COMMITTEE OF EXPERTS ON THE CLASSIFICATION OF MEDICINES AS REGARDS THEIR SUPPLY (CD-P-PH/PHO) Report classification/justification of - Medicines belonging to the ATC group M01 (Antiinflammatory and antirheumatic products) Table of Contents Page INTRODUCTION 6 DISCLAIMER 8 GLOSSARY OF TERMS USED IN THIS DOCUMENT 9 ACTIVE SUBSTANCES Phenylbutazone (ATC: M01AA01) 11 Mofebutazone (ATC: M01AA02) 17 Oxyphenbutazone (ATC: M01AA03) 18 Clofezone (ATC: M01AA05) 19 Kebuzone (ATC: M01AA06) 20 Indometacin (ATC: M01AB01) 21 Sulindac (ATC: M01AB02) 25 Tolmetin (ATC: M01AB03) 30 Zomepirac (ATC: M01AB04) 33 Diclofenac (ATC: M01AB05) 34 Alclofenac (ATC: M01AB06) 39 Bumadizone (ATC: M01AB07) 40 Etodolac (ATC: M01AB08) 41 Lonazolac (ATC: M01AB09) 45 Fentiazac (ATC: M01AB10) 46 Acemetacin (ATC: M01AB11) 48 Difenpiramide (ATC: M01AB12) 53 Oxametacin (ATC: M01AB13) 54 Proglumetacin (ATC: M01AB14) 55 Ketorolac (ATC: M01AB15) 57 Aceclofenac (ATC: M01AB16) 63 Bufexamac (ATC: M01AB17) 67 2 Indometacin, Combinations (ATC: M01AB51) 68 Diclofenac, Combinations (ATC: M01AB55) 69 Piroxicam (ATC: M01AC01) 73 Tenoxicam (ATC: M01AC02) 77 Droxicam (ATC: M01AC04) 82 Lornoxicam (ATC: M01AC05) 83 Meloxicam (ATC: M01AC06) 87 Meloxicam, Combinations (ATC: M01AC56) 91 Ibuprofen (ATC: M01AE01) 92 Naproxen (ATC: M01AE02) 98 Ketoprofen (ATC: M01AE03) 104 Fenoprofen (ATC: M01AE04) 109 Fenbufen (ATC: M01AE05) 112 Benoxaprofen (ATC: M01AE06) 113 Suprofen (ATC: M01AE07) 114 Pirprofen (ATC: M01AE08) 115 Flurbiprofen (ATC: M01AE09) 116 Indoprofen (ATC: M01AE10) 120 Tiaprofenic Acid (ATC: M01AE11) 121 Oxaprozin (ATC: M01AE12) 125 Ibuproxam (ATC: M01AE13) 128 Dexibuprofen (ATC: M01AE14) 129 Flunoxaprofen (ATC: M01AE15) 134 Alminoprofen (ATC: M01AE16) 135 Dexketoprofen (ATC: M01AE17) 136 Naproxcinod (ATC: M01AE18) 140 Ibuprofen, Combinations (ATC: M01AE51) 141 Naproxen and Esomeprazole (ATC: M01AE52) 146 Ketoprofen, Combinations (ATC: M01AE53) 153 Naproxen and Misoprostol (ATC: M01AE56) 157 3 Mefenamic Acid (ATC: M01AG01) 158 Tolfenamic Acid (ATC: M01AG02) 164 Flufenamic Acid (ATC: M01AG03) 169 Meclofenamic Acid (ATC: M01AG04) 170 Celecoxib (ATC: M01AH01) 171 Rofecoxib (ATC: M01AH02) 178 Valdecoxib (ATC: M01AH03) 179 Parecoxib (ATC: M01AH04) 180 Etoricoxib (ATC: M01AH05) 187 Lumiracoxib (ATC: M01AH06) 195 Polmacoxib (ATC: M01AH07) 197 Nabumetone (ATC: M01AX01) 198 Niflumic acid (ATC: M01AX02) 201 Azapropazone (ATC: M01AX04) 204 Glucosamine (ATC: M01AX05) 205 Benzydamine (ATC: M01AX07) 207 Glucosaminoglycan Polysulfate (ATC: M01AX12) 208 Proquazone (ATC: M01AX13) 209 Orgotein (ATC: M01AX14) 210 Nimesulide (ATC: M01AX17) 211 Feprazone (ATC: M01AX18) 214 Diacerein (ATC: M01AX21) 215 Morniflumate (ATC: M01AX22) 218 Tenidap (ATC: M01AX23) 221 Oxaceprol (ATC: M01AX24) 222 Chondroitin Sulfate (ATC: M01AX25) 224 Avocado and Soyabean Oil, Unsaponifiables (ATC: M01AX26) 226 Feprazone, Combinations (ATC: M01AX68) 228 Phenylbutazone and Corticosteroids (ATC: M01BA01) 229 Dipyrocetyl and Corticosteroids (ATC: M01BA02) 231 4 Acetylsalicylic Acid and Corticosteroids (ATC: M01BA03) 232 Other Antiinflammatory/Antirheumatic Agents in Combination with Other Drugs (ATC: M01BX) 233 Oxycinchophen (ATC: M01CA03) 235 Sodium Aurothiomalate (ATC: M01CB01) 236 Sodium Aurotiosulfate (ATC: M01CB02) 240 Auranofin (ATC: M01CB03) 241 Aurothioglucose (ATC: M01CB04) 245 Aurotioprol (ATC: M01CB05) 246 Penicillamine (M01CC01) 247 Bucillamine (ATC: M01CC02) 254 Other specific Antirheumatic Agents (ATC: M01CX) 255 LIST OF AUTHORS 256 5 INTRODUCTION The availability of medicines with or without a medical prescription has implications on patient safety, accessibility of medicines to patients and responsible management of health care expenditure. The decision on prescription status and related supply conditions is a core competency of national health authorities. The conditions of the supply of medicines vary considerably in Council of Europe member states, due to the fact that the provisions are differently interpreted and implemented by the member states, and that important additional classification criteria are not harmonised. The Committee of Experts on the Classification of Medicines as regards their Supply (CD-P- PH/PHO)1 is co-ordinated by the European Directorate for the Quality of Medicines and HealthCare (EDQM, Council of Europe) and its working programme is based on Committee of Ministers Resolution CM/Res(2018)1 on the classification of medicines as regards their supply2. In its work, the CD-P-PH/PHO focuses on public health promotion and uses scientific approaches, taking account of the national assessments of direct and indirect risks which may occur under normal treatment conditions and under medical surveillance, as well as from foreseeable misuse or abuse of medicines. The CD-P-PH/PHO issues twice a year recommendations to health authorities of Council of Europe member states (EU and non-EU member states) on the classification of medicines and establishes good classification practices. The recommendations are also useful for pharmaceutical manufacturers and commercial operators of mail-order trade in medicines where such trade is legal. A pioneer in this field, Council of Europe bodies have been concerned since 1961 with issues relating to the classification of medicines into prescription and non-prescription medicines and have inspired relevant EU legislation. The classification criteria set out in the Council of Europe resolutions have been supplanted by Directives 92/26/CEE and 2001/83/EC (art. 70-75). Directive 2001/83/EC refers to the Council of Europe in its Whereas 32: “It is therefore appropriate, as an initial step, to harmonise the basic principles applicable to the classification for the supply of medicinal products in the Community or in the Member State concerned, while taking as a starting point the principles already established on this subject by the Council of Europe”3. It is important to note that: - The CD-P-PH/PHO does not issue recommendations on the classification of particular medicines, but on active substances used in a medicine for a specific therapeutic purpose. - In its work, the CD-P-PH/PHO uses the Anatomical Therapeutic Chemical (ATC) classification maintained by the WHO Collaborating Centre for Drug Statistics Methodology4 to identify active substances or combinations of active substances. - The CD-P-PH/PHO does not give advice relating to pending marketing authorisation procedures. 1 http://go.edqm.eu/PHO 2 http://go.edqm.eu/CMRes20181 3 https://goo.gl/at4RZo 4 https://goo.gl/KvqKir 6 The CD-P-PH/PHO supervises a database (i.e. Melclass1), hosted by the EDQM, which stores the recommendations that the Committee of Experts issues twice a year to health authorities of the Council of Europe member states which are parties to the Convention on the Elaboration of a European Pharmacopoeia, as well as national information about the classification status and supply conditions of medicines in these member states. The information is publicly available. Recommendations about 2300 medicines are published in the Melclass database. Providing a platform for dialogue and consensus building on the supply conditions of medicines in Europe as facilitated by Council of Europe Committee of Ministers Resolution CM/Res(2018)1, the CD-P-PH/PHO promotes patient safety and, where appropriate, access to medicines without a prescription across Europe, which helps to foster public health and to responsibly manage healthcare resources. 1 https://melclass.edqm.eu/ 7 DISCLAIMER This document is published for information only. The reports included in this document have no legal status and no binding character. They reflect the debates and conclusions of the reviews of scientific classifications of medicines that took place at the 62nd and 63rd meetings of the CD-P-PH/PHO (May and November 2017, respectively). The document was reviewed and endorsed by the CD-P-PH/PHO at its 64th meeting (April 2018). The reviews carried out do not commit the parent authorities of the experts nor the Council of Europe/EDQM. 8 GLOSSARY OF TERMS USED IN THIS DOCUMENT ACE Angiotensin-converting enzyme ALT Alanine aminotransferase ARF Acute renal failure ASA Acetylsalicylic acid AST Aspartate aminotransferase ATC Anatomical Therapeutic Chemical classification 1 AUC Area under curve CABG Coronary artery bypass grafting CBC Complete blood count CgA Chromogranin A CHMP Committee for Medicinal Products for Human Use Coordination Group for Mutual Recognition and Decentralised CMDh Procedures - Human CNS Central nervous system COX Cyclooxygenase CYP Cytochromes EE Ethinyl estradiol EMA European Medicines Agency FDA Food and Drug Administration GI Gastrointestinal HMA Heads of Medicines Agencies HRT Hormone replacement therapy IM Intramuscular INR International normalised ratio IV Intravenous LDH Lactate dehydrogenase MI Myocardial infarction MS Maximal strength MDD Maximal daily dose MQP Maximal quantity per pack MRI Mutual recognition information NO Naproxen-based nitric oxide NSAID Non-steroidal antiinflammatory drug OA Osteoarthritis OTC Over-the-counter (medicine supplied without prescription) PDR Physicians’ Desk Reference PIL Patient information leaflet POM Prescription only medicine PPI Proton pump inhibitors PRAC Pharmacovigilance Risk Assessment Committee RA Rheumatoid arthritis SGOT Serum glutamic oxaloacetic transaminase SGPT Serum glutamic pyruvic transaminase SLE Systemic lupus erythematosus SmPC Summary of product characteristics Classification used throughout this document Following the stipulations of Resolution