FABRAZYME
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FABRAZYME (FABRAZYME).
Fabrazyme (agalsidase beta) is a recombinant human alpha-galactosidase A enzyme that hydrolyzes globotriaosylceramide (Gb3) and other glycosphingolipids with terminal alpha-galactosyl residues, thereby reducing accumulation of these substrates in tissues.
| Metabolism | Fabrazyme is a protein; metabolism is expected to involve catabolic pathways to small peptides and amino acids via proteolysis. |
| Excretion | Primarily eliminated via renal pathways; 55-65% of the administered dose is recovered in urine as unchanged drug, with less than 5% recovered in feces. |
| Half-life | Terminal elimination half-life ranges from 80 to 120 minutes (1.3-2 hours) in adults, which supports a bi-weekly intravenous dosing regimen. |
| Protein binding | Approximately 50% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.2-0.4 L/kg (16-30 L in a 70 kg adult), suggesting limited distribution into tissues; however, uptake into target organs (kidney, heart, endothelium) is mediated by mannose-6-phosphate receptors. |
| Bioavailability | Only administered intravenously; bioavailability is 100% by the IV route. |
| Onset of Action | Intravenous: Reduction in plasma globotriaosylceramide (GL-3) levels observed within 1-2 weeks following initiation of therapy. |
| Duration of Action | Duration of enzymatic activity in plasma is approximately 7-10 days, with sustained reduction in GL-3 accumulation in tissues over the 2-week dosing interval. |
1 mg/kg intravenously every 2 weeks infused over 4-6 hours.
| Dosage form | VIAL |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Same as adult: 1 mg/kg intravenously every 2 weeks. |
| Geriatric use | No specific dose adjustment; same as adult dosing based on body weight. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FABRAZYME (FABRAZYME).
| Breastfeeding | It is unknown whether agalsidase beta is excreted into human breast milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants, caution should be exercised when Fabrazyme is administered to a nursing woman. M/P ratio not available. Consider the importance of the drug to the mother and the potential risk to the infant. |
| Teratogenic Risk | No evidence of teratogenicity in animal studies. Limited human data; Fabrazyme (agalsidase beta) is a recombinant enzyme used for Fabry disease. In pregnant women, no adequate and well-controlled studies exist. Based on postmarketing reports, no pattern of congenital anomalies has emerged. The potential benefit to the mother should be weighed against the unknown fetal risk. Generally, use during pregnancy only if clearly needed. No trimester-specific risks have been identified. |
■ FDA Black Box Warning
None
| Serious Effects |
["History of severe hypersensitivity reaction (e.g., anaphylaxis) to agalsidase beta or any component of the formulation"]
| Precautions | ["Infusion-associated reactions (IARs) including severe hypersensitivity reactions, anaphylaxis, and immune complex deposition","Risk of severe allergic reactions, including anaphylaxis, especially in patients with anti-Fabrazyme antibodies","Possible development of anti-drug antibodies (ADA) that may reduce efficacy or cause hypersensitivity","Monitor for signs of infusion reactions; premedication with antihistamines and corticosteroids may be indicated"] |
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| Fetal Monitoring | Monitor pregnant women for infusion reactions (including rigors, fever, dyspnea, hypotension) which may be severe. Assess renal function, cardiac status, and pain levels as per Fabry disease management. Fetal monitoring should include routine prenatal assessments. No specific additional monitoring mandated. |
| Fertility Effects | Effects on fertility have not been studied in humans. In animal studies, no adverse effects on male or female fertility were observed at doses up to 10 mg/kg (approximately 3 times the human dose based on body surface area). It is unknown if Fabrazyme impacts human fertility. |