Ckemia 2

_NAME_ is indicated for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least four months. _NAME_ is not indicated for use: As a substitute for red blood cell transfusions in patients who require immediate correction of anemia. For treatment of anemia of chronic kidney disease in patients who are not on dialysis.

_NAME_ is available in 1,2,4,6 and 8-mg tablet formulations administered orally once daily, with or without food.

Adults Not Being Treated with an Erythropoiesis-Stimulating Agent (ESA): Pre-Treatment Hemoglobin Level less than 9 g/dL: 4 mg orally once daily Pre-Treatment Hemoglobin Level 9 to 10 g/dL: 2 mg orally once daily Pre-Treatment Hemoglobin Level greater than 10 g/dL: 1 mg orally once daily Dosing based on adults being switched from an ESA: Dose of _NAME_: 4 mg orally once daily Epoetin alfa intravenous less than or equal to 2,000 units/week Darbepoetin alfa subcutaneous/intravenous 20 to 30 mcg/4 weeks Methoxy PEG-epoetin beta subcutaneous/intravenous 30 to 40 mcg/month Dose of _NAME_: 6 mg orally once daily Epoetin alfa intravenous greater than 2,000 to less than 10,000 units/week Darbepoetin alfa subcutaneous/intravenous greater than 30 to 150 mcg/4 weeks Methoxy PEG-epoetin beta subcutaneous/intravenous greater than 40 to 180 mcg/month Dose of _NAME_: 8 mg orally once daily Epoetin alfa intravenous greater than 2,000 to less than 10,000 units/week Darbepoetin alfa subcutaneous/intravenous greater than 150 to 300 mcg/4 weeks Methoxy PEG-epoetin beta subcutaneous/intravenous greater than 180 to 360 mcg/month Dose of _NAME_: 12 mg orally once daily Epoetin alfa intravenous greater than or equal to 20,000 units/week Darbepoetin alfa subcutaneous/intravenous greater than 300 mcg/4 weeks Methoxy PEG-epoetin beta subcutaneous/intravenous greater than 360 mcg/month Maximum dose: 24 mg orally once daily

Not recommended for children.

Steady-state exposure of _NAME_ is similar in patients with normal renal function and those with varying degrees of renal impairment Hemodialysis or peritoneal dialysis _NAME_ exposure not significantly impacted Systemic exposure of _NAME_ metabolites was higher in patients with Stage 3-5 CKD than in those with normal renal function. Exposures of metabolites were higher on non-dialysis days than on dialysis days.

Receiving a strong CYP2C8 inhibitor such as gemfibrozil. With uncontrolled hypertension.

-NAME_ is a reversible inhibitor of the hypoxia-inducible factors (HIFs) polyhomeotic-like proteins 1 to 3 (IC50 in the low-nanomoles range), a set of enzymes that degrade HIFs in normal oxygen conditions. HIF inhibition results in the stabilization and nuclear accumulation of the HIF 1α and 2α transcription factors, leading to increased transcription of the HIF-responsive genes, including that encoding erythropoietin. -NAME_increases endogenous erythropoietin in a dose-dependent manner in 6 to 8 hours after administration. With repeated doses, the peak increase in reticulocyte count occurs in 7 to 15 days, with subsequent increases in red blood cell production. New hemoglobin steady-state levels are reached in several weeks after initial administration (∼4 weeks in patients using erythropoiesis-stimulating agents [ESAs] and ∼16 to 20 weeks in patients not using ESAs).

Risk of hospitalization due to heart failure High blood pressure Damage to the lining of the stomach, the tube that connects the mouth and stomach (esophagus), and intestines (gastrointestinal erosion).

Not recommended in pregnancy. This drug resulted in fetal adverse outcomes in animal study.

CYP2C8 Inhibitors: Concomitant administration of strong CYP2C8 inhibitors (e.g., gemfibrozil) with _NAME_ is contraindicated due to a marked increase in _NAME_ exposure. CYP2C8 Inducers: CYP2C8 inducers (e.g., rifampin) may decrease _NAME_ exposure, which may result in loss of efficacy.