
- Pruritus, Urticaria
- Myalgia
- Chest pain, dyspnea, nasal congestion, throat tightness
Upper respiratory tract infections (44%)
Chills (43%)
Headache (39%)
Pyrexia (39%)
Paresthesia (31%)
Fatigue (24%)
Dizziness (21%)
Edema peripheral (21%)
Cough (20%)
Pain in extremity (19%)
Lower respiratory tract infection (18%)
Back pain (16%)
Pain (16%)
Myalgia (14%)
Hypertension (14%)
Feeling cold (11%)
1-10%
Pruitus (10%)
Excoriation (9%)
Sinusitis (9%)
Sr creatinine increased (9%)
Tachycardia (9%)
Dyspnea (8%)
Respiratory tract congestion (8%)
Tinnitus (8%)
Anxiety (6%)
Burning sensation (6%)
Depression (6%)
Fall (6%)
Pharyngitis (6%)
Toothache (6%)
Wheezing (6%)
Chest discomfort (5%)
Fungal infection (5%)
Hot flash (5%)
Hypoacusis (5%)
Muscle spasms (5%)
Ventricular wall thickening (5%)
Viral infections (5%)
Confusion (4%)
Dry mouth (4%)
Localized infection (4%)
Thermal burn (4%)
Warnings
Contraindications
Hypersensitivity to product or components
Cautions
Moderate-to-severe HTN, renal impairment, febrile patients, patients with prior sensitivity to agalsidase products
Severe reactions occur may occur despite premedication; decrease infusion rate or temporarily discontinue infusion and/or administer additional antihistamines, antipyretics, and/or steroids to manage infusion reactions; in severe reactions may consider immediate discontinuation of infusion
Development of IgG antibodies reported within 3 months from the onset of therapy; some may also develop IgE antibodies
Premedicate with antipyretics 1 hr before infusion
Use caution in patients with cardiovascular diseases
Fabry Disease Registry has been created to monitor therapeutic responses and adverse effects; www.fabryregistry.com or 1-800-745-4447
Pregnancy and lactation
Pregnancy category: B
Lactation: Not known if distributed into breast milk, use 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 Fabrazyme (agalsidase beta)
Mechanism of action
Recombinant alpha-galactosidase A, an enzyme (deficient in Fabry disease) involved in the metabolism of glycosphingolipids (eg, GL-3); corrects abnormal glycosphingolipid metabolism resulting in reduced accumulation of glycosphingolipids and improvement of associated clinical manifestations; reduces GL-3 deposition in capillary endothelium
Pharmacokinetics
Half-Life: 86-151 min (children); 45-119 min (adults)
Onset: 10-20 wk
Vd: 247-1097 mL/kg; 81-570 mL/kg
Administration
IV Incompatibilities
Should not be infused in the same intravenous line with other products.
IV Preparation
Reconstitute 35 mg vial by injecting 7.2 mL of SWI & 5 mg vial by injecting 1.1 mL SWI to yield a 5 mg/mL clear, colorless solution
Visually inspect the reconstituted vials for particulate matter & discoloration
Do not use the reconstituted solution if there is particulate matter or if it is discolored
The reconstituted solution should be further diluted with NS to a final total volume of 50-500 mL based on dosage
Remove dose amount of NS from infusion bag & replace w/ drug solution
IV Administration
Reconstituted & diluted solns should be used immediately (drug contains no preservatives); however may be stored in fridge for up to 24 hr
Initial infusion rate
- Not to exceed 0.25 mg/min (15 mg/hr); may incr by 0.05-0.08 mg/min (3-5 mg/hr) for on each subsequent infusion
- <30 kg: not to exceed 0.25 mg/min
- >30 kg: infuse over at least 1.5 hr
Do not shake or agitate product
Do not use filter needles during the preparation of the infusion
Storage
Refrigerate
