ClinCalc Pro
Menu
Calculators Drugs Pathways AI Dx Donate Get the App
HIF-PHI — Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (Anaemia of CKD) Pregnancy: Contraindicated — teratogenic in animal studies. Effective contraception required during treatment and for 1 week after stopping.

Roxadustat

Brand names: Evrenzo

Adult dose

Dose: 70 mg three times weekly (non-dialysis, starting dose). Dialysis: 100 mg three times weekly. Titrate by 40–50 mg increments every 4 weeks based on haemoglobin response
Route: Oral
Frequency: Three times weekly (not on consecutive days — e.g. Mon/Wed/Fri)
Max: 3 mg/kg or 400 mg per dose (whichever is lower)
Take 1 hour before food or 2 hours after food (food reduces absorption). Target Hb: 10–12 g/dL for non-dialysis CKD; up to 12 g/dL for dialysis. Not for use in non-anaemia. Source: BNF 90; MHRA SPC Evrenzo; NICE TA812.

Paediatric dose

Dose: Not licensed under 18 years N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Not licensed in paediatric CKD anaemia.

Dose adjustments

Renal

No dose adjustment required for renal impairment — specifically designed for CKD patients across all eGFR ranges including dialysis. Dose titrated by Hb response, not eGFR.

Hepatic

Mild-moderate hepatic impairment: no dose adjustment. Severe (Child-Pugh C): avoid — significantly increased exposure. Monitor LFTs closely in hepatic impairment.

Paediatric weight-based calculator

Not licensed in paediatric CKD anaemia.

Clinical pearls

  • Novel mechanism — HIF pathway activation: PHD enzymes normally hydroxylate HIF-2α → ubiquitin-mediated degradation. Roxadustat inhibits PHD → HIF-2α accumulates → activates endogenous EPO gene transcription + increases iron absorption. Mimics high-altitude physiology. Different from exogenous EPO — no injection needed.
  • MHRA 2023 cardiovascular warning: OLYMPUS trial showed increased risk of MACE (MI, stroke, death) and VTE in non-dialysis CKD patients with high CV risk. MHRA recommends roxadustat should NOT be used as first-line in patients with high CV risk — weigh benefits vs risks carefully. Reserve for patients who cannot use ESAs or in whom IV iron is insufficient.
  • NICE TA812: recommended for dialysis-dependent CKD anaemia when ESA (e.g. darbepoetin) is not appropriate, or for non-dialysis CKD when iron therapy has been optimised and Hb still below target. NOT first-line.
  • Statin interaction — clinically important: roxadustat inhibits hepatic transporters (OATP1B1/3) and efflux pumps (BCRP), increasing statin plasma concentrations. Rosuvastatin and pravastatin most affected. Maximum statin dose reductions may be required. Screen statin prescriptions before initiating.
  • Take on empty stomach: food reduces bioavailability by 30–40%. Iron-containing phosphate binders are the most clinically important interaction — separate by at least 1 hour. Calcium-based binders: separate by 2 hours. Source: BNF 90; MHRA Drug Safety Update 2023; NICE TA812.

Contraindications

  • Uncontrolled hypertension
  • High cardiovascular risk with active ischaemic heart disease or heart failure (major MHRA warning — see pearls)
  • Pregnancy and breastfeeding (teratogenic)
  • Target Hb already ≥12 g/dL
  • Phenylketonuria (some formulations contain phenylalanine)

Side effects

  • Hypertension (most common — vasodilation of erythropoietin-mediated vessels, monitor BP carefully)
  • Thromboembolic events (DVT, PE, arterial thrombosis) — MHRA warning 2023
  • Major adverse cardiovascular events (MACE) — MHRA warning based on OLYMPUS trial data
  • Peripheral oedema
  • Hyperkalaemia
  • Nausea, vomiting, diarrhoea
  • Elevated transaminases
  • Seizures (rare — mechanism unclear)

Interactions

  • Phosphate binders (calcium-based, iron-based): reduce roxadustat absorption — take roxadustat 1 hour before or 2 hours after phosphate binders. Significant interaction with iron preparations
  • Statins (especially rosuvastatin, pravastatin): roxadustat inhibits OATP1B1/3 and BCRP — statin concentrations may increase. Reduce statin dose or avoid high-dose statins
  • Strong CYP2C8 inhibitors (gemfibrozil): increase roxadustat exposure — avoid
  • Probenecid: increases roxadustat — avoid

Monitoring

  • Haemoglobin every 2 weeks until stable, then monthly (target 10–12 g/dL)
  • Blood pressure (weekly for first month, then monthly)
  • Cardiovascular symptoms (chest pain, dyspnoea, leg swelling — VTE)
  • Liver function tests at baseline, monthly for 3 months, then every 3 months
  • Serum potassium (hyperkalaemia risk in CKD)
  • Iron studies (serum ferritin, TSAT) — iron deficiency limits response to HIF-PHI

Reference: BNFc; BNF 90; MHRA Drug Safety Update 2023 (cardiovascular risk); NICE TA812 (roxadustat for CKD anaemia); Chen et al. NEJM 2021 (OLYMPUS trial). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

Calculators
Pathways