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. |
| Molecular Weight | 362.35 |
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 | Avoid due to risk of fetal hypoxia and potential teratogenicity from hypoxia-inducible factor (HIF) stabilization. |
| 2nd trimester | Avoid; may reduce placental perfusion and fetal oxygen delivery. |
| 3rd trimester | Avoid; risk of fetal bradycardia and maternal hypotension. |
Clinical note
Comprehensive clinical and safety monograph for VAFSEO (VAFSEO).
| Placental transfer | Crosses placenta in animal studies; limited human data suggest transfer. |
| Breastfeeding | Excreted in human milk in low amounts; due to limited safety data and potential for serious adverse reactions in nursing infants, discontinue nursing or discontinue drug. |
| Lactation Rating |
■ 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 hypertensionKnown hypersensitivity to Vafseo or excipients
| 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 |
| Food/Dietary | No significant food interactions. May be taken with or without food. Avoid grapefruit products as they may increase drug levels (moderate CYP3A4 interaction). |
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| 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. |
| 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. |
| Clinical Pearls | VAFSEO (vadadustat) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) for anemia due to chronic kidney disease (CKD). Monitor hemoglobin every 2 weeks during dose titration; target Hb ≤11 g/dL to reduce thrombotic risk. Avoid in patients with active malignancy due to potential tumor growth promotion. Drug interactions: reduce dose of VAFSEO when co-administered with strong CYP2C8 inhibitors (e.g., gemfibrozil); avoid with rifampin. Do not use erythropoiesis-stimulating agents concurrently. Assess iron stores and replete iron as needed. |
| Patient Advice | Take VAFSEO exactly as prescribed, usually once daily with or without food. · Do not take VAFSEO if you have active cancer or are being treated for cancer. · Report signs of blood clots (e.g., leg swelling, chest pain, sudden shortness of breath) immediately. · Do not use other anemia medications (e.g., epoetin alfa) while on VAFSEO unless told by your doctor. · You will need regular blood tests to monitor hemoglobin and iron levels. · Take iron supplements if prescribed by your doctor; do not take additional iron without consulting your healthcare provider. · Inform all healthcare providers that you are taking VAFSEO. |