Introduction: This study investigates the drug selection and dispensing behaviour of hospital pharmacists of intravenous iron products including iron sucrose and iron sucrose similar, with special emphasis on substitution and interchangeability in France and Spain. Iron– carbohydrate complex drugs represent different available intravenous iron drugs and are part of the non-biological complex drug (NBCD) class, an expanding drug class with up to 30 brands available in intravenous pharmacotherapy and over 50 in clinical development. Follow-on versions of iron sucrose have appeared in some markets such as France and Spain, which were authorised by the generic approval pathway. However, differences in clinical efficacy and safety of iron sucrose similars compared with the reference originator drug Venofer have been observed, putting a question mark on their equivalence as assessed for authorisation and consequently their substitutability and interchangeability.
Method: 70 French and 70 Spanish hospital pharmacists were surveyed via an online questionnaire on their formulary selection and dispensing behaviour of intravenous iron medicines.
Results: There is little awareness about the characteristics of this class of drugs and the reported differences in safety and efficacy between iron sucrose and iron sucrose similars. In approximately 85% of cases the intravenous iron is chosen according to the hospital formulary. In 30% (France) and 34% (Spain) of cases an iron sucrose similar was dispensed because the formulary requires dispensing an alternative lower cost drug when available. In 26% (France) and 52% (Spain) of cases the physician is not informed on such a medication change using a similar product.
Conclusions: Evaluation of NBCD similars for substitution and interchange by hospital pharmacists is rarely based on scientific and clinical criteria but rather on cost aspects only, which does not ensure safe, efficacious and cost-effective use of such drugs.
Crommelin DJA, de Vlieger JSB, Weinstein V, et al. Different pharmaceutical products need similar terminology. AAPS J 2014;16:11–14.
Rottembourg JB, Kadri A, Leonard E, et al. Do two intravenous iron sucrose preparations have the same efficacy? Nephrol Dial Transplant 2011;26:3262–7.
Agüera ML, Martin-Malo A, Alvarez-Lara MA, et al. Efficiency of original versus generic intravenous iron formulations in patients on haemodialysis. PLoS ONE 2015;10:e0135967.
Barot BS, Parejiya PB, Mehta DM, et al. Physicochemical and structural characterization of iron-sucrose formulations: a comparative study. Pharm Dev Technol 2014;19:513–20.
Toblli JE, Cao G, Oliveri L, et al. Comparison of oxidative stress and inflammation induced by different intravenous iron sucrose similar preparations in a rat model. Inflamm Allergy Drug Targets 2012;11:66–78.
Toblli JE, Cao G, Angerosa M. Nitrosative stress and apoptosis in non-anemic healthy rats induced by intravenous iron sucrose similars versus iron sucrose originator. BioMetals 2015;28:279–92.
Toblli JE, Cao G, Oliveri L, et al. Differences between the original iron sucrose complex Venofer® and the iron sucrose similar Generis®, and potential implications. Port J Nephrol Hypert 2009;23:53–63.
Meier T, Schropp P, Pater C, et al. Physicochemical and toxicological characterization of a new generic iron sucrose preparation. Arzneimittelforschung 2011;61:112–19.
Martin-Malo A, Merino A, Carracedo J, et al. Effects of intravenous iron on mononuclear cells during the haemodialysis session. Nephrol Dial Transplant 2012;27:2465–71.
Lee ES, Park BR, Kim JS, et al. Comparison of adverse event profile of intravenous iron sucrose and iron sucrose similar in postpartum and gynecologic operative patients. Curr Med Res Opin 2013;29:1–7.
European Medicines Agency (EMA). Reflection paper on the data requirements for intravenous iron-based nano-colloidal products developed with reference to an innovator medicinal product. 2015. http://www.ema.europa.eu/docs/en_GB/ document_library/Scientific_guideline/2015/03/WC500184922.pdf
European Medicines Agency (EMA). Reflection paper on non-clinical studies for generic nanoparticle iron medicinal product applications. 2011. http://www.ema. europa.eu/docs/en_GB/document_library/Scientific_guideline/2011/04/ WC500105048.pdf
European Medicines Agency (EMA). Reflection paper on the data requirements for intravenous liposomal products developed with reference to an innovator liposomal product. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_ guideline/2013/03/WC500140351.pdf
European Medicines Agency (EMA). Joint MHLW/EMA reflection paper on the development of block copolymer micelle medicinal products Joint MHLW/EMA reflection paper on the development of block copolymer micelle medicinal products Table of contents. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/ Scientific_guideline/2013/02/WC500138390.pdf
Bourdon O, Ekeland C, Brion F. Pharmacy education in France. Am J Pharm Educ 2008;72:132.
EAHP. Spanish Society of Hospital Pharmacists. 2016. http://www.eahp.eu/about-us/ members/spain
Bailie GR. Comparison of rates of reported adverse events associated with i.v. iron products in the United States. Am J Health Syst Pharm 2012;69:310–20.
Beguin Y, Jaspers A. Iron sucrose—characteristics, efficacy and regulatory aspects of an established treatment of iron deficiency and iron-deficiency anemia in a broad range of therapeutic areas. Expert Opin Pharmacother 2014;15:2087–103.
Chertow GM, Mason PD, Vaage-Nilsen O, et al. On the relative safety of parenteral iron formulations. Nephrol Dial Transplant 2004;19:1571–5.
Chertow GM, Mason PD, Vaage-Nilsen O, et al. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant 2006;21:378–82.
Mühlebach S, Flühmann B. Iron carbohydrate complexes: characteristics and regulatory challenges. In: Non-biological complex drugs. Eds: Crommelin DJA, de Vlieger JSB. Springer International Publishing, 2015:149–70.
Griffith N, McBride A, Stevenson JG, et al. Formulary selection criteria for biosimilars: considerations for US health-system pharmacists. Hosp Pharm 2014;49:813–25.
Boone N, Kuy HVD, Scott M, et al. How to select a biosimilar. Eur J Hosp Pharm 2013;20:275–86.
Schellekens H, Klinger E, Mühlebach S, et al. The therapeutic equivalence of complex drugs. Regul Toxicol Pharmacol 2011;59:176–83.