Epoetin alfa formulations

Dosage form Epogen is formulated as a sterile, buffered solution in single-dose, preservative-free vials. Each ml of solution contains 2000,3000,4000, or 10,000 units of epoetin alfa. A single-dose vial containing a more concentrated solution, 40,000 units per ml, is also available, as are multidose, preserved vials. 

Epoetin alfa, recombinant erythropoietin, is a glycoprotein that simulates erythrocyte production. Epoetin alfa is administered three times weekly subcutaneously or intravenously. Epoetin is used to treat anemia in patients with chronic renal failure, HIV infection, and patients receiving chemotherapy [104]. Development of a safe, effective nasal formulation of epoetin alfa, containing an absorption enhancer could once again improve the efficacy of epoetin alfa therapy, and reduce the number of injections required in these sensitive patient populations. 

For this reason, a drug product that is to be used multiple times (multidose) must contain a preservative to prevent bacterial growth. A list of preservatives that have been used in pharmaceutical formulations is shown in Table 2. However, most of these are not usually compatible with protein formulations. Some, such as the parabens, are not active in the presence of nonionic surfactants—excipients that are typically required in protein formulations.Others may not be acceptable for a particular route of administration. Benzalkonium chloride, a commonly used preservative in topical formulations, causes ototoxicity when applied to the ear. As with buffering species, the list of preservatives available to the formulation scientist quickly narrows to just a few compounds including benzyl alcohol, phenol, w-cresol, and benzethonium chloride. A benzyl alcohol-containing formulation of epoetin alfa has been shown to be stable, even when dispensed in plastic syringes. ... 

I. Stability of multidose, preserved formulation epoetin alfa in syringes for three and six weeks. Am. J. Health-Syst. Pharm. 2003, 60, 464-A68. 

In the past, subcutaneous epoetin alfa resulted in more pain than epoetin beta, owing to citrate buffer in the product. Although the formulation of epoetin alfa has been changed to a phosphate buffer, discomfort after epoetin alfa is still greater than after epoetin beta (115,116). 

Macdougall, I.C., Pure red cell aplasia with anti-erythropoietin antibodies occurs more commonly with one formulation of epoetin alfa than another. Curr Med Res Opin 2004, 20(1), 83-86. 

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