Indications

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

Description

Roxatat is a first-in-class, orally administered HIF-PH (Hypoxia-Inducible Factor Prolyl Hydroxylase) inhibitor that stimulates erythropoiesis by increasing the body's natural production of erythropoietin (EPO). It also improves iron regulation and counteracts the inflammation-related suppression of hemoglobin synthesis and red blood cell production by reducing hepcidin levels.

Pharmacology

Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) with anti-anemic properties.

After administration, roxadustat inhibits the HIF-PH enzyme, which normally degrades HIF transcription factors under normal oxygen conditions. By preventing HIF degradation, roxadustat enhances HIF activity, leading to:

Increased endogenous erythropoietin (EPO) production
Enhanced erythropoiesis (red blood cell production)
Reduced hepcidin levels
Improved iron availability
Increased hemoglobin (Hb) levels

HIF regulates genes involved in response to low oxygen levels, including genes responsible for erythropoiesis and iron metabolism.

Clinical studies have shown that roxadustat promotes coordinated erythropoiesis, increases red blood cell counts, and maintains plasma erythropoietin concentrations within or close to the normal physiological range, even in CKD patients with inflammation and without the need for supplemental intravenous iron.

Roxadustat reversibly inhibits HIF prolyl hydroxylase enzymes, thereby reducing HIF-α degradation and promoting HIF-mediated gene transcription. This activates genes involved in:

Erythropoietin (EPO) production
EPO receptor expression
Iron absorption
Iron transport
Heme synthesis

In patients with CKD-related anemia, roxadustat:

Increases hemoglobin levels in a dose-dependent manner
Significantly reduces hepcidin levels
Temporarily increases endogenous EPO levels within or near physiological ranges
Improves iron metabolism
Increases serum transferrin levels
Enhances intestinal iron absorption
Promotes release of stored iron

Roxadustat has also been shown to significantly reduce cholesterol levels, regardless of concomitant use of statins or other lipid-lowering medications.

Dosage and Administration

Roxadustat should be taken orally three times weekly, ensuring that doses are not taken on consecutive days.

Treatment should be individualized to maintain target hemoglobin levels of 10–12 g/dL.

Patients Not Receiving Erythropoiesis-Stimulating Agents (ESA)

Adults:

Usual starting dose: 50 mg three times weekly

Recommended initial dose based on body weight:

Body weight less than 100 kg: 70 mg three times weekly
Body weight 100 kg or more: 100 mg three times weekly

Patients Switching from ESA Therapy

Adults:

Starting dose: 70 mg or 100 mg three times weekly

Subsequent dose adjustments should be based on clinical response and patient condition.

Dose Adjustment

When dose modification is required, doses should be adjusted according to established dose increase/decrease schedules.

After a dose adjustment:

Maintain the new dose for 2-4 weeks.
If hemoglobin rises rapidly (>2.0 g/dL within 4 weeks), reduce the dose or temporarily discontinue treatment immediately.

Stepwise Dose Adjustment Sequence

Available tablet strengths:

20 mg → 40 mg → 50 mg → 70 mg → 100 mg → 150 mg → 200 mg → 250 mg → 300 mg → 400 mg (for dialysis patients only)

Missed Dose

If a patient misses a dose:

Take it immediately if the next scheduled dose is 24 hours or more away.
If less than 24 hours remain before the next scheduled dose, skip the missed dose.
Do not take two doses on the same day.

Method of Administration

Roxadustat tablets may be taken:

With food
Without food