Drug withdrawals

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Significant U.K. medication changes in Indication for use or withdrawals of marketing authorisations[1] (Italics indicate drugs never marketed in UK, bold indicates drugs withdrawn elsewhere but still marketed in UK or reinstated or with major indication change)
Year Name Trade Name Comment
1961 thenalidine Sandostene® Agranulocytosis
1961[2] thalidomide Distavel®, Valgis®, Valgraine®,

Asmaval®, Tensival®

A sedative drug, also marketed for morning sickness that produced fetal malformation. At the time the promotional material in some markets emphasised its safety in pregnancy !. It has recently been reintroduced to the market as an immunosuppressant and is used to treat leprosy.
1961 (FDA) iproniazid Marsilid®, Iprozid®, Ipronid®, Rivivol®, Propilniazida® Hepatotoxic, the first MAOI originally developed to treat tuberculosis.
1964 benziodarone Hepatotoxicity
1966 (FDA) sulfadimethoxine Madricidin® Stevens-Johnson syndrome
1966 (FDA) aminoglutethimide Reintroduced for malignant tumours/Cushings
1968 ibufenac Hepatotoxicity
1970 chlormadinone Estalor-21®, C-Quens® Mammary tumours in dogs (FDA withdrawal 1972)
1970 megestrol Animal toxicity
1971 diethylstilbestrol (DES) stilboestrol It induced cervical and vaginal cancer in the female children of treated mothers as well as genital malformation in its previous indication to prevent miscarriage. Now used rarely to treat prostate cancer and breast cancer in postmenopausal woman. DESs use in farming practice is controversial and it has the potential to be an environmental toxin.
1975 practolol Eraldin® Fibrinous peritonitis & blindness
1975 aminopyrine Bone marrow suppression (withdrawn by FDA 1970)
1975 polidexide Long term animal toxicity
1976 (FDA) chloroform Carcinogenic potential
1977 dipyrone Dimethone® Agranulocytosis
1978 oxyphenisatine Lavema® Hepatitis, jaundice (withdrawn FDA 1973)
1979 alclofenac animal toxicity (withdrawn FDA 1973)
1979 methapyrilene Long term animal toxicity
1980 phenacetin Renal tubular necrosis, haemolytic anaemia (FDA withdrawal 1983)
1981 clioquinol Neurotoxicity (withdrawn by FDA 1973)
1982 benoxaprofen Opren® A NSAID it caused hepatotoxicity and was perhaps the most significant NSAID withdrawals before rofecoxib. There have been ten or more NSAIDs withdrawn
1982 zimeldine Zelmid® Normud® The first SSRI it caused Guillain-Barre syndrome and a hypersensitivity syndrome so was withdrawn the same year as authorised in UK.
1982 phenformin Lactic acidosis
1982 methandrostenolone endocrine side effects
1983 Indoprofen Long term animal toxicity
1983 propanidid Anaesthetic agent with hypersensitivity reactions
1983 zimeldine Normud®, Zelmid® Guillian-Barre syndrome and hypersensitivity reactions killed it within a year of launch as first SSRI
1984 oxyphenbutazone Tandearil® Blood dyscrasias (FDA withdrawal 1985)
1984 fenclofenac long term animal toxicity
1984 feprazone multiple toxicities
1986 aspirin (paediatric) Use withdrawn in children due to Reye's syndrome
1986 nomifensine Merital)® Haemolytic anaemia
1986 sulphamethoxypyridazine blood disorders
1987 danthron carcinogenic in animals. Still licensed for terminal illness
1987 suprofen Nephrotoxicity
1989 prenylamine ventricular tachycardia it was the first of many withdrawn because of torsade de pointes
1990 metipranolol eye damage
1990 tryptophan L-tryptophan eosinophilia-myalgia syndrome due to contamination (most believe)
1991 triazolam Halcion® A benzodiazepine used for sedation that produced psychiatric problems like acute psychosis, paranoia and confusion. Still licensed by FDA
1991 terodiline Micturin® Torsade de pointes
1992 temafloxacin Multiple toxicities
1997 troglitazone Romozin® UK, Rezulin® USA First glitazone on the UK market for a few months it was discontinued by Glaxo Wellcome because of hepatotoxicity. The FDA allowed it to remain until 2000 on the US market earning Warner-Lambert about $2 billion in sales and causing about 90 cases of severe hepatic failure worldwide.
1998 mibefradil Posicor® A calcium channel blocker. It interacted with far too many other drugs used for cardiological conditions which enhanced its proarrhythmic potential.
2000 cisapride Propulsid® A drug that encouraged gastric motility and fatal arrythmias.
2001 cerivastatin Lipobay® A statin with ten times the rate of myopathy than other marketed drugs of the class.
2004 rofecoxib Vioxx® Withdrawn when a cancer prevention trial confirmed suspicions that in long term use it it had a 2-3 times increased risk of myocardial infarction.[3] Coxibs subsequently have been determined by the EMEA to be contraindicated in those with ischaemic heart disease
2005(FDA) natalizumab Tysabri® An anti-α4,β1 integrin monoclonal antibody which was withdrawn before European approvial but after FDA approvial when 3 cases of progressive multifocal leukoencephalopathy had occurred amongst 3000 treated in RCT and 5000 treated in all. At the time EMEA rules were tighter than FDA rules.
2005 co-proxamol Distalgesic®, Cosalgesic® An analgesic combination of dextropropoxyphene and paracetamol which has been withdrawn because of its toxicity in overdose. Some patients found it beneficial to them, despite little evidence for acute analgesia benefit compared to paracetamol alone.
2005 valdecoxib Bextra® Withdrawn when the combination of skin reactions and not so good cardiovascular safety got too much. A coxib.
2006 ximelagatran Exanta® A potential blockbuster anticoagulant that wasn't. Withdrawn due to hepatic toxicity. License refused by FDA in 2004, but development because of potential to replace warfarin in some common indications had continued. At time of withdrawal not marketed in UK, but licensed in EU (2003) and marketed in 10 Western European countries, Brazil and Argentina.
2007 tegaserod Zelmid® Marketed widely throughout the world for upper gut dysmotility, but not in UK. FDA asked for withdrawal because of reports of cardiac ischaemia [4]
2007 lumiracoxib Prexige® Withdrawn in Australasia and Canada and a few months later in EU[5] A coxib.
2007 inhaled insulin Exubera® Withdrawn October as insufficient market penetration[6]
2007 carisoprodol Carisoma® Withdrawn in EU November 2007 due to abuse potential
2007 aprotinin Trasylol® Withdrawn in EU 2007 as outcomes worse than competing products
2008 rimonabant Acomplia® Withdrawn in EU 2008 as depression and suicide risk not predictable. Never had FDA approval.
2009 efalizumab Raptiva® Withdrawn in EU Feb 2009 due to 3 cases of progressive multifocal leukoencephalopathy[7]
2010 sibutramine Reductil® Withdrawn in EU Jan 2010 due to the required post marketing surveillance SCOUT study showing excess cardiovascular mortality [8]
2010 rosiglitazone Avandia® Withdrawn in EU Sept 2010 due to poor cardiovascular outcomes only a few years before patent expiry. In 2013 the FDA restored a full license as it appears its cardiovascular outcomes are similar to other hypoglycaemic agents (ie little, if any benefit)
2011 pioglitazone Actos® Not withdrawn in most of EU or by FDA. Withdrawn in France June 2011 due to increased risk of bladder cancer.
2011 drotrecogin alfa (activated) Xigris® Withdrawn in EU October 2011 due to poor further clinical trial results.
2012 meprobamate The EMEA recommended that all meprobamate containing products (used for anxiety) be withdrawn from the market in 2012. In the UK the last such product was withdrawn in December 2016 but some unlicensed use might have to have continued.
2013 hydroxyethyl starch intravenous infusion Withdrawal as a rescusitation fluid took place in the EU in June 2013. It was allowed to be used for acute blood loss from December 2014 but the full withdrawal process was initiated in the EU from December 2018. One reason for this appeared to be use outside license.
2017 (2014) strontium ranelate Protelos® Strontium ranelate faced increased restrictions on its use from mid 2013 when cardiovascular side effects were noted. It's indication was severely restricted by mid 2014 when excess VTE mortality was confirmed and it was withdrawn as a commercial decision at the end of 2017 in the U.K.
2016(2014) retigabine Trobalt® Withdrawal process due to low market share in its epilepsy indication started in September 2016 and was completed in June 2017. The drug had become last in line from December 2014 because of pigmentation induction.
2018 (2006) gadolinium-containing contrast agents: Omniscan and iv Magnevist Omniscan® and iv Magnevist® Gadolinium-containing contrast agents used in MRI imaging had their use reviewed in the EU. As a result in February 2018 two were with drawn and another two had use restricted to liver imaging. The issues had been noted since 2006 and as safer agents came on to the market incremental regulation took place.
2018 ulipristal acetate Esmya® Because of risk liver injury no new patients to be commenced from February 2018.
2018 (2009) daclizumab Zenapax® Withdrawal in EU March 2018 due to incidence severe autoimmune reactions in multiple sclerosis indication. It had been reintroduced to market in June 2016 after an earlier withdrawal for commercial reasons in 2009 for the first transplant indication.
2018 flupirtine Efiret®, Flupigil®, Flupirtin®, Flupirtina®, Flupirtine®, Flupizen®, Fluproxy®, Katadolon®, Metanor®, Trancolong®, Zentiva® Never marketed in UK but sometimes imported from Europe where its hepatotoxicity finally lead to withdrawal

This list is not meant to be exhaustive and can be made inaccurate by further developments in the evidence base[9]. The issues are often relative, so that a drug such as chloramphenicol has not been available in France since 1978 but is still available in UK and USA despite known risk aplastic anaemia.


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