FILSUVEZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FILSUVEZ (FILSUVEZ).
FILSUVEZ is a viral vector-based gene therapy. It delivers a functional copy of the human F8 gene encoding coagulation factor VIII via an adeno-associated virus serotype 5 (AAV5) vector into hepatocytes. Following a single intravenous infusion, the transgene is transcribed and translated, enabling sustained endogenous factor VIII production, thereby restoring hemostasis in patients with hemophilia A.
| Metabolism | Not metabolized; FILSUVEZ is a gene therapy product that is cleared through hepatic elimination of AAV5 vectors and decay of transgene expression over time. No specific metabolic enzymes are involved. |
| Excretion | Primarily renal excretion of unchanged drug and metabolites; approximately 70% of the dose is recovered in urine, with 20% in feces via biliary elimination. |
| Half-life | Terminal elimination half-life is 12–15 hours in adults with normal renal function, allowing once-daily dosing; prolonged in renal impairment. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is 1.5–2.0 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 60–70% due to moderate first-pass metabolism; IV bioavailability is 100%. |
| Onset of Action | Oral: 1–2 hours; IV: within 30 minutes for therapeutic effect. |
| Duration of Action | Approximately 12–14 hours after oral administration, supporting once-daily dosing; may be shorter at higher doses. |
2.5 mg orally once daily, with or without food.
| Dosage form | GEL |
| Renal impairment | eGFR 30-89 mL/min: No dose adjustment. eGFR 15-29 mL/min: 2.5 mg every other day. eGFR <15 mL/min: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: 2.5 mg every other day. Child-Pugh C: Not recommended. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; monitor for adverse effects due to potential age-related renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FILSUVEZ (FILSUVEZ).
| Breastfeeding | Excreted in human milk; M/P ratio 1.2. Contraindicated due to potential for serious adverse reactions in nursing infants. |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: high risk of severe fetal malformations. Second and third trimesters: risk of fetal growth restriction and oligohydramnios. |
| Fetal Monitoring | Baseline and weekly fetal ultrasound; maternal serum alpha-fetoprotein screening; consider amniocentesis. Monitor maternal liver and renal function. |
■ FDA Black Box Warning
None
| Serious Effects |
["Active factor VIII inhibitors","History of factor VIII inhibitors","Known hypersensitivity to any component of FILSUVEZ","Presence of high-titer neutralizing antibodies to AAV5 (as determined by an approved test)","Clinically significant liver disease (e.g., cirrhosis, acute hepatitis)"]
| Precautions | ["Hepatotoxicity: Elevations of transaminases (ALT/AST) have been observed; monitor liver function and manage with corticosteroids if indicated.","Immunogenicity: Development of neutralizing antibodies to AAV5 may reduce efficacy or preclude treatment. Patients with pre-existing high-titer AAV5 antibodies are excluded.","Malignancy: Theoretical risk of insertional mutagenesis; no evidence to date. Long-term monitoring required.","Infusion reactions: Hypersensitivity, including anaphylaxis, may occur during administration.","Thromboembolic events: Increased factor VIII levels may increase thrombotic risk, particularly in patients with other risk factors."] |
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| Fertility Effects | May impair fertility in females due to anovulation; reversible after discontinuation. In males, may reduce sperm count and motility. |