Hemocrit5000 IU pre-filled syringe

Established (FDA-approved) indications

• Anemia due to chronic kidney disease (CKD), in patients on dialysis and in patients not on dialysis, to reduce the need for red blood cell (RBC) transfusion. Hemocrit is used to raise hemoglobin only to the lowest level sufficient to avoid transfusion; it is not used to normalize hemoglobin (see Precautions and Warnings).
• Chemotherapy-induced anemia in patients with non-myeloid malignancies where the anemia is due to concomitant myelosuppressive chemotherapy and treatment is not curative in intent. Hemocrit is not indicated when chemotherapy is given with curative intent.
• Anemia related to zidovudine therapy in patients infected with HIV, when endogenous serum erythropoietin levels are ≤500 mU/mL and the zidovudine dose is ≤4200 mg/week.
• Reduction of allogeneic blood transfusion in patients with pre-operative hemoglobin between 10 and 13 g/dL who are scheduled for elective, non-cardiac, non-vascular surgery with an expectation of significant blood loss.

Not indicated for: anemia in cancer patients not receiving concurrent chemotherapy; use to achieve normalization of hemoglobin (associated with increased cardiovascular risk and, in some cancers, tumor progression); or as a substitute for emergency transfusion. Hemocrit must be prescribed and monitored by a physician.

Erythropoietin Alfa is recombinant human erythropoietin (a glycoprotein produced by recombinant DNA technology in mammalian cell culture) that is structurally and biologically similar to endogenous human erythropoietin. It is supplied as a sterile, preservative-free or multi-dose (with preservative) solution for subcutaneous or intravenous injection in single-dose vials or prefilled syringes at various strengths (commonly 2,000, 3,000, 4,000, 10,000, and 40,000 Units/mL); formulations may contain human albumin as a stabilizer.

Hemocrit is a recombinant form of human erythropoietin, the endogenous hormone that is normally produced mainly by the kidneys and stimulates the bone marrow to produce red blood cells. As an erythropoiesis-stimulating agent (ESA), Hemocrit is used to treat certain types of anemia, most importantly the anemia that develops when diseased kidneys can no longer produce enough natural erythropoietin.

Hemocrit is given only by injection (subcutaneous or intravenous), under medical supervision, with regular monitoring of hemoglobin, blood pressure, and iron status, because raising hemoglobin too high or too quickly increases the risk of serious cardiovascular events (see Precautions and Warnings).

Erythropoiesis-stimulating agent (ESA) — recombinant human erythropoietin. Hemocrit belongs to this class.

Mechanism of action

Erythropoietin Alfa stimulates erythropoiesis by binding to the erythropoietin receptor on erythroid progenitor cells in the bone marrow, triggering signaling pathways that promote proliferation, differentiation, and maturation of these cells into mature red blood cells, and reducing their apoptosis. This increases reticulocyte and, subsequently, red blood cell and hemoglobin levels, generally becoming apparent over 2–6 weeks.

Pharmacokinetics

After intravenous administration, serum concentrations decline in a biexponential manner with a mean elimination half-life of roughly 4–13 hours. After subcutaneous injection, absorption is slower, peak concentrations occur later (12–18 hours), and the apparent half-life is longer, but bioavailability is lower (roughly 20–30%) than with intravenous dosing. Erythropoietin Alfa is a large glycoprotein that is not expected to be extensively cleared by the liver or kidneys, and no formal hepatic dose-adjustment studies have been conducted.

• Hemocrit is given by subcutaneous or intravenous injection only; it is not given orally, intramuscularly, or by IV push without proper technique.
• Do not shake the vial or syringe — vigorous shaking can denature the protein and reduce activity.
• Visually inspect for particulate matter and discoloration before use; the solution should be colorless and clear. Discard if discolored or if particles are seen.
• Single-dose vials and prefilled syringes contain no preservative — use one dose per vial/syringe and discard any unused portion; do not re-enter a used vial.
• Hemocrit should be administered under the supervision of a physician familiar with its use, with periodic monitoring of hemoglobin, blood pressure, and iron studies.

• Iron deficiency: Adequate iron stores are required for an adequate response to Hemocrit; most patients require supplemental iron during therapy, and iron deficiency should be corrected for Hemocrit to work as expected.
• Antihypertensive therapy: Because Hemocrit commonly raises blood pressure, patients on antihypertensive medications may need dose adjustment of those medications, and blood pressure must be monitored closely, especially early in treatment.
• Other erythropoiesis-stimulating agents: Hemocrit should not be substituted for, or interchanged with, other ESAs in a patient who develops pure red cell aplasia (PRCA), because antibodies formed against one ESA typically cross-react with others (see Contraindications).
• Hemocrit is a large protein eliminated primarily through receptor-mediated and cellular pathways; no clinically significant cytochrome P450-mediated drug interactions are known.

Common adverse reactions

Serious adverse reactions

Serious risks associated with Hemocrit include an increased risk of death, myocardial infarction, stroke, and venous thromboembolism when hemoglobin targets exceed conservative thresholds; increased risk of tumor progression or recurrence when used in certain cancers; seizures (more frequent in the first several months of chronic kidney disease treatment); pure red cell aplasia (rare); and serious allergic reactions. See Precautions and Warnings for full detail.

Pregnancy: Data on the use of Hemocrit in pregnant women are limited. Hemocrit should be used during pregnancy only if clearly needed and the potential benefit justifies the potential risk to the fetus; a physician should be consulted before use in pregnancy.

Lactation: It is not known whether Hemocrit is excreted in human milk, and the effects on a breastfed infant are not established. Because endogenous erythropoietin is a normal component of human milk, the clinical significance of exposure from Hemocrit is unclear; a physician should be consulted to weigh the benefits of breastfeeding against any potential risk before using Hemocrit while breastfeeding.

Boxed warning

• Increased mortality and cardiovascular/thromboembolic risk: Erythropoiesis-stimulating agents, including Hemocrit, increase the risk of death, myocardial infarction, stroke, and venous thromboembolism when hemoglobin targets exceed conservative thresholds. Use the lowest dose of Hemocrit sufficient to reduce the need for RBC transfusion; do not use Hemocrit to normalize hemoglobin.
• Tumor progression/recurrence: In patients with cancer, Hemocrit has been associated with shortened overall survival and/or increased risk of tumor progression or recurrence in some studies when dosed to a hemoglobin target above that needed to avoid transfusion. Hemocrit is not indicated when chemotherapy is given with curative intent, and should be discontinued following completion of a chemotherapy course.

Other warnings and precautions

• Hypertension: Blood pressure may rise, and hypertensive crisis can occur, particularly with rapid hemoglobin rises; monitor and control blood pressure before and during treatment.
• Seizures: Seizures have been reported, especially during the first several months of treatment for chronic kidney disease; use caution in patients with a seizure history and monitor for premonitory neurologic symptoms.
• Pure red cell aplasia (PRCA): Cases of antibody-mediated PRCA have been reported after months to years of therapy; evaluate patients with a sudden loss of response (progressive anemia with low reticulocyte count while on stable dosing) for PRCA and discontinue Hemocrit if confirmed (see Contraindications).
• Hypersensitivity: Serious allergic reactions, including anaphylaxis, angioedema, bronchospasm, and skin reactions, have been reported; discontinue immediately if a serious reaction occurs.
• Regularly monitor hemoglobin, blood pressure, and iron status throughout treatment with Hemocrit.

Doses of Hemocrit above those needed for the desired hemoglobin/erythropoiesis effect can lead to polycythemia (excessive erythrocytosis) with associated hyperviscosity and increased risk of serious cardiovascular events (e.g., severe hypertension, thrombosis). There is no specific antidote for Hemocrit overdose. If hemoglobin rises excessively, Hemocrit should be withheld and, if necessary, phlebotomy performed to reduce red cell mass, with supportive care as clinically indicated. Anyone who suspects an overdose of Hemocrit should seek immediate medical attention or contact emergency services.

Store Hemocrit refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze; discard any vial that has been frozen. Do not shake. Protect from light by keeping in the original carton until time of use. Keep out of reach of children.

• Renal impairment: Hemocrit is the primary treatment for anemia caused by chronic kidney disease; dosing is titrated by hemoglobin response rather than by a fixed renal-function-based adjustment (see Dosage and Administration).
• Hepatic impairment: No dedicated hepatic dose-adjustment studies have been conducted; use with the same hemoglobin-guided titration and monitoring as in other patients.
• Elderly patients: Clinical studies have not identified differences in response between elderly and younger patients, but cardiovascular risk should be considered given the boxed warning.
• Pediatric patients: Use in pediatric patients with anemia of chronic kidney disease is supported by clinical experience with weight-based, hemoglobin-titrated dosing (see Pediatric Uses); safety and efficacy for chemotherapy-induced anemia in children have not been established.
• Patients with hypertension: Hemocrit should be used with caution and blood pressure adequately controlled before starting therapy (see Contraindications and Precautions and Warnings).

Duration of Hemocrit therapy depends on the indication. For anemia of chronic kidney disease, treatment is generally long-term and ongoing, with the dose adjusted periodically to maintain the lowest hemoglobin level sufficient to avoid transfusion. For chemotherapy-induced anemia, Hemocrit is used only for the duration of the myelosuppressive chemotherapy course and should be discontinued after its completion, or sooner if hemoglobin has not risen adequately after 8 weeks. For zidovudine-associated anemia, response is reassessed after 8 weeks. For pre-surgical use, Hemocrit is given as a short, defined course before and around the time of surgery. The treating physician determines the exact duration based on response and clinical context.

Erythropoiesis-stimulating agents (ESAs); Hematopoietic growth factors; Recombinant human erythropoietins

Erythropoietin Alfa binds to the erythropoietin receptor on erythroid progenitor cells in the bone marrow, stimulating their proliferation, differentiation, and survival, which increases the production and release of mature red blood cells.

C

Hemocrit is used in pediatric patients with anemia due to chronic kidney disease, including those on dialysis, with dosing individualized by body weight and titrated to hemoglobin response, similar in principle to adult dosing. The safety and effectiveness of Hemocrit for chemotherapy-induced anemia in pediatric patients have not been established, and its use for this purpose is not recommended outside expert pediatric oncology guidance.