Volume 3 | Number 3 Article 87 2012 Withdrawing Drugs in the U.S. Versus Other Countries Benson Ninan Albert I. Wertheimer Follow this and additional works at: http://pubs.lib.umn.edu/innovations Recommended Citation Ninan B, Wertheimer AI. Withdrawing Drugs in the U.S. Versus Other Countries. Inov Pharm. 2012;3(3): Article 87. http://pubs.lib.umn.edu/innovations/vol3/iss3/6 INNOVATIONS in pharmacy is published by the University of Minnesota Libraries Publishing. Commentary POLICY Withdrawing Drugs in the U.S. Versus Other Countries Benson Ninan, Pharm.D.1 and Albert I Wertheimer, PhD, MBA2 1Pharmacy Intern, Rite Aid Pharmacies, Philadelphia, PA and 2Temple University School of Pharmacy, Philadelphia PA Key Words: Drug withdrawals, dangerous drugs, UN Banned Drug list Abstract Since 1979, the United Nations has maintained a list of drugs banned from sale in member countries. Interestingly, there are a number of pharmaceuticals on the market in the USA that have been banned elsewhere and similarly, there are some drug products that have been banned in the United States, but remain on the market in other countries. This report provides a look into the policies for banning drug sales internationally and the role of the United Nations in maintaining the master list for companies and countries to use for local decision guidance. Background recently updated issue is the fourteenth issue, which contains At present, one of the leading causes of death in the U.S. is data on 66 new products with updated/new information on believed to be adverse drug reactions.1-14 More than 20 22 existing products. An update of the fourteenth issue was million patients have taken at least 1 of the 5 drugs published in 2010 adding 99 more products to the List by the withdrawn from the market between September 1997 and actions of 38 governments.3 September 1998. Seven drugs that were approved in 1993 and were withdrawn shortly later have contributed to 1002 In 1985 the United Nations Secretariat, in conjunction with deaths.14 A study in 2002, showed that out of the 548 drugs the World Health Organization (WHO) and the United Nations that were approved in the U.S. between 1975-1999, fifty six Environment Program (UNEP) met at the first inter-agency (10.2 %) of them required a new black box warning or were meeting and executed the first review of the List. The review withdrawn.12 Thus, it is very important that the consumer as outlined key points such as arrangements for the preparation well as the practitioner become aware of dangerous drugs. of future issues, the need for criteria for determining the inclusion of products, the question of the legal and public In 1979 the United Nations General Assembly first brought up health context of regulatory actions that were not included in the question of establishing a list of banned pharmaceutical the first issue of the List and the treatment of commercial products that could be exchanged between nations. Under data.2 Ever since then the List has been updated annually resolution 37/137 (Annex I) of December 17 1982, the making the information available to users through direct General Assembly requested the Secretary-General to internet access. organize the Consolidated List of Products Whose Consumption and/or Sale Have Been Banned, Withdrawn, Introduction Severely restricted or Not Approved by Governments. The List Since 1995 the List was divided into two separate issues, one is a continuing effort by the United Nations to circulate focusing on pharmaceuticals and the other on chemicals, information on products that are harmful to health and the which are published in alternate years. The pharmaceuticals environment.2 are further separated into monocomponent products, combination products and group products.2 This paper will The first issue of the List covered less than 500 products only focus on the 151 monocomponent pharmaceuticals that regulated by 60 governments. The fifth issue which covered were withdrawn and why they were withdrawn by the U.N. both pharmaceuticals and chemicals, included over 700 and by specific countries such as the USA, Japan, UK, Sweden products regulated by 94 governments. By the eleventh and and Australia. twelfth editions, the List had grown to include more than 1100 products regulated by 115 states.2 At present the most More specifically, this paper will compare the drugs banned in the U.S. versus the drugs banned in other prominent countries. Do we have similar policies on which drugs to Corresponding author: Albert I Wertheimer, PhD, MBA withdraw or, does the U.S. act on its own when it comes to Temple University School of Pharmacy drug withdrawal? Philadelphia PA 1 9140; [email protected] While the U.N. may outlaw a certain drug, it is possible that the banned drug may be still available in certain countries. In http://z.umn.edu/INNOVATIONS 2012, Vol. 3, No. 3, Article 87 INNOVATIONS in pharmacy 1 Commentary POLICY addition, this paper will investigate any lag time that may benefit that drug companies/ government get from keeping a occur between the issue date of withdrawal by the U.N. and drug on the market. An example of a drug that has continued the actual date it was removed from the specific country. It is to be kept on the market is the anti-diabetic drug, important to note that if a product is not listed as regulated rosiglitazone (Avandia). A drug might also be kept on the by a country it does not necessarily mean that it is permitted market in one country because it has a legitimate medical in the country. It is highly possible that some information has use, while in another country it may not be used medically not been communicated to the U.N.2 as well. and therefore is banned. For example, flunitrazepam, commonly known as the date rape drug “roofies”, is used for Drugs Banned in the U.S. the treatment of insomnia in many European countries. In the United States of America, The Center for Drug However, the FDA has not approved the use of flunitrazepam Evaluation and Research (CDER) a part of the U.S. Food and and it has deemed it an illegal substance.2 Drug Administration (FDA) is in charge of evaluating new drugs for safety and effectiveness before they may be sold. Figure 1 also shows that only 19% of drugs were banned After the drugs are on the market, CDER acts as a watchdog, worldwide. This shows the lack of agreement on which drugs monitoring for any side effects and for any unexpected health should be banned globally. It seems as if drugs that were risks. Sometimes drugs have to be withdrawn from the banned worldwide had to have severe fatal adverse effects market due to severe unwanted side effects that may be before they reached the eyes of the entire world. Drugs such fatal. In 2005, new molecular entities (NME) such as as Fen-Fen which contained fenfluramine and phentermine valdecoxib, pemoline, and technetium (99m Tc) fanolesomab were mainly removed after 20 years in the U.S. market due to were all removed due to increased risk of serious adverse a lawsuit which totaled over $13 billion in legal damages and effects. Valdecoxib, a COX-2 selective inhibitor was removed of course potential fatal pulmonary hypertension and heart from the market due to increased risk of skin reactions and valve problems.10 Both fenfluramine and its d-enantiomer, cardiovascular events. Likewise pemoline, a CNS stimulant dexafluramine (Redux) were withdrawn in September 1997 used for treatment of ADHD was removed because of fatal worldwide. The second drug that made up Fen-fen, hepatoxicity2 (See appendix for more drugs that were phentermin was banned in Sweden and the United Kingdom removed in the U.S., Internationally, and worldwide). in 1981 and 2000 respectively. However, it is still marketed widely in the U.S. 2 Figure 1 shows the percentage of the 151 drugs we studied Figure 2. that were removed in the U.S. compared to the drugs that were removed internationally and worldwide. Figure 1. Banned Internationally 17% but available in U.S. Percentage of Drugs Banned Drugs Banned Worldwide 19% US Banned but available 9% Internationally Internationally Banned 79% Drugs 0% 5% 10% 15% 20% US Banned Drugs 67% Figure 2 compares the drugs that were banned in the U.S. but are available internationally versus the drugs that are banned 0% 20% 40% 60% 80% 100% internationally but are available in the U.S. It shows that 9 % of the drugs banned by the U.S. are available in the Only 67 % of the 151 drugs that were on the List were banned international market. On the other hand, of the drugs banned by the U.S, while internationally 79 % were banned. This internationally, 17 % are available in the U.S. This goes to shows clearly that the U.S is not in complete agreement with show again that the policies of the U.S. may tend to be the other countries on which drugs should be banned. There different than the rest of the World. Of the 17 % are many reasons why the policies of the U.S may differ from internationally banned drugs, three of the drugs are from the the international world. One reason might be a monetary same class of drugs, the barbiturates. In Sweden, barbiturates http://z.umn.edu/INNOVATIONS 2012, Vol. 3, No. 3, Article 87 INNOVATIONS in pharmacy 2 Commentary POLICY such as amobarbital, hexobarbital, pentobarbital and Only 9% percent of drugs banned by the U.S.