RETACRIT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RETACRIT (RETACRIT).
RETACRIT (epoetin alfa-epbx) is a recombinant human erythropoietin that stimulates erythropoiesis by binding to and activating the erythropoietin receptor on erythroid progenitor cells, promoting their survival, proliferation, and differentiation into mature red blood cells.
| Metabolism | Epoetin alfa-epbx is a protein; metabolism is expected to involve proteolytic degradation via catabolic pathways, similar to endogenous erythropoietin. No specific metabolic enzymes have been identified; clearance is primarily through receptor-mediated uptake and proteolysis. |
| Excretion | Primarily hepatic metabolism; ~10% excreted unchanged in urine, remainder via feces as metabolites. |
| Half-life | Terminal elimination half-life is ~2.5-4.5 hours following intravenous administration; shorter in children; prolonged in hepatic impairment. |
| Protein binding | Primarily binds to transferrin; iron is 100% bound to transferrin after dissociation from complex. |
| Volume of Distribution | Vd is approximately 0.067-0.22 L/kg; reflects distribution into plasma and extracellular fluid; limited tissue penetration initially. |
| Bioavailability | Not orally bioavailable; administered intravenously (100% bioavailability for IV route). |
| Onset of Action | Intravenous: within 5-15 minutes; oral: not applicable for this parenteral iron agent. |
| Duration of Action | Clinical effect typically persists for 24-48 hours; hemoglobin response may be seen within 1-2 weeks after full dosing. |
50-100 IU/kg intravenously or subcutaneously three times weekly; initial dose 50 IU/kg three times weekly, titrated to target hemoglobin 10-12 g/dL.
| Dosage form | INJECTABLE |
| Renal impairment | For CKD patients, epoetin alfa dosing is independent of GFR; adjust based on hemoglobin response. No specific GFR-based dose adjustments, but start at 50-100 IU/kg three times weekly for dialysis patients. |
| Liver impairment | No specific Child-Pugh based adjustments. Use with caution in severe hepatic impairment; monitor for adverse effects. |
| Pediatric use | 0.5-50 IU/kg subcutaneously or intravenously three times weekly, titrated to target hemoglobin. For pediatric CKD, initial dose 50 IU/kg three times weekly. |
| Geriatric use | No specific dose adjustment; initiate at lower end of dosing range (50 IU/kg three times weekly) and titrate slowly, monitoring for hypertension and thrombotic events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RETACRIT (RETACRIT).
| Breastfeeding | It is not known whether epoetin alfa is excreted in human milk. Endogenous erythropoietin is present in breast milk. M/P ratio not available. Caution should be exercised when Retacrit is administered to a nursing woman. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child from the drug or underlying maternal condition. |
| Teratogenic Risk | Retacrit (epoetin alfa-epbx) is a recombinant human erythropoietin. In animal studies, epoetin alfa did not demonstrate teratogenicity at clinically relevant doses. However, there are no adequate and well-controlled studies in pregnant women. Potential fetal risks include hypertension and thromboembolic events secondary to maternal polycythemia. Use during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
WARNING: INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE. Chronic Kidney Disease: In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of 13 g/dL or greater. No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks. Use the lowest dose sufficient to reduce the need for red blood cell transfusions. Cancer: ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers. To decrease these risks, as well as the risk of serious cardiovascular and thromboembolic reactions, use the lowest dose needed to avoid red blood cell transfusions. Use ESAs only for anemia from myelosuppressive chemotherapy. ESAs are not indicated for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure. Discontinue following the completion of a chemotherapy course. Perisurgery: Due to increased risk of deep venous thrombosis (DVT), use prophylactic anticoagulation and consider whether benefit of transfusion reduction outweighs increased risk of post-operative thrombotic/vascular events.
| Serious Effects |
["Uncontrolled hypertension","Pure red cell aplasia (PRCA) that begins after treatment with epoetin alfa or other ESAs","Known hypersensitivity to epoetin alfa-epbx or any component of the product"]
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| Fetal Monitoring | Monitor hemoglobin concentration weekly until stable, then periodically. Monitor blood pressure frequently during therapy. Monitor for signs of thrombotic events. In pregnant women, monitor for worsening hypertension, preeclampsia, and thromboembolic events. Consider fetal monitoring (e.g., ultrasound for growth) in women with chronic kidney disease or significant anemia. |
| Fertility Effects | No specific studies on fertility effects of Retacrit have been conducted. In animal studies with epoetin alfa, no effects on fertility were observed at clinically relevant doses. Anemia itself may impair fertility; correction of anemia with Retacrit may improve fertility in affected individuals. |
| Precautions | ["Increased mortality, myocardial infarction, stroke, and thromboembolism","Increased risk of thrombosis of vascular access","Increased mortality and/or tumor progression in cancer patients","Hypertension","Seizures","Pure red cell aplasia (PRCA) due to anti-erythropoietin antibodies","Serious allergic reactions","Possible worsening of anemia due to antibody-mediated PRCA","Risk of cardiovascular events when hemoglobin exceeds 11 g/dL","Need for iron supplementation","Monitoring of hemoglobin and blood pressure"] |