Roxadustat
Roxadustat is an orally active hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI) that raises endogenous erythropoietin and improves iron handling. Approved for CKD anaemia in China, Europe, Japan and elsewhere (FDA rejected in 2021 over safety), it is an attractive oral doping agent and is prohibited by WADA at all times.
01 Overview
Roxadustat inhibits the prolyl hydroxylase enzymes that normally tag HIF-alpha for degradation. By stabilising HIF, it mimics the body's response to hypoxia, increasing transcription of erythropoietin and iron-transport genes, thereby raising red cell production from an oral tablet rather than an injection.\n\nIts oral route and reliance on endogenous EPO make it appealing to endurance athletes; WADA lists HIF activating agents (including roxadustat) as prohibited, and detection assays exist. Regulatory review flagged concerns about thrombosis and, in some analyses, cardiovascular and mortality signals — the FDA declined approval in 2021 pending further data, while other regulators approved it with monitoring.
02 Mechanism
Inhibits HIF prolyl-4-hydroxylase, preventing degradation of HIF-alpha; stabilised HIF drives transcription of erythropoietin and genes improving iron absorption and mobilisation, increasing erythropoiesis.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| CKD anaemia (medical) | 70–150 mg | Oral | Three times weekly; weight-based, titrated to haemoglobin |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Increased endogenous EPO and haemoglobinRaises the body's own erythropoietin and improves iron utilisation, correcting anaemia orally. | Hb +1-2 g/dL | Clinical | |
| Improved iron availabilityReduces hepcidin and enhances iron absorption/mobilisation, supporting erythropoiesis without IV iron in some patients. | Lower hepcidin | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Thrombosis / cardiovascular eventsTrials and pooled analyses raised concern about thromboembolism and cardiovascular events; a key reason for the 2021 FDA rejection. | Severe | Signal in trials | Clinical | |
| Hyperkalaemia and hypertensionElevated potassium and blood pressure reported in trials. | Moderate | Common in CKD | Clinical |