VAFSEO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VAFSEO (VAFSEO).
VAFSEO (vadadustat) is a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor. It stabilizes HIF-α, leading to increased transcription of genes involved in erythropoiesis, including erythropoietin, enhancing red blood cell production.
| Metabolism | Primarily metabolized by CYP2C8 and UGT1A9; minor pathways include CYP3A4 and CYP2C9. |
| Excretion | Primarily fecal (approximately 81%) and renal (~17%) as unchanged drug and metabolites. |
| Half-life | Terminal half-life is approximately 20-30 hours, supporting once-daily dosing. |
| Protein binding | ~50% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent volume of distribution is approximately 1.5 L/kg, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 60-70% (not affected by food). |
| Onset of Action | Onset of action after oral administration is within 2-4 weeks, with maximum hemoglobin response by 8-12 weeks. |
| Duration of Action | Duration of action is sustained over 24 hours with once-daily dosing; therapeutic effect persists as long as treatment continues. |
Oral: 20 mg three times weekly for 24 weeks.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for any degree of renal impairment. |
| Liver impairment | No dosage adjustment required for mild to severe hepatic impairment (Child-Pugh A, B, or C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to limited data. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VAFSEO (VAFSEO).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or effects on milk production. The molecular weight (~340 Da) suggests potential excretion. Due to potential for serious adverse reactions (e.g., effects on erythropoiesis), breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose. M/P ratio: unknown. |
| Teratogenic Risk | Vafseo (vadadustat) is a hypoxia-inducible factor prolyl hydroxylase inhibitor. There are no adequate human data on teratogenic risk. In animal studies, vadadustat caused embryofetal toxicity (reduced fetal weight, skeletal variations) at exposures similar to human exposure at the maximum recommended human dose. Based on mechanism of action, potential risks include impaired implantation and fetal development. First trimester: unknown risk; second and third trimesters: potential fetal hypoxia from altered erythropoiesis. Vafseo should be avoided during pregnancy unless clearly needed. |
■ FDA Black Box Warning
Increased risk of thrombosis, including vascular access thrombosis, deep vein thrombosis, pulmonary embolism, and myocardial infarction. Not approved for use in patients with active malignancy due to potential for tumor progression.
| Serious Effects |
["Uncontrolled hypertension","Active malignancy","History of thrombotic events (relative)","Hypersensitivity to vadadustat or any component"]
| Precautions | ["Thrombotic events","Increased mortality in patients with cancer","Hypertension","Seizures","Gastric erosion and bleeding","Serious hepatotoxicity","Potential for tumor growth","Not for treatment of anemia due to other causes","Monitor hemoglobin levels"] |
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| Fetal Monitoring | Monitor hemoglobin weekly until stable, then monthly; assess iron stores (ferritin, transferrin saturation) monthly; monitor blood pressure regularly for hypertension; assess for thromboembolic events. In pregnancy, consider fetal ultrasound for growth and amniotic fluid volume if exposure occurs. |
| Fertility Effects | In animal studies, vadadustat did not impair fertility in male or female rats at exposures up to 6 times the human exposure. No human data on fertility effects. Based on mechanism, potential for altered erythropoiesis may impact ovarian or testicular function, but clinically significant effects are unlikely. |