Our French sister publication La Revue Prescrire annually publishes an overview of ‘drugs to be avoided’. Although these drugs have market authorisation, their efficacy is often unproven, and they may have serious or frequent side-effects, and all in all they do more harm than good. The purpose of the list is to inform general practitioners, specialists and pharmacists about these drugs and to prevent them being prescribed to patients. The article presented in this issue of Gebu is the first in a series based on the overview of drugs to be avoided, and has been adapted to the Dutch situation. Each instalment will discuss drugs from one pharmaceutical category. The present article first presents a general explanation of the systematic procedure followed in drawing up the list, after which the first category, those for cardiovascular diseases, is discussed. (Gebu 2017; 51: 79-84)
The overview lists drugs with an unfavourable balance between efficacy and side-effects for the applications for which they have been authorised.
Drugs with no proven efficacy but with serious side-effects, or drugs whose efficacy is comparable to that of other drugs for the same application but which have more side-effects, should not be prescribed by specialists or automatically continued by GPs. Registration authorities and health agencies should undertake concrete steps to protect patients and promote the use of treatments with an acceptable balance between efficacy and side-effects. They could also apply stricter requirements when it comes to proving the efficacy of a drug on hard endpoints, in case a drug is authorised on the basis of favourable findings on surrogate endpoints. Drugs are currently being put on the market without proof that their efficacy is greater than that of comparable drugs that are already on the market. It is sufficient that their efficacy is equivalent, and the margins for equivalence are often very wide. In addition, the studies used to apply for market authorisation yield insufficient data to fully map the side-effects of a drug. If in practice the drug proves to have more, or more serious, side-effects after all, it is not easy to have the authorisation withdrawn.
A positive development is that these ‘drugs to be avoided’ are not commonly included in Dutch guidelines. Nevertheless, although their use in actual practice appears to be limited, in absolute numbers it still involves tens of thousands of patients. Professional associations could be even more reticent about including new drugs in their guidelines. It is only after their efficacy has been proven in multiple randomised studies on hard endpoints that new drugs should be definitively included in guidelines. If medical practitioners fully adhered to such guidelines, drugs with unproven efficacy and possibly unknown serious side-effects would hardly ever be used.
- GIP-databank. Raming Zvw-populatie 2015. Via: www.gipdatabank.nl.
- Productinformatie aliskiren (Rasilez®). Via: www.ema.europa.eu, human medicines, EPAR’s. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/000780/WC500047005.pdf.
- KNMP Kennisbank, via: KNMP Kennisbank online.
- Multidisciplinaire richtlijn ‘Cardiovasculair risicomanagement, herziening 2011’. Utrecht: Nederlands Huisartsengenootschap 2011. https://www.nvvc.nl/media/richtlijn/106/2011_MDR_CVRM.pdf.
- Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31: 1281-1357.
- European Medicine Agency. Questions and answers on the review of medicines containing fibrates. Outcome of a procedure under Article 31 of Directive 2001/83/EC. Februari 2011. Via: www.ema.europe.eu. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Fibrates_31/WC500098373.pdf.
- Productinformatie ivabradine (Procoralan®). Via: www.ema.europa.eu, human medicines, EPAR’s. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000597/human_med_000995.jsp&mid=WC0b01ac058001d124.
- Swedberg K, Komajda M, Böhm M, Borer JS, Ford I, Dubost-Brama A, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010; 376: 875-885.
- Agence nationale de sécurité du médicament et des produits de santé. Procoralan (ivabradine) : modifications des conditions de prescription et de délivrance et renforcement du suivi des patients - Point d'Information 2017. Via: http://ansm.sante.fr/S-informer/Points-d-information-Points-d-information/Procoralan-ivabradine-modifications-des-conditions-de-prescription-et-de-delivrance-et-renforcement-du-suivi-des-patients-Point-d-Information.
- European Medicines Agency. European Medicines Agency recommends measures to reduce risk of heart problems with Corlentor/Procoralan (ivabradine) 2014. Via: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/11/news_detail_002217.jsp&mid=WC0b01ac058004d5c1.
- Rutten FH, Bohnen AM, Schreuder BP, Pupping MDA, Bouma M. NHG-Standaard Stabiele angina pectoris (Tweede herziening). Huisarts Wet 2004; 47: 83-95.
- NHG-Standaard Hartfalen (Tweede herziening). Hoes AW, Voors AA, Rutten FH, Van Lieshout J, Janssen PGH, Walma EP. Huisarts Wet 2010; 53: 368-389.
- Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur Heart J 2016; 37: 2129-2200.
- 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013; 34: 2949-3003.
- Bijlage 2 bij de Regeling zorgverzekering. Via: https://www.farmacotherapeutischkompas.nl/algemeen/regeling-zorgverzekering. https://www.farmacotherapeutischkompas.nl/algemeen/regeling-zorgverzekering#bijlage-2-bij-de-regeling-zorgverzekering.
- Productinformatie nicorandil (Ikorel®). Via: www.cbg-meb.nl, geneesmiddeleninformatiebank. https://db.cbg-meb.nl/ords/f?p=111:3:0:SEARCH:NO::P0_DOMAIN,P0_LANG,P3_RVG1:H,NL,15221.
- The IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet 2002; 359: 1269-1275.
- Productinformatie olmesartan (Olmetec®). Via: www.cbg-meb.nl, geneesmiddeleninformatiebank.
- Rubio-Tapia A, Herman ML, Ludvigsson JF, Kelly DG, Mangan TF, Wu TT, et al. Severe spruelike enteropathie associated with olmesartan. Mayo Clin Proc 2012; 87: 732-738.
- Basson M, Mezzarobba M, Weill A, Ricordeau P, Allemand H, Alla F, et al. Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study. Gut 2016; 65: 1664-1669.
*The literature refers to the Dutch text