Extemporaneously Compounded Oral Medicines in European Hospital Pharmacies Thesis submitted for the degree of Doctor of Philosophy Maria João Reis de Carvalho UCL School of Pharmacy December 2012 Extemporaneously Compounded Oral Medicines in European Hospital Pharmacies This thesis describes research conducted in the UCL School of Pharmacy between October 2006 and September 2010, under the supervision of Professor Kevin Taylor and Dr Catherine Tuleu. I certify that the research described is original and that any parts of the work that have been conducted by collaboration are clearly indicated. I also certify that I have written all the text herein and have clearly indicated by suitable citation any part of this dissertation that has already appeared in publication. ____________________________ _____________ Signature Date 2 To my grandparents Aos meus avós Maria Benedita e Humberto 3 Abstract Pharmaceutical compounding corresponds to the preparation of customised medicines in order to meet the specific needs of patients, which cannot be met by the proprietary medicines provided by the pharmaceutical industry. Historically, pharmaceutical compounding dates back to the very origins of pharmacy and, ever since, it has been an integral part of pharmacy practice. Nevertheless, little is known regarding current compounding practices in Europe and, therefore, the aim of this project was to identify and characterise the oral compounded medicines most frequently dispensed in European hospital pharmacies. The research method adopted was a large-scale, international (European) survey and the research instrument was a self-completion (country-specific) questionnaire. A total of 11 European countries were included in the research: Portugal, UK, Switzerland, Poland, Netherlands, Denmark, Slovenia, Finland, Spain, France and Germany. For most countries, a purposive sample of hospitals was contacted and invited to contribute data regarding the oral compounded medicines most frequently dispensed in their pharmacies. The pilot-study was launched in Portugal but fieldwork was undertaken in most countries. Information regarding legislation, professional organisations and information sources relevant to pharmaceutical compounding was also collected. The oral compounded medicines most frequently dispensed in hospital pharmacy varied considerably throughout Europe, from traditional cachets in Poland to complex tablets in the Netherlands and Denmark. A wide range of active substances, including NTI drugs, and dosage strengths were dispensed. Compounded medicines were prepared individually and also in batches of variable sizes. There is little consistency of compounding practices in Europe and there is a need for common legislation, professional organisations and information sources. This project corresponds to the largest and most complex research in pharmaceutical compounding across Europe and aims to contribute to the harmonisation of quality and safety of compounded medicines in Europe. Abstract | 4 Acknowledgements To my supervisors Kevin Taylor and Catherine Tuleu, for the extraordinary support, guidance and commitment to this thesis. Thank you for the expert discussions and academic skills, invaluable to my professional career. To my parents and brother, for the unconditional love and support. Thank you for the inspiration and encouragement to achieve everything in life. To Diego Romero, for the endless dedication, patience and understanding. Thank you for always being there. To Ashveena Tirvassen and Andrea Wolf, for the greatest friendships and wonderful memories in London. To João Montalvão, for the exceptional academic foundations and decisive emotional support. To Carlos Maurício Barbosa, for the continuous guidance and remarkable contributions to this thesis. To Loyd Allen, for the inspiration and encouragement towards my career on pharmaceutical compounding. To Owen Shepherd, for the friendship and opportunity to teach pharmaceutical compounding. To Catherine Baumber, for the friendship and assistance throughout this thesis. To the UCL School of Pharmacy, for the PhD research opportunity and studentship. To Farmácia Lordelo, for the support and access to compounding training in a state-of-the art laboratory. To all European pharmacists and health care professionals who contributed to this thesis. In particular, a special acknowledgement to: Jorge Brochado (Portugal); Tony Murphy, Ann Horton and Andrew Lowey (UK); Hans Stötter and Bettina Gasser (Switzerland); Małgorzata Sznitowska and Aleksandra Neubauer-Vasquez (Poland); Frits Boom and Yvonne Bouwman (Netherlands); Daniel Bar-Shalom, Trine Schnor and Line Poulsen (Denmark); Spela Godec, Tomi Laptoš and Jure Bračun (Slovenia); Anne Juppo, Hanna Tolonen and Kristine Salminen (Finland); Diego Marro, José María Herreros and Manuela Atienza (Spain); Jörg Breitkreutz (Germany). Acknowledgements | 5 Table of Contents Page Abstract ......................................................................................................... 4 Acknowledgements ....................................................................................... 5 Table of Contents ........................................................................................ 6 List of Figures ............................................................................................. 9 List of Tables ............................................................................................. 11 List of Abbreviations .................................................................................... 13 1. Introduction ........................................................................................... 16 1.1 Pharmaceutical compounding ......................................................... 16 1.2 Hospital pharmacy ........................................................................... 34 1.3 Aim and objectives ........................................................................... 38 2. Methodology ......................................................................................... 39 2.1 International survey ......................................................................... 40 2.2 Sampling methods ........................................................................... 48 2.3 Data collection ................................................................................. 54 2.4 Data processing and analysis .......................................................... 55 3. Compounding in Portugal ..................................................................... 60 3.1 Legislation ........................................................................................ 62 3.2 Professional organisations and information sources ....................... 65 3.3 Methods ........................................................................................... 68 3.4 Results and discussion .................................................................... 77 3.5 Summary ......................................................................................... 94 4. Compounding in the UK ........................................................................ 95 4.1 Legislation ........................................................................................ 98 4.2 Professional organisations and information sources ..................... 100 4.3 Methods ......................................................................................... 103 4.4 Results and discussion .................................................................. 108 4.5 Summary ....................................................................................... 122 5. Compounding in Switzerland .............................................................. 123 5.1 Legislation ...................................................................................... 125 Table of Contents | 6 5.2 Professional organisations and information sources ..................... 126 5.3 Methods ......................................................................................... 128 5.4 Results and discussion .................................................................. 131 5.5 Summary ....................................................................................... 142 6. Compounding in Poland ...................................................................... 143 6.1 Legislation ...................................................................................... 144 6.2 Professional organisations and information sources ..................... 145 6.3 Methods ......................................................................................... 146 6.4 Results and discussion .................................................................. 149 6.5 Summary ....................................................................................... 159 7. Compounding in the Netherlands ....................................................... 160 7.1 Legislation ...................................................................................... 162 7.2 Professional organisations and information sources ..................... 163 7.3 Methods ......................................................................................... 165 7.4 Results and discussion .................................................................. 170 7.5 Summary ....................................................................................... 183 8. Compounding in Denmark .................................................................