Renesis

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

Roxadustat is an orally bioavailable, hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), with potential anti-anemic activity. Upon administration, roxadustat binds to and inhibits HIF-PH, an enzyme responsible for the degradation of transcription factors in the HIF family under normal oxygen conditions. This prevents HIF breakdown and promotes HIF activity. Increased HIF activity leads to an increase in endogenous erythropoietin production, thereby enhancing erythropoiesis. It also reduces the expression of the peptide hormone hepcidin, improves iron availability, and boosts hemoglobin (Hb) levels. HIF regulates the expression of genes in response to reduced oxygen levels, including genes required for erythropoiesis and iron metabolism.

Administration of roxadustat has been shown to induce coordinated erythropoiesis, increasing red blood cell count while maintaining plasma erythropoietin levels within or near normal physiologic range, in multiple subpopulations of CKD patients, including in the presence of infammation, and without a need for supplemental intravenous iron.

Roxadustat reversibly binds to and potently inhibits hypoxia-inducible factor (HIF) prolyl hydroxylase enzymes, reducing HIF-α breakdown and promoting HIF transcriptional activity. Activation of the HIF pathway in this manner results in the induction of target genes involved in erythropoiesis, such as those for EPO, EPO receptor, proteins promoting iron absorption, iron transport and haem synthesis. Roxadustat dose-dependently increased haemoglobin (Hb) levels, signifcantly reduced hepcidin levels and transiently increased endogenous EPO levels within or near physiological range in patients with anemia of CKD who were not dialysis dependent. Roxadustat reduced the dysregulation of iron metabolism associated with CKD by increasing serum transferrin, intestinal iron absorption and the release of stored iron in a dose-dependent manner in patients with anemia associated with dialysis dependent or dialysis-independent CKD. Cholesterol levels were also signifcantly reduced from baseline with roxadustat, regardless of the use of statins or other lipid-lowering agents.

Roxadustat in combination with other medications may have drug-drug interaction.

Roxadustat with Phosphate binders and other products containing multivalent cation (EXCEPT) lanthanum carbonate:

• Risk: decreased roxadustat AUC by 67% and 46% and Cmax by 66% and 52%
• Recommendation: Roxadustat should be taken at least 1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations.

Roxadustat with gemfbrozil (CYP2C8 and OATP1B1inhibitor) or probenecid (UGT and OAT1/OAT3 inhibitor)

• Risk: increased roxadustat AUC by 2.3- fold and Cmax by 1.4-fold
• Recommendation: Adjust the dose of roxadustat following dose adjustment rules based on Hb monitoring.

Roxadustat with OATP1B1 or BCRP Substrates (simvastatin, rosuvastatin & atorvastatin)

• Risk: AUC and Cmax increased
• Recommendation: Adjust the dose of roxadustat following dose adjustment rules based on Hb monitoring.

The common adverse reactions associated with roxadustat are hypertension, vascular access thrombosis, diarrhoea, peripheral oedema, hyperkalaemia and nausea.

Do not administered to women that may be pregnant or pregnant. Roxadustat is contraindicated during breast-feeding.

Roxadustat tablets should be used in caution. It may initiate few thrombotic vascular events (TVEs) particularly in patients with pre-existing risk factors for TVE, including obesity and prior history of TVEs. Roxadustat should be used with caution in patients with a history of seizures. Roxadustat should not be administered if the patient has serious signs and symptoms of an infection. Roxadustat should not be administered if the patient has liver disorder. Roxadustat should not be initiated in pregnant women.

Children: Roxadustat is not indicated in children.

liver dysfunction patients: Roxadustat is not recommended for use in patients with severe hepatic impairment.

Drugs for Haemolytic Hypoplastic & Renal Anemia

Symptoms: When this drug was administered 5 mg/kg (510 mg) to a single healthy adult, increased heart rate transient have been reported. Hemoglobin concentration by overdosage of this drug is likely to increase more than necessary.

Treatment: Appropriate measures of dose reduction or interruption, etc. of this drug. This drug is not removed by dialysis.

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