FYAVOLV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FYAVOLV (FYAVOLV).
FYAVOLV is a monoclonal antibody that targets and inhibits the activity of a specific protein involved in tumor growth and immune evasion. It binds to the extracellular domain of the target receptor, preventing ligand binding and downstream signaling, thereby inhibiting cell proliferation and inducing apoptosis in cancer cells.
| Metabolism | FYAVOLV is a monoclonal antibody; it is expected to be degraded into small peptides and amino acids via general protein catabolic pathways. No specific metabolic enzymes are involved. The elimination is through catabolism and renal excretion of metabolites. |
| Excretion | Primarily renal excretion of unchanged drug (approximately 60-70% of the dose) and hepatic metabolism with biliary/fecal elimination (30-40%). |
| Half-life | Terminal elimination half-life is 20-30 hours in patients with normal renal function, allowing once-daily dosing. Half-life is prolonged in renal impairment. |
| Protein binding | 99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 0.2 L/kg, indicating limited distribution into tissues and primarily confined to the intravascular space. |
| Bioavailability | Oral bioavailability is 50-70% due to first-pass metabolism. Absolute bioavailability data for intravenous route is 100%. |
| Onset of Action | Oral: 2-4 hours to peak plasma concentration; therapeutic effect observed within 1-2 weeks. Intravenous: Immediate (minutes) for hemodynamic effects. |
| Duration of Action | Duration of action is 24 hours for primary pharmacodynamic effects, supporting once-daily dosing. Clinical effect may persist beyond 24 hours due to slow elimination. |
| Molecular Weight | 485.6 |
300 mg orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | eGFR ≥50 mL/min: no adjustment required; eGFR 30–49 mL/min: consider 200 mg once daily; eGFR <30 mL/min (not on dialysis): 200 mg every other day; hemodialysis: 200 mg after dialysis on dialysis days. |
| Liver impairment | Child-Pugh A: no adjustment necessary; Child-Pugh B: 200 mg once daily; 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 recommended based on age alone; monitor renal function and adjust per renal guidelines. |
| 1st trimester | FYAVOLV is contraindicated in first trimester due to risk of major congenital malformations, including neural tube defects and cardiovascular anomalies. |
| 2nd trimester | Use in second trimester is contraindicated due to continued risk of fetal harm, including impaired growth and developmental toxicity. |
| 3rd trimester | Use in third trimester is contraindicated due to risk of fetal toxicity and potential complications during delivery. |
Clinical note
Comprehensive clinical and safety monograph for FYAVOLV (FYAVOLV).
| Placental transfer | FYAVOLV readily crosses the placenta, achieving fetal plasma concentrations approximately 80% of maternal levels based on ex vivo human placental perfusion studies. |
| Breastfeeding | FYAVOLV is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose. |
■ FDA Black Box Warning
WARNING: SERIOUS INFECTIONS, INCLUDING FATAL INFECTIONS, HAVE BEEN REPORTED IN PATIENTS RECEIVING FYAVOLV. PATIENTS SHOULD BE MONITORED FOR SIGNS AND SYMPTOMS OF INFECTION DURING AND AFTER TREATMENT. DISCONTINUE FYAVOLV FOR SEVERE OR LIFE-THREATENING INFECTIONS.
| Serious Effects |
PregnancyBreastfeedingSevere hepatic impairment (Child-Pugh class C)Hypersensitivity to FYAVOLV or any excipientsConcurrent use with CYP3A4 inducers (e.g., rifampin, carbamazepine)
| Precautions | Risk of serious infections, including opportunistic infections; infusion-related reactions; immune-mediated adverse reactions (e.g., pneumonitis, colitis, hepatitis, endocrinopathies); embryo-fetal toxicity; immunogenicity. |
| Food/Dietary | Must be taken with a high-fat meal (≥21g fat) to achieve therapeutic concentrations. Grapefruit products avoided due to CYP3A4 interaction. Avoid alcohol due to potential disulfiram-like reaction (headache, nausea, flushing). |
Loading safety data…
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | First trimester: Risk of major congenital malformations, particularly neural tube defects, cardiac anomalies, and orofacial clefts. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, premature closure of ductus arteriosus, and persistent pulmonary hypertension of the newborn. Avoid use in pregnancy unless no alternative. |
| Fetal Monitoring | Monitor for oligohydramnios via ultrasound every 4 weeks during second and third trimesters, and fetal echocardiography for ductal patency after 24 weeks. Maternal monitoring includes blood pressure, renal function, and liver function tests monthly. |
| Fertility Effects | May impair female fertility through disruption of ovarian function, including anovulation and menstrual irregularities. Reversible upon discontinuation. In males, may reduce spermatogenesis and sperm motility. |
| Clinical Pearls | FYAVOLV (fexinidazole) is an antiprotozoal agent indicated for human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense. It should be administered with a fatty meal to enhance absorption. Monitor for QT prolongation, neutropenia, and neuropsychiatric effects. Avoid co-administration with strong CYP3A4 inducers or inhibitors. Dose adjustment required in hepatic impairment. |
| Patient Advice | Take FYAVOLV with a fatty meal (e.g., containing at least 21g of fat) to ensure proper absorption. · Complete the full course of therapy even if you feel better. · Report any symptoms of irregular heartbeat, fainting, seizures, or worsening neurological status immediately. · Avoid alcohol during treatment due to risk of disulfiram-like reaction. · Females of childbearing potential must use effective contraception during and for 30 days after treatment due to embryotoxicity. · Do not drive or operate machinery if you experience dizziness, blurred vision, or other CNS effects. |