Oroxat

Approved Indications:

• Anemia associated with Chronic Kidney Disease (CKD):
• In adult patients with CKD on dialysis.
• In adult patients with CKD not on dialysis.

Clinically Accepted Off-label Uses:

• Anemia in cancer patients (under research and limited data).
• Anemia of inflammation or other hypoxia-related anemia (investigational in some regions).

Route: Oral (tablet form).

Dosage in Adults (CKD-related Anemia):

• Non-dialysis patients:
  Starting dose: 70–100 mg orally three times a week (TIW), based on body weight.
• <60 kg: 70 mg TIW
• ≥60 kg: 100 mg TIW
• Dialysis-dependent patients:
  Same starting dose as above. Dose adjustments are based on hemoglobin response.

Pediatrics:

• Not recommended due to insufficient data.

Elderly:

• No specific dose adjustment; monitor hemoglobin closely.

Renal Impairment:

• No adjustment required as drug is used for CKD-related anemia.

Hepatic Impairment:

• Use with caution in moderate to severe hepatic impairment; monitor liver function.

Administration Notes:

• Can be taken with or without food.
• Swallow whole; do not crush or chew.
• Adjust dose no more frequently than every 4 weeks based on hemoglobin levels.

Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI). It stabilizes HIF transcription factors by inhibiting prolyl hydroxylase enzymes that normally mark HIF for degradation in normoxic conditions. This leads to increased endogenous erythropoietin production, improved iron metabolism, and enhanced red blood cell production. The drug mimics a hypoxic response, thereby stimulating erythropoiesis without requiring external erythropoietin.

• Absorption: Oral bioavailability is moderate; peak plasma concentration reached in ~2 hours post-dose.
• Distribution: Volume of distribution ~50–60 L; ~99% protein-bound (mostly albumin).
• Metabolism: Primarily metabolized in the liver by non-CYP pathways and minor involvement of CYP2C8 and CYP2C9.
• Half-life: Terminal elimination half-life is ~12–14 hours.
• Excretion: Mainly excreted in feces (~60%), remainder in urine (~20%).

• Pregnancy:
  Not assigned by FDA. Animal studies showed adverse fetal effects. Use only if benefits outweigh risks.
  Avoid during pregnancy unless no alternatives are available.
• Lactation:
  Unknown if excreted in human milk. Caution advised. Consider risk-benefit before prescribing to breastfeeding mothers.
• Recommendation: Avoid use during pregnancy and lactation unless absolutely necessary.

• Primary Class: Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI)
• Subclass: Oral erythropoiesis-stimulating agent (ESA) alternative

• Known hypersensitivity to Roxadustat or any of its components
• Uncontrolled hypertension
• Active malignancy (use with caution due to theoretical risk of tumor progression)
• History of thromboembolic disease (use cautiously)

• Thromboembolic Events: Increased risk; monitor patients for signs.
• Hypertension: May elevate blood pressure; manage appropriately.
• Hepatic Impairment: Use cautiously; limited data in severe impairment.
• Iron Monitoring: Regular assessment of iron status necessary.
• Tumor Progression Risk: Theoretical risk due to HIF pathway activation—use cautiously in cancer patients.
• Retinopathy & Seizures (rare): Monitor neurological and ophthalmic status.

Common (≥1%):

• Hypertension
• Headache
• Nausea
• Diarrhea
• Fatigue
• Hyperkalemia
• Peripheral edema

Less Common or Serious:

• Thromboembolic events (DVT, pulmonary embolism)
• Increased ALT/AST
• Seizures (rare)
• Retinopathy
• Hypersensitivity reactions

Severity: Most adverse effects are mild to moderate and dose-dependent. Serious effects (e.g., thrombosis) require immediate discontinuation.

• CYP450 involvement: Roxadustat is a weak substrate of CYP2C8, CYP2C9, and UGT enzymes.
• Major Interactions:
• CYP2C8 inhibitors (e.g., gemfibrozil): May increase Roxadustat levels—monitor closely.
• CYP2C8 inducers (e.g., rifampin): May reduce efficacy.
• Iron supplements/IV iron: May reduce drug effectiveness if iron is overloaded; monitor ferritin and TSAT.
• Food/Alcohol: No significant food interactions. Alcohol not contraindicated but should be limited in hepatic disease.

• EMA & FDA Approval Status:
• Approved in China, Japan, and the EU for CKD-related anemia.
• Not FDA approved in the US as of 2025 due to pending cardiovascular safety data.
• Updated Guidelines:
• KDIGO guidelines note HIF-PHI agents (including Roxadustat) as alternatives to ESAs in specific patients with CKD-related anemia, especially non-dialysis patients intolerant to injectable ESAs.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity/Light: Store in original container; protect from moisture and light.
• Handling: Do not freeze. Do not crush or chew tablets.
• Special Precautions: Keep out of reach of children. No refrigeration needed.