Roxadustat is indicated for the treatment of adult patients with symptomatic anemia associated with chronic kidney disease (CKD).

Roxadustat is a first-in-class, orally active hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor. It stimulates erythropoiesis by increasing endogenous erythropoietin (EPO) production, improving iron utilization, and reducing the inhibitory effects of inflammation on hemoglobin synthesis through downregulation of hepcidin.

Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) with anti-anemic properties. It inhibits HIF-prolyl hydroxylase enzymes, preventing degradation of hypoxia-inducible factor (HIF) transcription factors under normal oxygen conditions. This stabilizes HIF and enhances its activity.

Increased HIF activity stimulates endogenous erythropoietin production, improves iron metabolism, reduces hepcidin expression, and increases hemoglobin levels. HIF also regulates genes involved in erythropoiesis and iron homeostasis.

Roxadustat promotes coordinated red blood cell production while keeping plasma EPO levels within or near physiological range, even in CKD patients with inflammation, without requiring intravenous iron supplementation.

It also enhances iron availability by increasing intestinal absorption, transferrin production, and mobilization of stored iron. Additionally, it reduces serum cholesterol levels regardless of statin use.

The appropriate dose of roxadustat must be taken orally three times per week and not on consecutive days. The dose should be individualized to achieve and maintain target Hb levels of 10 to 12 g/dL as described below:

Patients not on erythropoiesis-stimulating agent treatment: For adults, the usual starting dose is 50 mg three times weekly. The recommended starting dose of roxadustat is 70 mg three times per week in patients weighing less than 100 kg and 100 mg three times per week in patients weighing 100 kg and over.

Patients switching from erythropoiesis-stimulating agents: For adults, the usual starting dose is 70 or 100 mg three times weekly. The dosage thereafter should be adjusted according to the patient's condition.

Dose adjustment: When dose adjustments are required, increase or decrease the dose according to the "Dose increase/decrease table" and "stepwise Dose adjustment sequence" below. Once adjusted, maintain the dose level for ≥4 weeks. If the hemoglobin concentration increases rapidly (>2.0 g/dL) within 4 weeks of a dose increase, decrease the dose or suspend the treatment immediately.

The stepwise dose adjustments up or down should follow the sequence of the available doses: 20 mg – 40 mg – 50 mg – 70 mg – 100 mg – 150 mg – 200 mg – 250 mg – 300 mg – 400 mg (only for CKD patients on dialysis).

Missed dose: When there is ≥24-hour interval until the next scheduled dosing time, take the missed dose immediately and follow the prescribed schedule for subsequent doses. If there is <24 hours until the next scheduled dosing time, skip the missed dose and take the next dose as scheduled. Do not take 2 doses on the same day.

Method of administration: Roxadustat tablets are to be taken orally with or without food.

Roxadustat may interact with other concomitantly used medicines.

Roxadustat with phosphate binders and other products containing multivalent cations (except lanthanum carbonate):

• Risk: Reduced roxadustat exposure (AUC decreased by ~67% and 46%, Cmax decreased by ~66% and 52%).
• Recommendation: Roxadustat should be taken at least 1 hour after phosphate binders or other medicinal products/supplements containing multivalent cations.

Roxadustat with gemfibrozil (CYP2C8 and OATP1B1 inhibitor) or probenecid (UGT and OAT1/OAT3 inhibitor):

• Risk: Increased roxadustat exposure (AUC increased ~2.3-fold, Cmax ~1.4-fold).
• Recommendation: Dose adjustment of roxadustat should be done based on hemoglobin monitoring.

Roxadustat with OATP1B1 or BCRP substrates (e.g., simvastatin, rosuvastatin, atorvastatin):

• Risk: Increased plasma levels (AUC and Cmax).
• Recommendation: Adjust roxadustat dose according to hemoglobin response monitoring.

Common adverse effects include hypertension, vascular access thrombosis, diarrhea, peripheral edema, hyperkalemia, and nausea.

Roxadustat should not be used in pregnant women or those who may become pregnant. It is contraindicated during breastfeeding.

Use with caution as Roxadustat may increase the risk of thrombotic vascular events, especially in patients with obesity or previous history of thrombosis. It should be used carefully in patients with seizure history. It should not be used in active serious infections or liver disorders. It is not recommended to initiate treatment during pregnancy.

Children: Not indicated in pediatric patients.
Hepatic impairment: Not recommended in severe liver impairment.

Overdose may cause increased heart rate and excessive rise in hemoglobin levels. Management includes dose reduction or temporary discontinuation. The drug is not removed by dialysis.

Drugs for haemolytic, hypoplastic & renal anemia

Store below 30°C in a cool, dry place. Protect from light and moisture. Keep out of reach of children.