| Revision as of 14:05, 6 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456979124 of page Sibutramine for the Chem/Drugbox validation project (updated: 'DrugBank'). |
Latest revision as of 06:27, 19 November 2024 edit Slothwizard (talk | contribs)Extended confirmed users1,346 editsm SNRI abbreviationTags: Visual edit Mobile edit Mobile web edit |
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{{Short description|Appetite suppressant}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Infobox drug |
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{{Drugbox |
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| Watchedfields = changed |
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| class = ]; ] |
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| verifiedrevid = 456482980 |
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| verifiedrevid = 464390010 |
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| IUPAC_name = (±)-dimethyl-1--''N,N'',3-trimethylbutan- 1-amine |
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| IUPAC_name = 1-(1-(4-chlorophenyl)cyclobutyl)-N,N,2,2-tetramethylpropan-1-amine |
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| image = Sibutramine.svg |
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| image = Sibutramine.svg |
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| width = 200px |
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| image2 = Sibutramine3d.png |
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| image2 = Sibutramine ball-and-stick model.png |
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| imagename = 1 : 1 mixture (racemate) |
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| width2 = 200px |
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| drug_name = Sibutramine |
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| caption = Sibutramine (top),<br />(''S'')-(−)-sibutramine (bottom) |
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<!--Clinical data--> |
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<!--Clinical data-->| tradename = Meridia, others |
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| tradename = Meridia |
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| Drugs.com = {{drugs.com|monograph|sibutramine-hydrochloride}} |
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| Drugs.com = {{drugs.com|monograph|sibutramine-hydrochloride}} |
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| MedlinePlus = a601110 |
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| MedlinePlus = a601110 |
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| pregnancy_US = C |
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| pregnancy_US = C |
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| pregnancy_category = No human data exists; inconclusive evidence of teratogenic potential in animal studies |
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| pregnancy_category = No human data exists; inconclusive evidence of teratogenic potential in animal studies |
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| legal_BR = B2 |
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| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=] |language=pt-BR |publication-date=2023-04-04}}</ref> |
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| legal_CA_comment = Withdrawn from market |
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| legal_US = Schedule IV |
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| legal_US = Schedule IV |
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| routes_of_administration = Oral |
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| routes_of_administration = ] |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data-->| bioavailability = Absorption 77%, considerable ] |
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| protein_bound = 97%, (94% for its desmethyl metabolites, M<sub>1</sub> & M<sub>2</sub>) |
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| bioavailability = Absorption 77%, considerable ] |
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| metabolism = ] (]-mediated) |
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| metabolism = ] (]-mediated) |
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| elimination_half-life = sibutramine approx. 1 hour</br>Metabolite 1: 14 hours</br>Metabolite 2: 16 hours |
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| elimination_half-life = 1 hour (sibutramine), 14 hours (M<sub>1</sub>) & 16 hours (M<sub>2</sub>) |
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| excretion = Biliary (sibutramine and active metabolites), ] (inactive metabolites) |
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| excretion = Urine (77%), feces (8%) |
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<!--Identifiers--> |
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<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|CAS}} |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 106650-56-0 |
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| CAS_number = 106650-56-0 |
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| CAS_supplemental = <br />{{CAS|766462-77-5}} (chlorosibutramine) |
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| ATC_prefix = A08 |
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| ATC_prefix = A08 |
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| ATC_suffix = AA10 |
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| ATC_suffix = AA10 |
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| PubChem = 5210 |
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| PubChem = 5210 |
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| IUPHAR_ligand = 2586 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB01105 |
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| DrugBank = DB01105 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 1419 |
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| ChEMBL = 1419 |
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| synonyms = BTS-54524 |
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<!--Chemical data--> |
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<!--Chemical data-->| C = 17 |
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| C=17 | H=26 | Cl=1 | N=1 |
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| H = 26 |
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| Cl = 1 |
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| molecular_weight = 279.85 g/mol |
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| N = 1 |
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| smiles = Clc1ccc(cc1)C2(C(N(C)C)CC(C)C)CCC2 |
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| SMILES = ClC1=CC=C(C2(CCC2)C(CC(C)C)N(C)C)C=C1 |
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| InChI = 1/C17H26ClN/c1-13(2)12-16(19(3)4)17(10-5-11-17)14-6-8-15(18)9-7-14/h6-9,13,16H,5,10-12H2,1-4H3 |
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| InChIKey = UNAANXDKBXWMLN-UHFFFAOYAP |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C17H26ClN/c1-13(2)12-16(19(3)4)17(10-5-11-17)14-6-8-15(18)9-7-14/h6-9,13,16H,5,10-12H2,1-4H3 |
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| StdInChI = 1S/C17H26ClN/c1-13(2)12-16(19(3)4)17(10-5-11-17)14-6-8-15(18)9-7-14/h6-9,13,16H,5,10-12H2,1-4H3 |
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| StdInChIKey = UNAANXDKBXWMLN-UHFFFAOYSA-N |
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| StdInChIKey = UNAANXDKBXWMLN-UHFFFAOYSA-N |
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}} |
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}} |
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'''Sibutramine''', formerly sold under the brand name '''Meridia''' among others, is an ] which has been discontinued in many countries. It works as a ] (SNRI) similar to certain ]. Until 2010, it was widely marketed and prescribed as an ] in the treatment of ] along with ] and ]. It has been associated with increased ]s and ] and has been ] from the market in 2010 in several countries and regions including |
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Australia,<ref>{{cite web |url = http://www.tga.gov.au/safety/alerts-medicine-sibutramine-101008.htm |title = Sibutramine (Reductil) - withdrawal in Australia |newspaper = Therapeutic Goods Administration (Tga) |year = 2010 |access-date = 2014-10-06 |publisher = Therapeutic Goods Administration, Department of Health, Australian Government |archive-date = 2014-07-03 |archive-url = https://web.archive.org/web/20140703045800/http://tga.gov.au/safety/alerts-medicine-sibutramine-101008.htm |url-status = dead }}</ref> Canada,<ref> {{Webarchive|url=https://web.archive.org/web/20130111132644/http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2010/meridia_hpc-cps-eng.php |date=2013-01-11 }}: Subject: Voluntary withdrawal of Meridia (sibutramine) capsules from the Canadian market.</ref> |
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China,<ref>{{cite web |url=http://www.sda.gov.cn/WS01/CL0195/55333.html |title=Notification of Termination of Production, Sale, and Usage of Sibutramine Preparations and Their Active Pharmaceutical Ingredient |publisher=sda.gov in People's Republic of China |date=October 30, 2010 |access-date=2011-05-21 |archive-date=2011-10-07 |archive-url=https://web.archive.org/web/20111007065924/http://www.sda.gov.cn/WS01/CL0195/55333.html |url-status=dead }}</ref> the European Union,<ref>{{in lang|de}} Sibutramin-Vertrieb in der Europäischen Union ausgesetzt {{Webarchive|url=https://archive.today/20120719155409/http://www.abbott.de/content/e17/e127/e15940/index_de.html|date=2012-07-19}}. ] in Germany. ] 2010-01-21. Retrieved 2010-01-27</ref> Hong Kong,<ref>{{cite press release |url=http://www.info.gov.hk/gia/general/201011/02/P201011020204.htm |title=De-registration of pharmaceutical products containing sibutramine |publisher=info.gov in Hong Kong |date=November 2, 2010 |access-date=2010-11-08}}</ref> India,<ref>{{cite press release |url=http://pib.nic.in/newsite/erelease.aspx?relid=70841 |title=Banned Medicines |publisher=Ministry of Health and Family Welfare |date=February 10, 2011 |access-date=2011-03-15}}</ref> Mexico, New Zealand,<ref>{{cite press release |url=http://www.medsafe.govt.nz/hot/media/2010/SibutramineOct2010.asp |title=Withdrawal of Sibutramine (Reductil) in New Zealand |publisher=MedSafe in New Zealand |date=October 11, 2010 |access-date=2012-11-06}}</ref> the Philippines,<ref>{{cite news|title=FDA warns online sellers of banned slimming pills|url=http://business.inquirer.net/159883/fda-warns-online-sellers-of-banned-slimming-pills|access-date=February 20, 2014|date=January 12, 2014|archive-date=January 15, 2014|archive-url=https://web.archive.org/web/20140115102854/http://business.inquirer.net/159883/fda-warns-online-sellers-of-banned-slimming-pills|url-status=live}}</ref> Thailand,<ref>{{cite press release |url=http://elib.fda.moph.go.th/fulltext2/word/41633/41633.pdf |title=Thai FDA reveals voluntary withdrawal of sibutramine from the Thai market |publisher=Food and Drug Administration of Thailand |date=October 20, 2010 |access-date=2010-12-22 |archive-date=2011-05-11 |archive-url=https://web.archive.org/web/20110511225841/http://elib.fda.moph.go.th/fulltext2/word/41633/41633.pdf |url-status=dead }}</ref> the United Kingdom,<ref>{{cite news |url=http://news.bbc.co.uk/1/hi/health/8473555.stm |title=Top obesity drug sibutramine being suspended |access-date=2010-01-22 |work=BBC News |date=2010-01-22 |archive-date=2010-01-25 |archive-url=https://web.archive.org/web/20100125005254/http://news.bbc.co.uk/1/hi/health/8473555.stm |url-status=live }}</ref> and the United States.<ref name="wsj">{{cite news|vauthors=Rockoff JD, Dooren JC|title=Abbott Pulls Diet Drug Meridia Off US Shelves|url=https://online.wsj.com/article/BT-CO-20101008-710904.html|access-date=8 October 2010|newspaper=The Wall Street Journal|date=October 8, 2010|archive-date=11 October 2010|archive-url=https://web.archive.org/web/20101011004015/http://online.wsj.com/article/BT-CO-20101008-710904.html|url-status=dead}}</ref> However, the drug remains available in some countries.<ref name="Drugs.com">{{cite web |url=https://www.drugs.com/international/sibutramine.html |title=Sibutramine - Drugs.com |website=drugs.com |access-date=2017-10-08 |archive-date=2017-10-08 |archive-url=https://web.archive.org/web/20171008180231/https://www.drugs.com/international/sibutramine.html |url-status=live }}</ref> |
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Sibutramine was originally developed in 1988 by ] in ], UK,<ref name="Buckett1988">{{cite journal | vauthors = Buckett WR, Thomas PC, Luscombe GP | title = The pharmacology of sibutramine hydrochloride (BTS 54 524), a new antidepressant which induces rapid noradrenergic down-regulation | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 12 | issue = 5 | pages = 575–584 | year = 1988 | pmid = 2851857 | doi = 10.1016/0278-5846(88)90003-6 | s2cid = 24787523 }}</ref> and manufactured and marketed by ] and sold under a variety of brand names including Reductil, Meridia, Siredia, and Sibutrex before its withdrawal 2010 from most markets. It was classified as a ] ] in the United States. |
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As of 2018, the U.S. ] (FDA) still found sibutramine in over 700 diet supplements marketed as "natural", "traditional", or "herbal remedies". |
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==Medical uses== |
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Sibutramine has been used to produce appetite suppression for the purpose of attaining ] in the treatment of patients with obesity. |
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==Contraindications== |
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Sibutramine is contraindicated in patients with: |
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* Psychiatric conditions as ], ], severe ], or pre-existing ] |
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* Patients with a history of or a predisposition to drug or alcohol ] |
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* ] to the drug or any of the inactive ingredients |
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* Patients below 18 and above 65 years of age<ref name="fda_August2010">{{cite web|url=https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm225956.htm|title=The FDA August 2010 drug safety update|website=fda.gov|access-date=2019-12-16|archive-date=2017-01-12|archive-url=https://web.archive.org/web/20170112175513/http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm225956.htm|url-status=live}}</ref> |
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* Concomitant treatment with a ] (MAOI), ], or other ] active drugs, particularly other ] |
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* History of ] |
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* ] that is not sufficiently controlled (e.g., >145/90 mmHg), caution in controlled hypertension |
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* Existing ] |
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* Existing damage on heart valves, ], previous ] (heart attack), ], ], or ] (e.g., ] or ] )<ref name="fda_August2010" /> |
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* ] (overactive thyroid gland) |
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* Closed-angle ] |
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* ] |
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* Enlargement of the ] gland with ] (relative contraindication) |
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* ] |
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* ] and ] women (relative contraindication) |
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==Side effects== |
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A higher number of ] has been observed in people taking sibutramine versus control (11.4% vs. 10.0%).<ref name = "FDA_Safety_Information">{{cite web |url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm191650.htm |title =Meridia (sibutramine hydrochloride): Follow-Up to an Early Communication about an Ongoing Safety Review | publisher = United States Food and Drug Administration | archive-url = https://web.archive.org/web/20120106041327/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm198221.htm | date = 1 February 2010 | archive-date = 6 January 2012 | url-status = dead }}</ref> In 2010, the FDA noted the concerns that sibutramine increases the risk of ] and ] in patients with a history of cardiovascular disease.<ref name = "FDA_Safety_Information" /> |
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Frequently encountered side effects include ], paradoxically ], ], ], ], ], ], ], ], ], ], ], or ]/]. |
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In a 2016 Cochrane review, sibutramine was found to substantially increase ] and heart rate in some patients, in the updated review in 2021 sibutramine was not included since the drug had been withdrawn from the market.<ref>{{cite journal | vauthors = Siebenhofer A, Winterholer S, Jeitler K, Horvath K, Berghold A, Krenn C, Semlitsch T | title = Long-term effects of weight-reducing drugs in people with hypertension | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD007654 | date = January 2021 | issue = 1 | pmid = 33454957 | pmc = 8094237 | doi = 10.1002/14651858.CD007654.pub5 }}</ref> When used, regular blood pressure monitoring needed to be performed. |
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The following side effects are infrequent but serious and require immediate medical attention: ]s, ], mental changes (e.g., excitement, restlessness, confusion, depression, rare thoughts of suicide). |
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Symptoms that require urgent medical attention are ]s, problems urinating, abnormal bruising or bleeding, ], ], ], fever and ]s, ], ], abnormal vision, ] and ]. |
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Currently, no case of ] has been noted. (Fenfluramine, of the 1990s "Fen-Phen" combo, forced excess release of neurotransmitters—a different action. Phentermine was uninvolved in the rare—but clinically significant—heart issues of fenfluramine.) |
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== Interactions == |
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Sibutramine has a number of clinically significant interactions. The concomitant use of sibutramine and ]s (MAOIs, such as ]) is not indicated, as it may increase the risk of ], a somewhat rare but serious ].<ref name="RxList">{{cite web |url = http://www.rxlist.com/cgi/generic/sibutramine_ad.htm |title = Meridia Side Effects, and Drug Interactions |year = 2007 |access-date = 2007-04-29 |publisher = RxList.com |archive-date = 2008-08-09 |archive-url = https://web.archive.org/web/20080809212950/http://www.rxlist.com/cgi/generic/sibutramine_ad.htm |url-status = dead }}</ref> Sibutramine should not be taken within two weeks of stopping or starting an MAOI. Taking both sibutramine and certain medications used in the treatment of ]s—such as ]s and ]s—as well as ]s, may also increase the risk for serotonin syndrome, as may the use of more than one serotonin reuptake inhibitor at the same time.<ref name="RxList"/> |
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The concomitant use of sibutramine and drugs which inhibit ], such as ] and ], may increase plasma levels of sibutramine.<ref>{{in lang|pt}} Cloridrato de sibutramina monoidratado. Bula. . Medley (2007).</ref> |
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Sibutramine does not affect the efficacy of ].<ref name="RxList"/> |
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==Pharmacology== |
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===Pharmacodynamics=== |
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{| class="wikitable floatright" |
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|+ Sibutramine (and metabolites)<ref name="pmid12119986">{{cite journal | vauthors = Nisoli E, Carruba MO | title = An assessment of the safety and efficacy of sibutramine, an anti-obesity drug with a novel mechanism of action | journal = Obesity Reviews | volume = 1 | issue = 2 | pages = 127–139 | date = October 2000 | pmid = 12119986 | doi = 10.1046/j.1467-789x.2000.00020.x | s2cid = 20553857 }}</ref><ref name="pmid19505264">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Serotonergic drugs and valvular heart disease | journal = Expert Opinion on Drug Safety | volume = 8 | issue = 3 | pages = 317–329 | date = May 2009 | pmid = 19505264 | pmc = 2695569 | doi = 10.1517/14740330902931524 }}</ref> |
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! Compound !! {{abbrlink|SERT|Serotonin transporter}} !! {{abbrlink|NET|Norepinephrine transporter}} !! {{abbrlink|DAT|Dopamine transporter}} |
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| Sibutramine || 298–2,800 || 350–5,451 || 943–1,200 |
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| ] || 15 || 20 || 49 |
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| ] || 44 || 4 || 12 |
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| ] || 9,200 || 870 || 180 |
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| ] || 20 || 15 || 45 |
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| ] || 140 || 13 || 8.9 |
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| ] || 4,300 || 62 || 12 |
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| colspan="4" | Values are K<sub>i</sub> (nM). |
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Sibutramine is a ] (SNRI) that, in humans, reduces the ] of ] (by ~73%), ] (by ~54%), and ] (by ~16%),<ref name = "PI">{{cite web|title=Meridia (sibutramine hydrochloride monohydrate) Capsules CIV. Full Prescribing Information|url=https://www.fda.gov/downloads/Drugs/DrugSafety/PublicHealthAdvisories/UCM130745.pdf|publisher=Abbott Laboratories, North Chicago, IL 60064, U.S.A.|access-date=6 February 2016|archive-date=17 February 2017|archive-url=https://web.archive.org/web/20170217195530/http://www.fda.gov/downloads/Drugs/DrugSafety/PublicHealthAdvisories/UCM130745.pdf|url-status=live}}</ref> thereby increasing the levels of these substances in ]s and helping enhance ]; the serotonergic action, in particular, is thought to influence appetite. Older ] agents such as ] and ] force the release of these neurotransmitters rather than affecting their reuptake.<ref name="Heal">{{cite journal | vauthors = Heal DJ, Aspley S, Prow MR, Jackson HC, Martin KF, Cheetham SC | title = Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from d-amphetamine and d-fenfluramine | journal = International Journal of Obesity and Related Metabolic Disorders | volume = 22 | issue = Suppl 1 | pages = S18-28; discussion S29 | date = August 1998 | pmid = 9758240 }}</ref> |
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Sibutramine's mechanism of action is similar to ]s, and it has demonstrated antidepressant effects in animal models of depression.<ref name="Buckett1988" /> It was approved by the U.S. ] (FDA) in November 1997<ref>{{cite press release |url=https://www.fda.gov/bbs/topics/ANSWERS/ANS00835.html |title = FDA APPROVES SIBUTRAMINE TO TREAT OBESITY |date = November 24, 1997 |publisher = U.S. ] |access-date = 2007-04-29}}</ref> for the treatment of obesity. |
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Sibutramine is reported to be a ] to two ]s, ] (M1; BTS-54354) and ] (M2; BTS-54505), with much greater potency as monoamine reuptake inhibitors.<ref name="KimSong2009">{{cite journal | vauthors = Kim KA, Song WK, Park JY | title = Association of CYP2B6, CYP3A5, and CYP2C19 genetic polymorphisms with sibutramine pharmacokinetics in healthy Korean subjects | journal = Clinical Pharmacology and Therapeutics | volume = 86 | issue = 5 | pages = 511–518 | date = November 2009 | pmid = 19693007 | doi = 10.1038/clpt.2009.145 | s2cid = 24789264 }}</ref><ref name="Hofbauer2004">{{cite book | vauthors = Hofbauer K | title=Pharmacotherapy of obesity : options and alternatives | publisher=CRC Press | location=Boca Raton, Fla | year=2004 | isbn=978-0-415-30321-7 }}</ref> Further studies have indicated that the (''R'')-enantiomers of each metabolite exert significantly stronger anorectic effects than the (''S'')-enantiomers.<ref>{{cite journal | vauthors = Glick SD, Haskew RE, Maisonneuve IM, Carlson JN, Jerussi TP | title = Enantioselective behavioral effects of sibutramine metabolites | journal = European Journal of Pharmacology | volume = 397 | issue = 1 | pages = 93–102 | date = May 2000 | pmid = 10844103 | doi = 10.1016/s0014-2999(00)00216-8 }}</ref> |
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Unlike other serotonergic appetite suppressants like ], sibutramine and its metabolites have only low and likely inconsequential ] for the ].<ref name = "PI" /> |
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===Pharmacokinetics=== |
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Sibutramine is well absorbed from the ] (77%), but undergoes considerable ], reducing its bioavailability. The drug itself reaches its peak ] level after 1 hour and has also a half-life of 1 hour. Sibutramine is metabolized by ] ] ] into two pharmacologically active primary and secondary ]s (called active metabolites 1 and 2) with half-lives of 14 and 16 hours, respectively. Peak plasma concentrations of active metabolites 1 and 2 are reached after three to four hours. The following metabolic pathway mainly results in two inactive conjugated and hydroxylated metabolites (called metabolites 5 and 6). Metabolites 5 and 6 are mainly excreted in the urine. |
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==Chemistry== |
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Sibutramine has usually been used in the form of the ] ] ]. |
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===Detection in body fluids=== |
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Sibutramine and its two active ''N''-demethylated metabolites may be measured in ]s by ]-]. Plasma levels of these three species are usually in the 1–10 ''μ''g/L range in persons undergoing therapy with the drug. The parent compound and ] are often not detectable in urine, but ] is generally present at concentrations of >200 ''μ''g/L.<ref name="pmid17072906">{{cite journal | vauthors = Jain DS, Subbaiah G, Sanyal M, Shrivastav PS, Pal U, Ghataliya S, Kakad A, Patel H, Shah S | display-authors = 6 | title = Liquid chromatography/electrospray ionization tandem mass spectrometry validated method for the simultaneous quantification of sibutramine and its primary and secondary amine metabolites in human plasma and its application to a bioequivalence study | journal = Rapid Communications in Mass Spectrometry | volume = 20 | issue = 23 | pages = 3509–3521 | date = 2006 | pmid = 17072906 | doi = 10.1002/rcm.2760 | bibcode = 2006RCMS...20.3509J }}</ref><ref name="pmid16723754">{{cite journal | vauthors = Thevis M, Sigmund G, Schiffer AK, Schänzer W | title = Determination of N-desmethyl- and N-bisdesmethyl metabolites of Sibutramine in doping control analysis using liquid chromatography-tandem mass spectrometry | journal = European Journal of Mass Spectrometry | location = Chichester, England | volume = 12 | issue = 2 | pages = 129–36 | date = 2006 | pmid = 16723754 | doi = 10.1255/ejms.797 | s2cid = 23359461 }}</ref><ref>{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, CA | date = 2008 | pages = 1426–1427 }}</ref> |
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==Society and culture== |
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===Regulatory approval, 1997–2010=== |
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Sibutramine was originally developed in 1988 by ] in ], UK,<ref name="Buckett1988"/>/ and marketed by ] after BASF/Knoll AG purchased the Boots Research Division in 1995. |
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It was classified as a ] ] in the United States. |
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In 1997, the US FDA approved it for weight loss and maintenance of weight loss in people with a BMI greater than or equal to 30 kg/m2 or for people with a BMI ≥27 kg/m2 who have other cardiovascular risk factors. It was manufactured and marketed by ]s.<ref name="fda1097">{{Cite web |author=Center for Drug Evaluation and Research |date=2019-06-28 |title=FDA Drug Safety Communication: FDA Recommends Against the Continued Use of Meridia (sibutramine) |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-recommends-against-continued-use-meridia-sibutramine |access-date=2022-12-12 |website=FDA |language=en |archive-date=2022-12-12 |archive-url=https://web.archive.org/web/20221212210836/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-recommends-against-continued-use-meridia-sibutramine |url-status=live }}</ref> |
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It was sold under a variety of brand names including Reductil, Meridia, Siredia, and Sibutrex. |
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In 2002, studies looked into reports of sudden death, heart failure, ] and gastrointestinal problems. Despite a 2002 petition by ]-founded NGO ],<ref>{{cite web |url = http://www.citizen.org/publications/print_release.cfm?ID=7160 |title = Petition to FDA to ban the diet drug sibutramine (MERIDIA) (HRG Publication #1613) |vauthors = Wolfe SM, Sasich LD, Barbehenn E |date = March 19, 2002 |access-date = 2007-04-29 |publisher = ] |archive-date = 2006-12-19 |archive-url = https://web.archive.org/web/20061219051817/http://www.citizen.org/publications/print_release.cfm?ID=7160 |url-status = live }}</ref> the FDA made no attempts to withdraw the drug, but was part of a Senate hearing in 2005.<ref>{{cite news | vauthors = Japsen B |title=FDA weighs decision on Meridia; Health advisory likely for Abbott obesity drug |publisher=]. Chicago, Illinois |date= 13 March 2005 |pages=1}}</ref> Similarly, in 2004, ], FDA "whistleblower", testified before a ] hearing that sibutramine may be more dangerous than the conditions it is used for.<ref>Hearing of 17 November 2004. {{cite web | title = Insider: FDA Won't Protect Public | work = CBS News | url = https://www.cbsnews.com/news/insider-fda-wont-protect-public/ | archive-url = https://web.archive.org/web/20060519170603/http://www.cbsnews.com/stories/2004/12/07/health/main659529.shtml | archive-date = 19 May 2006 | url-status = live | date = 19 November 2004 }}</ref> |
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Between January 2003 and November 2005, a large randomized-controlled "Sibutramine Cardiovascular OUTcomes" (SCOUT) study with 10,742 patients examined whether or not sibutramine administered within a weight management program reduces the risk for cardiovascular complications in people at high risk for heart disease and concluded that use of silbutramine had a RR 1.16 for the primary outcome (composit of nonfatal MI, nonfatal CVA, cardiac arrest, and CV death).<ref name="pmid20818901">{{cite journal | vauthors = James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, Renz CL | display-authors = 6 | title = Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects | journal = The New England Journal of Medicine | volume = 363 | issue = 10 | pages = 905–917 | date = September 2010 | pmid = 20818901 | doi = 10.1056/NEJMoa1003114 | hdl-access = free | hdl = 2437/111825 | url = https://espace.library.uq.edu.au/view/UQ:382403/UQ382403_OA.pdf }}</ref> |
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In April 2010 ] (chairman of the ]) said in a dissenting article, "Sibutramine: gone, but not forgotten", that the SCOUT study was flawed as it only covered high-risk patients and did not consider obese patients who did not have cardiovascular complications or similar contraindications.<ref>{{cite journal | vauthors = Haslam D | title = Sibutramine: gone, but not forgotten | journal = Pract Diab Int | date = April 2010 | volume = 27 | issue = 3 | pages = 96–97 | url = http://www.practicaldiabetesinternational.com/SpringboardWebApp/userfiles/espdi/file/Ldr%20Haslam_Layout%201.pdf | archive-url = https://web.archive.org/web/20150726041800/http://www.practicaldiabetes.com/SpringboardWebApp/userfiles/espdi/file/Ldr%20Haslam_Layout%201.pdf | archive-date = 26 July 2015 | doi = 10.1002/pdi.1453 }}</ref> |
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On January 21, 2010, the ] recommended suspension of marketing authorizations for sibutramine based on the SCOUT study results.<ref>{{cite web | title = European Medicines Agency recommends suspension of marketing authorisations for sibutramine | url = http://www.ema.europa.eu/pdfs/human/referral/sibutramine/3940810en.pdf | archive-url = https://web.archive.org/web/20100401084541/http://www.ema.europa.eu/pdfs/human/referral/sibutramine/3940810en.pdf | archive-date = 2010-04-01 | url-status = dead | publisher = European Medicines Agency | date = January 21, 2010}}</ref> |
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In August 2010 the FDA added a new contraindication for patients over 65 years of age because clinical studies of sibutramine did not include sufficient numbers of such patients.<ref name="fda_August2010" /> |
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On October 8, 2010, the FDA recommended against continued prescribing because of unnecessary cardiovascular risks to patients, asking ] to voluntarily withdraw.<ref name="fda1097"/> Abbott announced the same day that it was withdrawing sibutramine from the US market, citing concerns over minimal efficacy coupled with increased risk of adverse cardiovascular events.<ref>{{cite news | url=https://www.nytimes.com/2010/10/09/health/09drug.html?ref=business | work=The New York Times | author=Andrew Pollack | title=Abbott Labs Withdraws Meridia From Market | date=October 8, 2010 | access-date=February 25, 2017 | archive-date=March 28, 2017 | archive-url=https://web.archive.org/web/20170328105839/http://www.nytimes.com/2010/10/09/health/09drug.html?ref=business | url-status=live }}</ref> |
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===Counterfeit weight-loss products, 2008–present=== |
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On December 22, 2008, the United States ] issued an alert to consumers naming 27 different products marketed as “]s” for weight loss, that illegally contain undisclosed amounts of sibutramine.<ref>{{cite press release|url=https://www.fda.gov/bbs/topics/NEWS/2008/NEW01933.html |publisher=U.S. Food and Drug Administration |title=FDA warns consumers about tainted weight loss pills |date=22 December 2008}}</ref><ref>{{cite web |url=https://www.fda.gov/cder/consumerinfo/weight_loss_products.htm |publisher=U.S. Food and Drug Administration Center for Drug Evaluation and Research |title=Consumer directed questions and answers about FDA's initiative against contaminated weight loss products |date=22 December 2008 |access-date=16 December 2019 |archive-date=17 March 2009 |archive-url=https://web.archive.org/web/20090317054247/https://www.fda.gov/cder/consumerinfo/weight_loss_products.htm |url-status=live }}</ref> In March 2009, Dieter Müller ''et al.'' published a study of sibutramine poisoning cases from similar Chinese "]s" sold in Europe, containing as much as twice the dosage of the legally licensed drug.<ref>{{cite journal | vauthors = Müller D, Weinmann W, Hermanns-Clausen M | title = Chinese slimming capsules containing sibutramine sold over the Internet: a case series | journal = Deutsches Ärzteblatt International | volume = 106 | issue = 13 | pages = 218–222 | date = March 2009 | pmid = 19471631 | pmc = 2680571 | doi = 10.3238/arztebl.2009.0218 }}</ref> |
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An additional 34 products were recalled by the FDA on April 22, 2009, further underscoring the risks associated with unregulated "herbal supplements" to unsuspecting persons. This concern is especially relevant to those with underlying medical conditions incompatible with undeclared pharmaceutical adulterants.<ref> {{Webarchive|url=https://web.archive.org/web/20090426072205/http://www.webmd.com/diet/news/20090422/34-weight-loss-products-recalled |date=2009-04-26 }}, ], 22 April 2009.</ref> In January 2010, a similar alert was issued for counterfeit versions of the ] weight loss drug Alli sold over the Internet. Instead of the active ingredient ], the counterfeit drugs contain sibutramine, and at concentrations at least twice the amount recommended for weight loss.<ref>{{cite news |publisher= ] |url= http://www.cnn.com/2010/HEALTH/01/23/fake.diet.drug/index.html |title= Fake Alli diet pills can pose health risks |access-date= 2010-01-24 |date= January 23, 2010 |archive-date= 2010-01-25 |archive-url= https://web.archive.org/web/20100125215740/http://www.cnn.com/2010/HEALTH/01/23/fake.diet.drug/index.html |url-status= live }}</ref> |
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In March 2010 ] advised the public that illegal "Herbal Diet Natural" had been found on the market, containing sibutramine, which is a prescription drug in Canada, without listing sibutramine as an ingredient.<ref>{{cite news | title=Herbal diet product poses heart risk | date=March 26, 2010 | publisher=CBC News | url=https://www.cbc.ca/news/science/herbal-diet-product-poses-heart-risk-1.963692 | access-date=March 26, 2010 | archive-date=March 28, 2010 | archive-url=https://web.archive.org/web/20100328234323/http://www.cbc.ca/health/story/2010/03/26/herbal-dietnatural.html | url-status=live }}</ref> In October 2010 FDA notified consumers that "Slimming Beauty Bitter Orange Slimming Capsules contain the active pharmaceutical ingredient sibutramine, a prescription-only drug which is a stimulant. Sibutramine is not listed on the product label."<ref>{{cite web|url=https://www.drugs.com/fda/slimming-beauty-bitter-orange-slimming-capsules-undeclared-ingredient-12830.html#ixzz126K59G3L|title=FDA Alert: Slimming Beauty Bitter Orange Slimming Capsules: Undeclared Drug Ingredient|website=drugs.com|access-date=2018-01-23|archive-date=2018-08-25|archive-url=https://web.archive.org/web/20180825074051/https://www.drugs.com/fda/slimming-beauty-bitter-orange-slimming-capsules-undeclared-ingredient-12830.html#ixzz126K59G3L|url-status=live}}</ref> |
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In October 2010 the ] in the UK issued a warning regarding "Payouji tea" and "Pai You Guo Slim Capsules" which were found to contain undeclared quantities of sibutramine.<ref>{{cite web | title = Press release: Warning over unlicensed herbal Payouji tea and Pai You Guo Slim Capsules | url = http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON096957 | archive-url = https://web.archive.org/web/20120209133658/http://www.mhra.gov.uk/NewsCentre/Pressreleases/CON096957 | archive-date = 9 February 2012 | date = 20 October 2010 | work = United Kingdom Medicines & Healthcare Products Regulatory Agency }}</ref> |
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On December 30, 2010, the FDA released a warning regarding "Fruta Planta" dietary products, which were found to contain undeclared amounts of sibutramine. The recall stated that "there is NO SAFE formula on the US market and that all versions of Fruta Planta contain sibutramine. All versions of the formula are UNSAFE and should not be purchased from any source."<ref>{{cite web | title = PRock Marketing, LLC Issues a Voluntary Nationwide Recall of All weight loss formulas and variation of formulas of Reduce Weight Fruta Planta/Reduce Weight Dietary Supplement. | url = https://www.fda.gov/Safety/Recalls/ucm238495.htm | archive-url = https://web.archive.org/web/20120323065237/https://www.fda.gov/Safety/Recalls/ucm238495.htm | archive-date = 23 March 2012 | publisher = United States Food and Drug Administration }}</ref> |
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In 2011, some illegal weight loss products imported into Ireland have been found to contain sibutramine.<ref>{{cite news | url=http://www.irishtimes.com/newspaper/breaking/2011/0325/breaking18.html | newspaper=The Irish Times | vauthors=Pope C | title=Seizures of illegal medicines rise | access-date=2011-03-25 | archive-date=2012-10-24 | archive-url=https://web.archive.org/web/20121024044333/http://www.irishtimes.com/newspaper/breaking/2011/0325/breaking18.html | url-status=live }}</ref><ref>{{cite web|url=https://www.drugs.com/fda/slim-xtreme-herbal-slimming-capsule-undeclared-ingredient-12959.html|title=FDA Alert: Slim Xtreme Herbal Slimming Capsule: Undeclared Drug Ingredient|website=drugs.com|access-date=2018-01-23|archive-date=2018-08-25|archive-url=https://web.archive.org/web/20180825074258/https://www.drugs.com/fda/slim-xtreme-herbal-slimming-capsule-undeclared-ingredient-12959.html|url-status=live}}</ref> In 2012, similar concerns were raised in Australia, where illegal imported supplements have been found to contain sibutramine, resulting in public alerts from Australia's ].<ref>{{cite web | title = Majestic slimming capsules: Safety advisory | date = 9 November 2012 | url = http://www.tga.gov.au/safety/alerts-medicine-majestic-slimming-capsules-121109.htm | work = Therapeutic Goods Administration | publisher = Australian Government | access-date = 22 November 2012 | archive-date = 3 July 2014 | archive-url = https://web.archive.org/web/20140703030142/http://tga.gov.au/safety/alerts-medicine-majestic-slimming-capsules-121109.htm | url-status = dead }}</ref> |
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In October 2011, the FDA warned that 20 brands of dietary supplements were tainted with sibutramine.<ref>{{cite web | url = http://vitals.msnbc.msn.com/_news/2011/10/19/8402061-natural-diet-pills-tainted-with-banned-prescription-drug | archive-url = https://web.archive.org/web/20120111134200/http://vitals.msnbc.msn.com/_news/2011/10/19/8402061-natural-diet-pills-tainted-with-banned-prescription-drug | archive-date = 11 January 2012 | title = 'Natural' diet pills tainted with banned prescription drug | vauthors = Carroll L | work = ] | date = 19 October 2011 }}</ref> |
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In a 2018 study the FDA found synthetic additives including sibutramine in over 700 diet supplements marketed as "natural", "traditional" or "herbal remedies".<ref>{{Cite web|url=https://www.npr.org/sections/health-shots/2018/10/12/656875443/no-wonder-it-works-so-well-there-may-be-viagra-in-that-herbal-supplement|title=No Wonder It Works So Well: There May Be Viagra In That Herbal Supplement|website=NPR.org|date=12 October 2018|language=en|access-date=2018-10-14|vauthors=Cohen R|archive-date=2018-10-13|archive-url=https://web.archive.org/web/20181013010847/https://www.npr.org/sections/health-shots/2018/10/12/656875443/no-wonder-it-works-so-well-there-may-be-viagra-in-that-herbal-supplement|url-status=live}}</ref> |
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== References == |
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{{Reflist|2}} |
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== External links == |
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* {{Webarchive|url=https://web.archive.org/web/20110927063744/http://www.abbott.com/global/url/pressRelease/en_US/60.5:5/Press_Release_0908.htm |date=2011-09-27 }} |
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* from '']''. Includes dosage information and a comprehensive list of international brand names |
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* |
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{{Anorectics}} |
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{{Antidepressants}} |
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{{Monoamine reuptake inhibitors}} |
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{{Phenethylamines}} |
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