Orlistat: Difference between revisions
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{{Short description|Drug designed to treat obesity}} |
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{{drugbox |
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{{Use dmy dates|date=November 2020}} |
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| Verifiedfields = changed |
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{{Infobox drug |
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| verifiedrevid = 400837534 |
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| Verifiedfields = changed |
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| IUPAC_name = [(1''S'')-1-[(2''S'',3''S'')-3-hexyl-4-oxo-oxetan-2-yl]methyl]dodecyl] (2''S'')-2-formamido-4-methyl-pentanoate |
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| Watchedfields = changed |
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| image = Orlistat.svg |
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| verifiedrevid = 408353644 |
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| image2 = Orlistat 3D sticks.png |
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| image = Orlistat structure.svg |
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| width = 240 |
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| width = 300 |
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| InChI = 1/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1 |
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| alt = |
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| InChIKey = AHLBNYSZXLDEJQ-FWEHEUNIBY |
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| image2 = Orlistat ball-and-stick model.png |
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| smiles = O=C(O[C@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)CCCCCCCCCCC)[C@@H](NC=O)CC(C)C |
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| width2 = 300 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| alt2 = |
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| StdInChI = 1S/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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<!-- Clinical data --> |
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| StdInChIKey = AHLBNYSZXLDEJQ-FWEHEUNISA-N |
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| pronounce = |
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| CAS_number = 96829-58-2 |
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| tradename = Xenical, Alli |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| Drugs.com = {{drugs.com|monograph|orlistat}} |
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| ChEMBL = 175247 |
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| MedlinePlus = a601244 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| licence_EU = yes |
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| ChemSpiderID = 2298564 |
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| DailyMedID = Orlistat |
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| ATC_prefix = A08 |
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| licence_US = Orlistat |
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| ATC_suffix = AB01 |
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| pregnancy_AU = B1 |
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| ATC_supplemental = |
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| pregnancy_AU_comment = |
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| PubChem = 3034010 |
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| pregnancy_category = |
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| DrugBank = APRD00255 |
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| routes_of_administration = [[Oral administration|By mouth]] |
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| KEGG_Ref = {{keggcite|changed|kegg}} |
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| class = |
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| KEGG = D04028 |
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| |
| ATC_prefix = A08 |
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| ATC_suffix = AB01 |
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| molecular_weight = 495.735 g/mol |
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| ATC_supplemental = |
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| bioavailability = Negligible<ref>{{cite journal |author=Zhi J, Melia AT, Eggers H, Joly R, Patel IH |title=Review of limited systemic absorption of orlistat, a lipase inhibitor, in healthy human volunteers |journal=J Clin Pharmacol |volume=35 |issue=11 |pages=1103–8 |year=1995 |pmid=8626884 |doi=}}</ref> |
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| protein_bound = >99% |
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<!-- Legal status --> |
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| metabolism = In the [[Gastrointestinal tract|GI tract]] |
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| legal_AU = S3 |
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| legal_AU_comment = |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_BR_comment = |
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| legal_CA = Rx-only |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = P |
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| legal_UK_comment = / POM<ref name="Xenical SmPC">{{cite web | title=Xenical 120 mg hard capsules - Summary of Product Characteristics (SmPC) | website=(emc) | date=18 May 2017 | url=https://www.medicines.org.uk/emc/product/2592/smpc | access-date=19 September 2022 | archive-date=8 March 2022 | archive-url=https://web.archive.org/web/20220308043718/https://www.medicines.org.uk/emc/product/2592/smpc | url-status=live }}</ref><ref name="Beacita SmPC">{{cite web | title=Beacita 120mg Capsules, hard - Summary of Product Characteristics (SmPC) | website=(emc) | date=11 November 2020 | url=https://www.medicines.org.uk/emc/product/2934/smpc | access-date=19 September 2022 | archive-date=1 July 2022 | archive-url=https://web.archive.org/web/20220701231935/https://www.medicines.org.uk/emc/product/2934/smpc | url-status=live }}</ref><ref name="Alli SmPC">{{cite web | title=alli 60 mg hard capsules - Summary of Product Characteristics (SmPC) | website=(emc) | date=11 June 2021 | url=https://www.medicines.org.uk/emc/product/6533/smpc | access-date=19 September 2022 | archive-date=18 January 2022 | archive-url=https://web.archive.org/web/20220118225325/https://www2.medicines.org.uk/emc/product/6533/smpc | url-status=live }}</ref> |
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| legal_US = OTC |
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| legal_US_comment = / Rx-only<ref name="Xenical FDA label">{{cite web | title=Xenical- orlistat capsule | website=DailyMed | date=9 December 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6240792b-9224-2d10-e053-2a91aa0a2c3e | access-date=19 September 2022 | archive-date=17 July 2022 | archive-url=https://web.archive.org/web/20220717130355/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6240792b-9224-2d10-e053-2a91aa0a2c3e | url-status=live }}</ref><ref name="Alli FDA label">{{cite web | title=Alli- orlistat capsule | website=DailyMed | date=9 November 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f | access-date=19 September 2022 | archive-date=30 November 2021 | archive-url=https://web.archive.org/web/20211130041115/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2d3bd73-f3af-4ea5-a57c-66b0004cfe4f | url-status=live }}</ref> |
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| legal_EU = OTC |
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| legal_EU_comment = / Rx-only<ref name="Xenical EPAR">{{cite web | title=Xenical EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/xenical | access-date=20 September 2022 | archive-date=15 April 2021 | archive-url=https://web.archive.org/web/20210415115121/https://www.ema.europa.eu/en/medicines/human/EPAR/xenical | url-status=live }}</ref><ref name="Alli EPAR">{{cite web | title=Alli EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/alli | access-date=20 September 2022 | archive-date=23 January 2022 | archive-url=https://web.archive.org/web/20220123230458/https://www.ema.europa.eu/en/medicines/human/EPAR/alli | url-status=live }}</ref> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = Negligible<ref>{{cite journal | vauthors = Zhi J, Melia AT, Eggers H, Joly R, Patel IH | title = Review of limited systemic absorption of orlistat, a lipase inhibitor, in healthy human volunteers | journal = Journal of Clinical Pharmacology | volume = 35 | issue = 11 | pages = 1103–1108 | date = November 1995 | pmid = 8626884 | doi = 10.1002/j.1552-4604.1995.tb04034.x | s2cid = 23618845 }}</ref> |
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| protein_bound = >99% |
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| metabolism = In the [[Gastrointestinal tract|GI tract]] |
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| metabolites = |
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| onset = |
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| elimination_half-life = 1 to 2 hours |
| elimination_half-life = 1 to 2 hours |
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| duration_of_action = |
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| excretion = Fecal |
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| excretion = Fecal |
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| pregnancy_AU = B1 |
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| pregnancy_US = B |
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<!-- Identifiers --> |
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| licence_EU = Xenical |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| licence_US = Orlistat |
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| CAS_number = 96829-58-2 |
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| legal_AU = S3 |
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| |
| CAS_supplemental = |
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| PubChem = 3034010 |
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| legal_US = OTC |
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| IUPHAR_ligand = 5277 |
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| routes_of_administration = Oral |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank = DB01083 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 2298564 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = 95M8R751W8 |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D04028 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 94686 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 175247 |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| synonyms = tetrahydrolipstatin |
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<!-- Chemical and physical data --> |
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| IUPAC_name = (''S'')-((''S'')-1-((2''S'',3''S'')-3-Hexyl-4-oxooxetan-2-yl)tridecan-2-yl) 2-formamido-4-methylpentanoate |
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| C = 29 |
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| H = 53 |
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| N = 1 |
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| O = 5 |
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| SMILES = O=C(O[C@H](C[C@@H]1OC(=O)[C@H]1CCCCCC)CCCCCCCCCCC)[C@@H](NC=O)CC(C)C |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1 |
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| StdInChI_comment = |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = AHLBNYSZXLDEJQ-FWEHEUNISA-N |
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| density = |
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| density_notes = |
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| melting_point = |
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| melting_high = |
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| melting_notes = |
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| boiling_point = |
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| boiling_notes = |
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| solubility = |
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| sol_units = |
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| specific_rotation = |
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}} |
}} |
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'''Orlistat''' (marketed as a [[prescription drug|prescription]] under the trade name '''Xenical''' by [[Hoffmann–La Roche|Roche]] in most countries, or [[over-the-counter drug|over-the-counter]] as '''Alli'''<ref>Stylized with a lowercase ''a'' on the packaging (that is, "alli"), but capitalized conventionally in the manual.</ref> by [[GlaxoSmithKline]] in the [[United Kingdom]] and the [[United States]]), also known as '''tetrahydrolipstatin''', is a drug designed to treat [[obesity]].<ref name="TotalSynth">{{cite journal | author = Bodkin J, Humphries E, McLeod M | title = The total synthesis of (−)-tetrahydrolipstatin | journal = [[Australian Journal of Chemistry]] | volume = 56 | issue = 8 | pages = 795–803 | year = 2003 | doi = 10.1071/CH03121}}</ref> Its primary function is preventing the absorption of fats from the human diet, thereby reducing [[calorie|caloric]] intake. It is intended for use in conjunction with a physician-supervised [[dieting|reduced-calorie diet]]. Orlistat is the [[saturation (chemistry)|saturated]] derivative of [[lipstatin]], a potent [[natural product|natural]] inhibitor of [[pancreatic lipase]]s isolated from the [[bacteria|bacterium]] ''[[Streptomyces toxytricini]]''.<ref name="OriginalSynth">{{cite journal | author = Barbier P, Schneider F | title = Syntheses of tetrahydrolipstatin and absolute configuration of tetrahydrolipstatin and lipstatin | journal = Helvetica Chimica Acta | volume = 70 | issue = 1 | pages = 196–202 | year = 1987 | doi = 10.1002/hlca.19870700124}}</ref> However, due to simplicity and stability, orlistat rather than lipstatin was developed into an anti-obesity drug.<ref name="LipstatinSynth">{{cite journal | author = Pommier A, Pons M, Kocienski P| title = The first total synthesis of (-)-lipstatin | journal = [[Journal of Organic Chemistry]] | volume = 60 | issue = 22 | pages = 7334–7339 | year = 1995 | doi = 10.1021/jo00127a045}}</ref> |
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'''Orlistat''', sold under the brand name '''Xenical''' among others, is a [[medication]] used to treat [[obesity]]. Its primary function is preventing the absorption of fats from the human diet by acting as a [[Lipase inhibitors|lipase inhibitor]], thereby reducing [[calorie|caloric]] intake. It is intended for use in conjunction with a healthcare provider-supervised [[dieting|reduced-calorie diet]].<ref name="Xenical FDA label"/> |
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The effectiveness of orlistat in promoting [[weight loss]] is definite, though modest. Pooled data from [[clinical trial]]s suggest that people given orlistat in addition to lifestyle modifications, such as diet and exercise, lose about {{convert|2|-|3|kg|lb}} more than those not taking the drug over the course of a year.<ref name=Padwal>{{cite journal |author=Padwal R, Li SK, Lau DC |title=Long-term pharmacotherapy for obesity and overweight |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD004094 |year=2004 |pmid=15266516 |doi=10.1002/14651858.CD004094.pub2}}</ref> Orlistat also modestly reduces [[blood pressure]], and appears to prevent the onset of [[type 2 diabetes]], whether due to weight loss itself or to other effects; in a large [[randomized controlled trial]], orlistat was found to reduce the incidence of diabetes by nearly 40% in obese people.<ref name=XENDOS/> |
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Orlistat is the [[Saturated and unsaturated compounds|saturated]] derivative of [[lipstatin]], a potent [[natural product|natural]] inhibitor of [[pancreatic lipase]]s isolated from the [[bacteria|bacterium]] ''[[Streptomyces toxytricini]]''.<ref name="OriginalSynth">{{cite journal |vauthors=Barbier P, Schneider F | title = Syntheses of tetrahydrolipstatin and absolute configuration of tetrahydrolipstatin and lipstatin | journal = Helvetica Chimica Acta | volume = 70 | issue = 1 | pages = 196–202 | year = 1987 | doi = 10.1002/hlca.19870700124}}</ref> However, due to its relative simplicity and stability, orlistat was chosen over lipstatin for development as an [[Anti-obesity medication|anti-obesity drug]].<ref name="LipstatinSynth">{{cite journal |vauthors=Pommier A, Pons M, Kocienski P | title = The first total synthesis of (−)-lipstatin | journal = [[Journal of Organic Chemistry]] | volume = 60 | issue = 22 | pages = 7334–7339 | year = 1995 | doi = 10.1021/jo00127a045}}</ref> |
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Orlistat is notorious for its gastrointestinal [[adverse drug reaction|side effect]]s (sometimes referred to as ''treatment effects''), which can include [[steatorrhea]] (oily, loose stools). These decrease with time, however, and are the most frequently reported adverse effects of the drug. In the United States, the European Union, and Australia, orlistat is available for sale [[over-the-counter drug|without a prescription]]. Over-the-counter approval was controversial in the United States, with [[consumer organization|consumer advocacy]] group [[Public Citizen]] repeatedly opposing it on safety and efficacy grounds.<ref name="WP2"/> [[Generic drug|Generic]]s of orlistat are available in India. |
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The effectiveness of orlistat in promoting [[weight loss]] is definite but modest. Pooled data from [[clinical trial]]s suggest that people given orlistat in addition to lifestyle modifications, such as diet and exercise, lose about {{convert|2|-|3|kg|lb|0}} more than those not taking the drug over the course of a year.<ref name=Padwal>{{cite journal | vauthors = Padwal R, Li SK, Lau DC | title = Long-term pharmacotherapy for obesity and overweight | journal = The Cochrane Database of Systematic Reviews | volume = 2003 | issue = 3 | pages = CD004094 | year = 2004 | pmid = 15266516 | pmc = 8078201 | doi = 10.1002/14651858.CD004094.pub2 | veditors = Padwal RS }}</ref> Orlistat also modestly reduces [[blood pressure]] and appears to prevent the onset of [[type 2 diabetes]], whether from the weight loss itself or other effects. It reduces the incidence of diabetes type II in people who are obese around the same amount that lifestyle changes do.<ref name=BMJ2007>{{cite journal | vauthors = Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, Khunti K | title = Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis | journal = BMJ | volume = 334 | issue = 7588 | pages = 299 | date = February 2007 | pmid = 17237299 | pmc = 1796695 | doi = 10.1136/bmj.39063.689375.55 | name-list-style = vanc }}</ref> |
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==Pharmacology== |
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Orlistat works by inhibiting gastric and pancreatic [[lipases]], the [[enzyme]]s that break down [[triglycerides]] in the [[intestine]]. When lipase activity is blocked, triglycerides from the diet are not [[hydrolysis|hydrolyzed]] into absorbable free [[fatty acid]]s, and are excreted undigested instead. Only trace amounts of orlistat are absorbed systemically; the primary effect is local lipase inhibition within the [[gastrointestinal tract|GI tract]] after an oral dose. The primary route of elimination is through the [[feces]]. |
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Benefits aside, however, orlistat is noted for its gastrointestinal [[adverse drug reaction|side effects]] (sometimes referred to as ''treatment effects''), which can include [[steatorrhea]] (oily, loose stools). They decrease with time, however, and are the most frequently reported adverse effects of the drug.<ref name="Xenical FDA label" /> In Australia, the United States and the European Union, orlistat is available for sale [[over-the-counter drug|without a prescription]].<ref>{{cite web|title=POISONS STANDARD JUNE 2017|date=June 2017|access-date=18 August 2017|website=Federal Register of Legislation|publisher=Therapeutic Goods Administration|url=https://www.legislation.gov.au/Details/F2017L00605|archive-date=13 December 2020|archive-url=https://web.archive.org/web/20201213060305/https://www.legislation.gov.au/Details/F2017L00605/|url-status=live}}</ref> Over-the-counter approval was controversial in the United States, with [[consumer organization|consumer advocacy]] group [[Public Citizen]] repeatedly opposing it on safety and efficacy grounds.<ref name="WP2" /> [[Generic drug|Generic]] formulations of orlistat are available in some countries. In Australia it has been listed as an S3 medication, available from a pharmacist without a prescription, since 2000.<ref name=TGAauth/> |
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At the standard prescription dose of 120 [[milligram|mg]] three times daily before meals, orlistat prevents approximately 30% of dietary fat from being absorbed,<ref name="PDR">{{cite book |title= 2006 Physicians' Desk Reference (PDR) |year= 2006 |publisher= Thomson PDR |isbn= 1-56363-527-5}}</ref> and about 25% at the standard over-the-counter dose of 60 mg.<ref>{{cite web | url = http://www.myalli.com/whatisalli/commonquestions.aspx | title = myalli.com – frequently asked questions | year = 2007 | accessdate = 2007-08-18 | publisher = [[GlaxoSmithKline]] |archiveurl = http://web.archive.org/web/20070712125349/http://www.myalli.com/whatisalli/commonquestions.aspx <!-- Bot retrieved archive --> |archivedate = 2007-07-12}}</ref><ref>Parker-Pope, Tara. "[http://online.wsj.com/article/SB118220650299739698.html Weighing the Pros and Cons Of New Fat-Blocking Drug Alli]", ''[[The Wall Street Journal]]'', June 19, 2007, pp. D1. Retrieved on 2007-08-18.</ref> Higher doses do not produce more potent effects.<ref name="RxList">{{cite web | url = http://www.rxlist.com/cgi/generic/orlistat_cp.htm | title = Xenical Pharmacology, Pharmacokinetics, Studies, Metabolism | year = 2007 | accessdate = 2007-03-16 | publisher = RxList.com}}</ref> |
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{{TOC limit|3}} |
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== |
== Medical uses == |
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The amount of weight loss achieved with orlistat varies. In one-year [[clinical trial]]s, between 35.5% and 54.8% of subjects achieved a 5% or greater decrease in body mass, although not all of this mass was necessarily fat. Between 16.4% and 24.8% achieved at least a 10% decrease in body |
Orlistat is used for the treatment of [[obesity]]. The amount of weight loss achieved with orlistat varies. In one-year [[clinical trial]]s, between 35.5% and 54.8% of subjects achieved a 5% or greater decrease in body mass, although not all of this mass was necessarily fat. Between 16.4% and 24.8% achieved at least a 10% decrease in body fat.<ref name="Xenical FDA label" /> After orlistat was stopped, a [[statistical significance|significant]] number of subjects regained weight—up to 35% of the weight they had lost.<ref name="Xenical FDA label" /> It reduces the incidence of diabetes type II in people who are obese around the same amount that lifestyle changes do.<ref name=BMJ2007/> Long-term use of orlistat also leads to a very modest reduction in [[blood pressure]] (mean reductions of 2.5 and 1.9 [[mmHg]] in [[Systole (medicine)|systolic]] and [[diastole|diastolic]] blood pressure respectively).<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 | issue = 1 | pages = CD007654 | date = January 2021 | pmid = 33454957 | pmc = 8094237 | doi = 10.1002/14651858.CD007654.pub5 }}</ref> |
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== Contraindications == |
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The incidence of [[diabetes mellitus type 2|type 2 diabetes]] in an obese population over four years is decreased with orlistat (6.2%) compared to placebo (9.0%).<ref name="XENDOS">{{cite journal | author = Torgerson J, Hauptman J, Boldrin M, Sjöström L | title = XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients | journal = Diabetes Care | volume = 27 | issue = 1 | pages = 155–61 | year = 2004 | pmid = 14693982 | url = http://care.diabetesjournals.org/cgi/content/full/27/1/155 | doi = 10.2337/diacare.27.1.155}}</ref> Long-term use of orlistat also leads to a modest reduction in [[blood pressure]] (mean reductions of 2.5 and 1.9 [[mmHg]] in [[Systole (medicine)|systolic]] and [[diastole|diastolic]] blood pressure respectively).<ref>{{cite journal |author=Siebenhofer A, Horvath K, Jeitler K, ''et al.'' |title=Long-term effects of weight-reducing drugs in hypertensive patients |journal=Cochrane Database Syst Rev |volume=8 |issue=3 |year=2009 |month=July |pages=CD007654 |pmid=19588440 |doi=10.1002/14651858.CD007654.pub2}}</ref> |
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Orlistat is [[Contraindication|contraindicated]] in:<ref name="Xenical FDA label" /> |
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* [[Malabsorption]] |
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* Hypersensitivity to orlistat |
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* Reduced [[gallbladder]] function (e.g. after [[cholecystectomy]]) |
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* [[Pregnancy]] and [[breastfeeding]] |
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* [[Anorexia]] and [[Bulimia]] |
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* Use caution with: obstructed [[bile duct]], impaired liver function, and [[pancreatic disease]] |
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<!-- * Certain [[kidney]] problems --> |
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==Side effects== |
== Side effects == |
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The primary [[adverse drug reaction|side effects]] of the drug are gastrointestinal-related, and include [[steatorrhea]] (oily, loose stools with excessive [[flatus]] due to unabsorbed fats reaching the large intestine), [[fecal incontinence]] and frequent or urgent bowel movements |
The primary [[adverse drug reaction|side effects]] of the drug are gastrointestinal-related, and include [[steatorrhea]] (oily, loose stools with excessive [[flatus]] due to unabsorbed fats reaching the large intestine), [[fecal incontinence]] and frequent or urgent bowel movements.<ref>{{cite web|title=Treating Obesity|url=http://www.nhs.uk/Conditions/Obesity/Pages/Treatment.aspx|publisher=NHS|access-date=13 July 2013|archive-date=13 October 2017|archive-url=https://web.archive.org/web/20171013142422/http://www.nhs.uk/Conditions/Obesity/Pages/Treatment.aspx|url-status=live}}</ref> To minimize these effects, foods with high fat content should be avoided; the manufacturer advises consumers to follow a low-fat, reduced-calorie diet. Oily stools and flatulence can be controlled by reducing the dietary fat content to somewhere in the region of 15 grams per meal.<ref name=GSKPressRelease>{{cite press release | url = http://www.bumc.bu.edu/www/bumc/coc/pdfs/ApovianFDA.pdf | archive-url = https://wayback.archive-it.org/all/20070824165731/http://www.bumc.bu.edu/www/bumc/coc/pdfs/ApovianFDA.pdf | url-status = dead | archive-date = 24 August 2007 | title = FDA Approves alli (orlistat 60 mg capsules) Over-The-Counter | date = 7 February 2007 | access-date = 8 April 2007 | publisher = PR Newswire}}</ref> The manual for Alli makes it clear that orlistat treatment involves [[aversion therapy]], encouraging the user to associate eating fat with unpleasant treatment effects.<ref>From page 12 of the ''Alli Companion Guide'', 2007 edition: "They can be an incentive to keep from eating more fat than you really intend to."</ref> |
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Side effects are most severe when beginning therapy and may decrease in frequency with time;<ref name="Xenical FDA label" /> It has also been suggested that the decrease in side effects over time may be associated with long-term compliance with a [[low-fat diet]].<ref name=ManciniHalpern2006>{{cite journal | vauthors = Mancini MC, Halpern A | title = Pharmacological treatment of obesity | journal = Arquivos Brasileiros de Endocrinologia e Metabologia | volume = 50 | issue = 2 | pages = 377–389 | date = April 2006 | pmid = 16767304 | doi = 10.1590/S0004-27302006000200024 | title-link = doi | doi-access = free }}</ref> |
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On 26 May 2010, the [[Food and Drug Administration|U.S. Food and Drug Administration]] (FDA) approved a revised label for Xenical to include new safety information about cases of severe liver injury that have been reported rarely with the use of this medication.<ref>{{cite web|url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-completed-safety-review-xenicalalli-orlistat-and-severe-liver-injury|title=FDA Drug Safety Communication: Completed safety review of Xenical/Alli (orlistat) and severe liver injury|publisher=U.S. [[Food and Drug Administration]] (FDA)|date=28 June 2019|access-date=20 September 2022|archive-date=27 April 2022|archive-url=https://web.archive.org/web/20220427221816/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-completed-safety-review-xenicalalli-orlistat-and-severe-liver-injury|url-status=live}}</ref> |
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The side effect profile of orlistat led US [[consumer group]] Prescription Access Litigation (PAL) to award its first 2007 "Bitter Pill Award" to GlaxoSmithKline—the 'With Allies Like This, Who Needs Enemas?' Award.<ref>{{cite news | url = http://www.guardian.co.uk/health/story/0,,2176582,00.html | title = A bitter pill for slimmers? | last = Cohen | first = Deborah | accessdate = 2009-01-22 | date = September 25, 2007 | work = [[The Guardian]] | location=London}}</ref><ref>{{cite press release | url = http://www.prescriptionaccess.org/press/pressreleases?id=0041 | title = PAL Announces First Bitter Pill Award of 2007 to GlaxoSmithKline: 'With Allies Like This, Who Needs Enemas?’ Award | accessdate = 2009-01-22 | date = June 7, 2007 | publisher = Prescription Access Litigation}}</ref> |
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An analysis of over 900 orlistat users in Ontario showed that their rate of [[acute kidney injury]] was more than triple that of non-users.<ref>{{cite journal | vauthors = Weir MA, Beyea MM, Gomes T, Juurlink DN, Mamdani M, Blake PG, Wald R, Garg AX | display-authors = 6 | title = Orlistat and acute kidney injury: an analysis of 953 patients | journal = Archives of Internal Medicine | volume = 171 | issue = 7 | pages = 703–704 | date = April 2011 | pmid = 21482850 | doi = 10.1001/archinternmed.2011.103 }}</ref> |
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On May 26, 2010, the U.S. Food and Drug Administration (FDA) has approved a revised label for Xenical to include new safety information about cases of severe liver injury that have been reported rarely with the use of this medication.<ref>http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213038.htm</ref> |
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A study from 2013 looked at 94,695 participants receiving orlistat in the UK between 1999 and 2011.<ref name="pmid 23585064">{{cite journal | vauthors = Douglas IJ, Langham J, Bhaskaran K, Brauer R, Smeeth L | title = Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink | journal = BMJ | volume = 346 | pages = f1936 | date = April 2013 | pmid = 23585064 | pmc = 3624963 | doi = 10.1136/bmj.f1936 }}</ref> The study showed no evidence of an increased risk of liver injury during treatment.<ref name="pmid 23585064" /> They concluded:<ref name="pmid 23585064" /> |
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===Long-term=== |
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Despite a higher incidence of breast cancer amongst those taking orlistat in early, pooled clinical trial data—the analysis of which delayed FDA review of orlistat<ref>{{cite news | url = http://query.nytimes.com/gst/fullpage.html?res=9A0CE2DD1230F933A15752C0A96F958260&sec=&spon=&pagewanted=all | title = Obesity Drug Can Lead to Modest Weight Loss, Study Finds | last = Kolata | first = Gina | date = January 20, 1999 | accessdate = 2007-12-11 | work = [[The New York Times]]}}</ref>—a two-year study published in 1999 found similar rates between orlistat and placebo (0.54% versus 0.51%), and evidence that tumors predated treatment in 3 of the 4 participants who had them.<ref>{{cite journal |author=Davidson MH, Hauptman J, DiGirolamo M, ''et al.'' |title=Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial |journal=JAMA |volume=281 |issue=3 |pages=235–42 |year=1999 |pmid=9918478|doi=10.1001/jama.281.3.235}}</ref> There is evidence from an ''[[in vitro]]'' study to suggest that the introduction of specific varied preparations containing orlistat, namely the concurrent administration of orlistat and the [[monoclonal antibody]] [[trastuzumab]], can actually induce [[programmed cell death|cell death]] in breast cancer cells and block their growth.<ref name="Menendez et al.">{{cite journal | author = J. A. Menendez, L. Vellon and R. Lupu | title = Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene | journal = Annals of Oncology | volume = 16 | issue = 8 | pages = 1253–1267 | year = 2005 | pmid = 15870086 | doi = 10.1093/annonc/mdi239}}</ref> |
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{{blockquote|The incidence of acute liver injury was higher in the periods both immediately before and immediately after the start of orlistat treatment. This suggests that the observed increased risks of liver injury linked to the start of treatment may reflect changes in health status associated with the decision to begin treatment rather than any causal effect of the drug.}} |
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A 2006 animal study linked orlistat with [[aberrant crypt foci]] (ACF), lesions found in the [[Colon (anatomy)|colon]] which are believed to be one of the earliest precursors of [[colon cancer]].<ref name="Garcia et al.">{{cite journal | author = Garcia S, da Costa Barros L, Turatti A, Martinello F, Modiano P, Ribeiro-Silva A, de Oliveira Vespúcio M, Uyemura S | title = The anti-obesity agent Orlistat is associated to increase in colonic preneoplastic markers in rats treated with a chemical carcinogen | journal = Cancer Lett | volume = 240 | issue = 2 | pages = 221–4 | year = 2006 | pmid = 16377080 | doi = 10.1016/j.canlet.2005.09.011}}</ref><ref>{{cite journal |author=Takayama T, Katsuki S, Takahashi Y, Ohi M, Nojiri S, Sakamaki S, Kato J, Kogawa K, Miyake H, Niitsu Y |title=Aberrant crypt foci of the colon as precursors of adenoma and cancer |journal=[[New England Journal of Medicine|N Engl J Med]] |volume=339 |issue=18 |pages=1277–84 |year=1998 |pmid=9791143 |doi=10.1056/NEJM199810293391803}} [http://content.nejm.org/cgi/content/full/339/18/1277 Free full text with registration].</ref> |
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== |
=== Long-term === |
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Despite a higher incidence of [[breast cancer]] amongst those taking orlistat in early, pooled clinical trial data—the analysis of which delayed FDA review of orlistat<ref>{{cite news | url = https://www.nytimes.com/1999/01/20/us/obesity-drug-can-lead-to-modest-weight-loss-study-finds.html?pagewanted=all | title = Obesity Drug Can Lead to Modest Weight Loss, Study Finds | vauthors = Kolata G | author-link = Gina Kolata | date = 20 January 1999 | access-date = 11 December 2007 | work = [[The New York Times]] | archive-date = 13 August 2019 | archive-url = https://web.archive.org/web/20190813101733/https://www.nytimes.com/1999/01/20/us/obesity-drug-can-lead-to-modest-weight-loss-study-finds.html?pagewanted=all | url-status = live }}</ref>—a two-year study published in 1999 found similar rates between orlistat and placebo (0.54% versus 0.51%), and evidence that tumors predated treatment in 3 of the 4 participants who had them.<ref>{{cite journal | vauthors = Davidson MH, Hauptman J, DiGirolamo M, Foreyt JP, Halsted CH, Heber D, Heimburger DC, Lucas CP, Robbins DC, Chung J, Heymsfield SB | display-authors = 6 | title = Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial | journal = JAMA | volume = 281 | issue = 3 | pages = 235–242 | date = January 1999 | pmid = 9918478 | doi = 10.1001/jama.281.3.235 | title-link = doi | doi-access = free }}</ref> There is evidence from an ''[[in vitro]]'' study to suggest that the introduction of specific varied preparations containing orlistat, namely the concurrent administration of orlistat and the [[monoclonal antibody]] [[trastuzumab]], can induce [[programmed cell death|cell death]] in breast cancer cells and block their growth.<ref name="Menendez et al.">{{cite journal | vauthors = Menendez JA, Vellon L, Lupu R | title = Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast cancer cells: blockade of cell cycle progression, promotion of apoptotic cell death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene | journal = Annals of Oncology | volume = 16 | issue = 8 | pages = 1253–1267 | date = August 2005 | pmid = 15870086 | doi = 10.1093/annonc/mdi239 | title-link = doi | doi-access = }}</ref> |
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Absorption of [[Fat soluble vitamins|fat-soluble]] [[vitamin]]s and other fat-soluble nutrients is inhibited by the use of orlistat. A multivitamin tablet containing vitamins [[vitamin A|A]], [[vitamin D|D]], [[vitamin E|E]], [[vitamin K|K]], and [[beta-carotene]] should be taken once a day, at bedtime, when using orlistat.<ref name="XenicalLabel"/> |
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Fecal fat excretion promotes [[Colon (anatomy)|colon]] carcinogenesis. In 2006 the results of 30-day study were published indicating that orlistat at a dosage of 200 mg/kg chow administered to rats consuming a high-fat chow and receiving two 25 mg/kg doses of the potent carcinogen [[1,2-dimethylhydrazine]] produced significantly higher numbers of [[aberrant crypt foci]] (ACF) colon lesions than did the carcinogen plus high-fat chow without orlistat.<ref name="Garcia et al.">{{cite journal | vauthors = Garcia SB, Barros LT, Turatti A, Martinello F, Modiano P, Ribeiro-Silva A, Vespúcio MV, Uyemura SA | display-authors = 6 | title = The anti-obesity agent Orlistat is associated to increase in colonic preneoplastic markers in rats treated with a chemical carcinogen | journal = Cancer Letters | volume = 240 | issue = 2 | pages = 221–224 | date = August 2006 | pmid = 16377080 | doi = 10.1016/j.canlet.2005.09.011 }}</ref> ACF lesions are believed to be one of the earliest precursors of [[colon cancer]].<ref>{{cite journal | vauthors = Takayama T, Katsuki S, Takahashi Y, Ohi M, Nojiri S, Sakamaki S, Kato J, Kogawa K, Miyake H, Niitsu Y | display-authors = 6 | title = Aberrant crypt foci of the colon as precursors of adenoma and cancer | journal = The New England Journal of Medicine | volume = 339 | issue = 18 | pages = 1277–1284 | date = October 1998 | pmid = 9791143 | doi = 10.1056/NEJM199810293391803 | doi-access = free }}</ref> |
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On June 4, 2009, the U.S. Food and Drug Administration released its quarterly list of drugs that are under investigation for potential safety issues or new safety information. Orlistat was included in the list as having a "Potential Signal of Serious Risk" of [[hepatotoxicity|liver toxicity]], meaning that a potential risk of liver toxicity was identified based on reports to the FDA [[Adverse Event Reporting System]] between October and December 2008.<ref name=AERS>{{cite web |url=http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm161063.htm |title=Potential Signals of Serious Risks/New Safety Information Identified from the Adverse Event Reporting System (AERS) between October - December 2008 |publisher=U.S. Food and Drug Administration |date=June 4, 2009 |accessdate=2009-06-08}}</ref> Isolated cases of orlistat-associated liver problems have been reported before.<ref name=Filippatos>{{cite journal |author=Filippatos TD, Derdemezis CS, Gazi IF, Nakou ES, Mikhailidis DP, Elisaf MS |title=Orlistat-associated adverse effects and drug interactions: a critical review |journal=Drug Saf |volume=31 |issue=1 |pages=53–65 |year=2008 |pmid=18095746 |doi=10.2165/00002018-200831010-00005}}</ref> On August 24, the FDA reported that it would investigate 30 cases of liver damage reported between 1999 and October 2008 in patients taking orlistat, including six cases of [[liver failure]].<ref>{{cite news |url=http://abcnews.go.com/Health/Healthday/story?id=8410115 |title=U.S. probes Roche, Glaxo diet drug over liver injury |date=August 24, 2009 |publisher=[[ABC News]] |accessdate=2009-08-24}}</ref> |
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=== Precautions === |
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Absorption of [[Fat soluble vitamins|fat-soluble]] [[vitamin]]s and other fat-soluble nutrients is inhibited by the use of orlistat.<ref name="Xenical FDA label" /> |
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Orlistat may reduce plasma levels of [[ciclosporin]] (also known as "cyclosporin" or "cyclosporine", trade names Sandimmune, Gengraf, Neoral, etc.)<!--"ciclosporin" is the International Nonproprietary Name, not a typo; please do not alter the spelling without discussing-->, an [[immunosuppressive drug]] frequently used to prevent [[transplant rejection]]; the two drugs should therefore not be administered concomitantly.<ref name="XenicalLabel"/> Orlistat can also impair absorption of the [[antiarrhythmic agent|antiarrhythmic]] [[amiodarone]].<ref>{{cite journal |author=Zhi J, Moore R, Kanitra L, Mulligan TE |title=Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin) in healthy volunteers |journal=J Clin Pharmacol |volume=43 |issue=4 |pages=428–35 |year=2003 |pmid=12723464 |doi=10.1177/0091270003252236}}</ref> |
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=== Interactions === |
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==Contraindications== |
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Orlistat may reduce plasma levels of [[ciclosporin]] (also known as "cyclosporin" or "cyclosporine", trade names Sandimmune, Gengraf, Neoral, etc.)<!-- "ciclosporin" is the International Nonproprietary Name, not a typo; please do not alter the spelling without discussing -->, an [[immunosuppressive drug]] frequently used to prevent [[transplant rejection]]; the two drugs should therefore not be administered concomitantly.<ref name="Xenical FDA label" /> Orlistat can also impair absorption of the [[antiarrhythmic agent|antiarrhythmic]] [[amiodarone]].<ref>{{cite journal | vauthors = Zhi J, Moore R, Kanitra L, Mulligan TE | title = Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin) in healthy volunteers | journal = Journal of Clinical Pharmacology | volume = 43 | issue = 4 | pages = 428–435 | date = April 2003 | pmid = 12723464 | doi = 10.1177/0091270003252236 | s2cid = 24389189 }}</ref> The [[Medicines and Healthcare products Regulatory Agency]] (MHRA) has suggested the possibility that orlistat could reduce the absorption of [[antiretroviral]] [[HIV]] medications.<ref>{{cite web | title = Orlistat: theoretical interaction with antiretroviral HIV medicines | publisher = [[Medicines and Healthcare products Regulatory Agency]] (MHRA) | date = 13 March 2014 | url = http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON392868 | access-date = 16 November 2014 | archive-date = 29 November 2014 | archive-url = https://web.archive.org/web/20141129023225/http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON392868 | url-status = live }}</ref> |
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Orlistat is [[Contraindication|contraindicated]] in:<ref name="XenicalLabel"/> |
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* [[Malabsorption]] |
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* Hypersensitivity to orlistat |
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* Reduced [[gallbladder]] function (e.g. after [[cholecystectomy]]) |
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* [[Pregnancy]] and [[breastfeeding]] |
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* Use caution with: obstructed [[bile duct]], impaired liver function, and [[pancreatic disease]] |
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<!--* Certain [[kidney]] problems--> |
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== Mechanism of action == |
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==Availability== |
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[[File:2PX6 orlistat.png|thumb|270px|[[X-ray crystallography#Biological macromolecular crystallography|Crystallographic structure]] of human [[fatty acid synthase]] thioesterase (rainbow color, [[N-terminus]] = blue, [[C-terminus]] = red) inhibited by orlistat ([[space-filling model]]; carbon = grey, oxygen = red, nitrogen = blue)<ref name="pmid17618296">{{PDB|2PX6}}; {{cite journal | vauthors = Pemble CW, Johnson LC, Kridel SJ, Lowther WT | title = Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat | journal = Nature Structural & Molecular Biology | volume = 14 | issue = 8 | pages = 704–709 | date = August 2007 | pmid = 17618296 | doi = 10.1038/nsmb1265 | s2cid = 2105534 }}</ref>]] |
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[[File:Xenical.JPG|thumb|Packaging of orlistat (Xenical) 120 mg capsules, as sold in Canada.]] |
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Orlistat has historically been available by prescription only, and this situation continues in [[Canada]]. In Australia, the [[EU|European Union]],<ref name=BBC/> and the United States, certain formulations of orlistat have been approved for sale [[over-the-counter drug|without a prescription]]. |
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Orlistat works by inhibiting gastric and pancreatic [[lipases]], the [[enzyme]]s that break down [[triglycerides]] in the [[intestine]].<ref>{{cite journal | vauthors = Heck AM, Yanovski JA, Calis KA | title = Orlistat, a new lipase inhibitor for the management of obesity | journal = Pharmacotherapy | volume = 20 | issue = 3 | pages = 270–279 | date = March 2000 | pmid = 10730683 | pmc = 6145169 | doi = 10.1592/phco.20.4.270.34882 | name-list-style = vanc }}</ref><ref>{{Cite web| vauthors = Higham G |title= Orlistat & Xenical: Do Weight Loss Pills Work? {{!}} e-Surgery|url=https://e-surgery.com/orlistat-xenical-do-weight-loss-pills-work/|access-date=2020-06-09|website=e-surgery|date=5 June 2020|name-list-style=vanc|archive-date=16 January 2021|archive-url=https://web.archive.org/web/20210116014955/https://e-surgery.com/orlistat-xenical-do-weight-loss-pills-work/|url-status=live}}</ref> When lipase activity is blocked, triglycerides from the diet are not [[hydrolysis|hydrolyzed]] into absorbable free [[fatty acid]]s, and instead are excreted unchanged. Only trace amounts of orlistat are absorbed systemically; the primary effect is local lipase inhibition within the [[gastrointestinal tract|GI tract]] after an oral dose. The primary route of elimination is through the [[feces]]. |
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In 2009, [[Hoffmann–La Roche|Roche]] began recruiting in Russia for a clinical trial of Xenical in obese teenagers between the ages of 12 and 14.<ref>{{ClinicalTrialsGov|NCT00940628}}</ref> |
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Orlistat was also found to [[Discovery and development of gastrointestinal lipase inhibitors#Mechanism of action|inhibit the thioesterase domain of fatty acid synthase (FAS)]], an enzyme involved in the proliferation of cancer cells but not normal cells. However, potential side effects of orlistat, such as inhibition of other cellular off-targets or poor bioavailability, might hamper its application as an effective antitumor agent. One profiling study undertook a chemical proteomics approach to look for new cellular targets of orlistat, including its off-targets.<ref>{{cite journal | vauthors = Yang PY, Liu K, Ngai MH, Lear MJ, Wenk MR, Yao SQ | title = Activity-based proteome profiling of potential cellular targets of Orlistat--an FDA-approved drug with anti-tumor activities | journal = Journal of the American Chemical Society | volume = 132 | issue = 2 | pages = 656–666 | date = January 2010 | pmid = 20028024 | doi = 10.1021/ja907716f | url = https://www.researchgate.net/publication/40758526 | access-date = 19 April 2019 | url-status = live | name-list-style = vanc | archive-url = https://web.archive.org/web/20211025174008/https://www.researchgate.net/publication/40758526_Activity-Based_Proteome_Profiling_of_Potential_Cellular_Targets_of_Orlistat_-_An_FDA-Approved_Drug_with_Anti-Tumor_Activities | archive-date = 25 October 2021 }}</ref> Orlistat also shows potential activity against the ''[[Trypanosoma brucei]]'' parasite.<ref>{{cite journal | vauthors = Yang PY, Wang M, Liu K, Ngai MH, Sheriff O, Lear MJ, Sze SK, He CY, Yao SQ | display-authors = 6 | title = Parasite-based screening and proteome profiling reveal orlistat, an FDA-approved drug, as a potential anti Trypanosoma brucei agent | journal = Chemistry: A European Journal | volume = 18 | issue = 27 | pages = 8403–8413 | date = July 2012 | pmid = 22674877 | doi = 10.1002/chem.201200482 | url = https://pubmed.ncbi.nlm.nih.gov/22674877/?from_single_result=orlistat+mycobacteria+Trypanosoma+brucei | access-date = 9 June 2020 | url-status = live | name-list-style = vanc | archive-url = https://web.archive.org/web/20200609230034/https://pubmed.ncbi.nlm.nih.gov/22674877/?from_single_result=orlistat+mycobacteria+Trypanosoma+brucei | archive-date = 9 June 2020 }}</ref> |
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===Australia and New Zealand=== |
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In Australia and New Zealand, orlistat is {{As of|2009|alt=currently}} available [[over-the-counter drug|over-the-counter]] in 120 mg size (84 capsules to the pack). Initially available only with a prescription, it was reclassified as a "[[Standard for the Uniform Scheduling of Drugs and Poisons#Schedule 3 Pharmacist Only Medicine|Pharmacist Only Medicine]]" in October 2003. In late 2006, the [[Australian Consumers' Association]] complained that Roche was inappropriately advertising the drug to teenagers, and Roche was forced to withdraw its ads.<ref name=CHOICE>{{cite web | url = http://www.choice.com.au/viewArticle.aspx?id=104825&catId=100386&tid=100008&p=2&title=Drug+advertising | title = Drug advertising: Xenical | accessdate = 2007-02-16 | month = February | year = 2007 | publisher = CHOICE}}</ref> The Association filed further complaints<ref name=CHOICE/> with the [[Therapeutic Goods Administration]]—TGA, Australia's regulatory authority for healthcare products—and the TGA's Scheduling Committee agreed to convene on February 20, 2007, to discuss possible revoking of orlistat's over-the-counter status.<ref>{{cite news | url = http://www.news.com.au/dailytelegraph/story/0,22049,21170905-5006009,00.html | title = Weight drugs danger revealed | accessdate = 2007-02-16 | date = February 5, 2007 | last = Bissett | first = Kelvin | publisher = [[The Daily Telegraph (Australia)|The Daily Telegraph]]}}</ref> The Committee ultimately decided to keep orlistat as a [[Standard for the Uniform Scheduling of Drugs and Poisons|Schedule 3 drug]], but withdrew its authorization of direct-to-consumer Xenical advertising, stating this "increased pressure on pharmacists to provide orlistat to consumers...this in turn had the potential to result in inappropriate patterns of use".<ref>{{cite press release | url = http://www.tga.gov.au/media/2007/070222-orlistat.htm | title = Scheduling of orlistat | date = February 22, 2007 | accessdate = 2007-03-03 | publisher = [[Australia]]n [[Therapeutic Goods Administration]]}}</ref> Xenical has recently began being advertised direct-to-customers again. |
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Orlistat prevents approximately 30% of dietary fat from being absorbed.<ref name="PDR">{{cite book |title= 2006 Physicians' Desk Reference (PDR) |url= https://archive.org/details/physiciandeskref00mont |url-access= registration |year= 2006 |publisher= Thomson PDR |isbn= 978-1-56363-527-4}}</ref> |
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===United States=== |
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On January 23, 2006, a U.S. [[Food and Drug Administration]] advisory panel voted 11 to 3 to recommend the approval of an OTC formulation of orlistat, to be marketed under the name '''alli''' ({{pronEng|ˈælaɪ}}, like the English word "ally") by [[GlaxoSmithKline]].<ref name="WP">{{cite news | title = Panel Supports Offering Diet Pill Orlistat Over the Counter | pages = A02 | work = [[The Washington Post]] | date = January 24, 2006 | url = http://www.washingtonpost.com/wp-dyn/content/article/2006/01/23/AR2006012301507.html | accessdate = 2006-08-10}}</ref> Approval was granted on February 7, 2007,<ref>{{cite press release | url = http://www.fda.gov/bbs/topics/NEWS/2007/NEW01557.html | title = FDA Approves Orlistat for Over-the-Counter Use | accessdate = 2007-02-07 | date = February 7, 2007 | publisher = U.S. [[Food and Drug Administration]]}}</ref> and alli became the first weight loss drug officially sanctioned by the U.S. government for over-the-counter use.<ref name="NYT">{{cite news | url = http://www.nytimes.com/2007/02/07/health/07cnd-diet.html | title = Weight-Loss Drug to Be Sold Over the Counter | accessdate = 2007-02-10 | last = Saul | first = Stephanie | date = February 7, 2007 | work = The New York Times}}</ref> |
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Consumer advocacy organization [[Public Citizen]], through its Health Research Group, opposed over-the-counter approval for orlistat, calling it "the height of recklessness" and "a dangerous mistake" due to questionable benefits and possible adverse effects.<ref name="WP2">{{cite news | url = http://www.usatoday.com/news/health/2007-02-09-diet-pill_x.htm | title = FDA OKs First Nonprescription Diet Pill | accessdate = 2009-06-09 | last = Schmid | first = Randolph E | date = February 9, 2007 | work = [[USA Today]]}}</ref> Public Citizen had already called for a ban of orlistat in April 2006.<ref>Press Release. [http://www.citizen.org/pressroom/release.cfm?ID=2174 Public Citizen Petitions FDA to Ban Xenical (orlistat)]. Public Citizen.</ref> |
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== Legal status == |
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Alli became available in the U.S. in June 2007. It is sold as 60 mg capsules—half the dosage of prescription orlistat.<ref name="WP2"/><ref name="NYT"/> |
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Orlistat is available both with and [[over-the-counter drug|without a prescription]].<ref name=BBC /><ref name="Xenical FDA label" /><ref name="Alli FDA label" /><ref>{{cite web | title=Orlistat | website=European Medicines Agency | url=https://www.ema.europa.eu/en/medicines/human/referrals/orlistat | access-date=19 September 2022 | archive-date=5 December 2020 | archive-url=https://web.archive.org/web/20201205011518/https://www.ema.europa.eu/en/medicines/human/referrals/orlistat | url-status=live }}</ref> |
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=== Australia and New Zealand === |
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===European Union=== |
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In Australia and New Zealand, orlistat is available as a "[[Standard for the Uniform Scheduling of Drugs and Poisons#Schedule 3 Pharmacist Only Medicine|Pharmacist Only Medicine]]".<ref name=TGAauth>{{cite web|title=Orlistat 120mg capsule blister pack|url=https://www.ebs.tga.gov.au/servlet/xmlmillr6?dbid=ebs/PublicHTML/pdfStore.nsf&docid=61598&agid=(PrintDetailsPublic)&actionid=1|publisher=TGA|access-date=18 April 2018|date=11 April 2000}}</ref> In 2007, the Committee decided to keep orlistat as a [[Standard for the Uniform Scheduling of Drugs and Poisons|Schedule 3 drug]], but withdrew its authorization of direct-to-consumer Xenical advertising, stating this "increased pressure on pharmacists to provide orlistat to consumers...this in turn had the potential to result in inappropriate patterns of use".<ref name=TGApr>{{cite press release | url = http://www.tga.gov.au/media/2007/070222-orlistat.htm | title = Scheduling of orlistat | date = 22 February 2007| publisher = Australian Therapeutic Goods Administration|archive-url=https://web.archive.org/web/20071229065506/http://www.tga.gov.au/media/2007/070222-orlistat.htm|archive-date=29 December 2007}}</ref> |
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=== United States === |
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On January 21, 2009, the [[European Medicines Agency]] granted approval for the sale of orlistat without a prescription.<ref name=BBC>{{cite news | url = http://news.bbc.co.uk/1/hi/health/7843061.stm | title = Chemists to provide obesity pill | accessdate = 2009-01-22 | date = January 21, 2009 | publisher = [[BBC News]]}}</ref><ref>{{cite press release | url = http://www.gsk.com/media/pressreleases/2009/2009_pressrelease_10011.htm | title = GlaxoSmithKline receives European Commission approval to market alli (orlistat 60mg) | accessdate = 2009-01-22 | date = January 21, 2009 | publisher = GlaxoSmithKline}}</ref> |
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Orlistat was initially approved by the [[Food and Drug Administration|U.S. Food and Drug Administration]] in April 1999 as a prescription-only medication.<ref name="Stolberg 1999">{{cite web |last=Stolberg |first=Sheryl |title=F.D.A. Approves Fat-Blocking Anti-Obesity Drug |website=The New York Times |date=27 April 1999 |url=https://www.nytimes.com/1999/04/27/us/fda-approves-fat-blocking-anti-obesity-drug.html |access-date=20 April 2023}}</ref> On 23 January 2006, an FDA advisory panel voted 11 to 3 to recommend the approval of an OTC formulation of orlistat, to be sold under the brand name Alli by [[GlaxoSmithKline]].<ref name="WP">{{cite news | title = Panel Supports Offering Diet Pill Orlistat Over the Counter | pages = A02 | newspaper = [[The Washington Post]] | date = 24 January 2006 | url = https://www.washingtonpost.com/wp-dyn/content/article/2006/01/23/AR2006012301507.html | access-date = 10 August 2006 | archive-date = 25 October 2021 | archive-url = https://web.archive.org/web/20211025174027/https://www.washingtonpost.com/wp-dyn/content/article/2006/01/23/AR2006012301507.html | url-status = live }}</ref> Approval was granted on 7 February 2007,<ref>{{cite press release | url = https://www.fda.gov/bbs/topics/NEWS/2007/NEW01557.html | title = FDA Approves Orlistat for Over-the-Counter Use | access-date = 7 February 2007 | date = 7 February 2007 | publisher = [[Food and Drug Administration|U.S. Food and Drug Administration]] (FDA) | archive-date = 13 May 2009 | archive-url = https://web.archive.org/web/20090513070820/http://www.fda.gov/bbs/topics/NEWS/2007/NEW01557.html | url-status = dead }}</ref> and Alli became the first weight loss drug officially sanctioned by the U.S. government for over-the-counter use.<ref name="NYT">{{cite news | url = https://www.nytimes.com/2007/02/07/health/07cnd-diet.html | title = Weight-Loss Drug to Be Sold Over the Counter | access-date = 10 February 2007 | vauthors = Saul S | date = 7 February 2007 | work = The New York Times | name-list-style = vanc | archive-date = 25 October 2021 | archive-url = https://web.archive.org/web/20211025173812/https://www.nytimes.com/2007/02/07/health/07cnd-diet.html | url-status = live }}</ref> |
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Consumer advocacy organization [[Public Citizen]] opposed over-the-counter approval for orlistat.<ref name="WP2">{{cite news | url = https://www.usatoday.com/news/health/2007-02-09-diet-pill_x.htm | title = FDA OKs First Nonprescription Diet Pill | access-date = 9 June 2009 | vauthors = Schmid RE | date = 9 February 2007 | work = [[USA Today]] | name-list-style = vanc | archive-date = 25 October 2021 | archive-url = https://web.archive.org/web/20211025173953/https://usatoday30.usatoday.com/news/health/2007-02-09-diet-pill_x.htm | url-status = live }}</ref> |
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Alli became available in the U.S. in June 2007. It is sold as 60 mg capsules—half the dosage of prescription orlistat.<ref name="WP2" /><ref name="NYT" /> |
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===Generic formulations=== |
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{{As of|2009|9}}, no [[generic drug|generic]] formulations of orlistat are legally available in the United States. U.S. patent protection for Xenical, originally to end on June 18, 2004, was extended by five years (until 2009) by the U.S. [[United States Patent and Trademark Office|Patent and Trademark Office]]. The extension was granted on July 20, 2002,<ref>{{cite web | url = http://www.uspto.gov/web/offices/pac/dapp/opla/term/certs/4598089.pdf | title = Certificate Extending Patent Term Under 35 U.S.C. § 156 | last = Rogan | first = James E. | format = [[PDF]], 32 KiB | authorlink = Jim Rogan | date = July 30, 2002 | accessdate = 2007-04-08 | publisher = [[United States Patent and Trademark Office]]}}</ref> and expired on June 18, 2009.<ref>"Drug Patent Expirations in June 2009". DrugPatentWatch.com, in {{cite web |url=http://www.biotechblog.com/2009/06/01/drug-patent-expirations-in-june-2009 |title=Drug Patent Expirations in June 2009 |date=June 1, 2009 |publisher=Biotech Blog |accessdate=2009-06-20}}</ref> |
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=== European Union and Switzerland === |
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Generic orlistat is available in India, under the brands Olistat, Vyfat, Obelit, and Reeshape.<ref>{{cite news |last=Devarajan |first=Uma |title=Fatty issues |work=[[The Deccan Chronicle]] |date=March 1, 2009 |url=http://www.deccanchronicle.com/sunday-debate/fatty-issues-694 |accessdate=2009-11-26}}</ref> |
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On 21 January 2009, the [[European Medicines Agency]] granted approval for the sale of orlistat without a prescription.<ref name=BBC>{{cite news | url = http://news.bbc.co.uk/2/hi/health/7843061.stm | title = Chemists to provide obesity pill | access-date = 22 January 2009 | date = 21 January 2009 | publisher = [[BBC News Online]] | archive-date = 23 January 2009 | archive-url = https://web.archive.org/web/20090123123722/http://news.bbc.co.uk/2/hi/health/7843061.stm | url-status = live }}</ref><ref>{{cite press release | url = http://www.gsk.com/media/pressreleases/2009/2009_pressrelease_10011.htm | title = GlaxoSmithKline receives European Commission approval to market alli (orlistat 60mg) | access-date = 22 January 2009 | date = 21 January 2009 | publisher = GlaxoSmithKline | url-status = dead | archive-url = https://web.archive.org/web/20090127012016/http://www.gsk.com/media/pressreleases/2009/2009_pressrelease_10011.htm | archive-date = 27 January 2009}}</ref> |
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==Criticism== |
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{{Expand section|date=May 2010}} |
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Glaxo was criticized for financing a documentary about eating.<ref>{{cite news|url=http://www.nytimes.com/2010/01/07/business/media/07documentary.html|title=Diet Drug Maker Glaxo to Pay for a Film on Eating|first=BROOKS BARNES|date=6 January 2010|work=The New York Times|accessdate=12 January 2010}}</ref> |
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At least since September 2017, tablets with 60 mg orlistat can be freely sold in Swiss drugstores. Formulations with 120 mg per tablet require a prescription, but can be sold without one in pharmacies under an exemption rule, which is based on a list of easily diagnosable diseases.<ref>http://www.compendium.ch {{Webarchive|url=https://web.archive.org/web/20211010033345/https://www.compendium.ch/ |date=10 October 2021 }}, directory of drugs approved in Switzerland</ref> |
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==Counterfeit products== |
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In January 2010, the United States [[Food and Drug Administration]] issued an alert stating that some counterfeit versions of Alli sold over the Internet contain no orlistat, and instead contain the weight-loss drug [[sibutramine]]. The concentration of sibutramine in these counterfeit products is at least twice the amount recommended for weight loss. <ref>{{cite news |publisher= CNN.com |url= http://www.cnn.com/2010/HEALTH/01/23/fake.diet.drug/index.html |title= Fake Alli diet pills can pose health risks |accessdate= 2010-01-24 | date=2010-01-23}}</ref> |
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=== Generic formulations === |
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==References== |
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U.S. patent protection for Xenical, originally to end on 18 June 2004, was extended by five years (until 2009) by the U.S. [[United States Patent and Trademark Office|Patent and Trademark Office]]. The extension was granted on 20 July 2002,<ref>{{cite web | url = http://www.uspto.gov/web/offices/pac/dapp/opla/term/certs/4598089.pdf | title = Certificate Extending Patent Term Under 35 U.S.C. § 156 | vauthors = Rogan JE | author-link = Jim Rogan | date = 30 July 2002 | access-date = 8 April 2007 | publisher = [[United States Patent and Trademark Office]] | name-list-style = vanc | archive-date = 29 September 2006 | archive-url = https://web.archive.org/web/20060929133007/http://www.uspto.gov/web/offices/pac/dapp/opla/term/certs/4598089.pdf | url-status = live }}</ref> and expired on 18 June 2009.<ref>"Drug Patent Expirations in June 2009". DrugPatentWatch.com, in {{cite web |url=http://www.biotechblog.com/2009/06/01/drug-patent-expirations-in-june-2009 |title=Drug Patent Expirations in June 2009 |date=1 June 2009 |publisher=Biotech Blog |access-date=20 June 2009 |archive-url=https://web.archive.org/web/20090609085725/http://www.biotechblog.com/2009/06/01/drug-patent-expirations-in-june-2009/ |archive-date=9 June 2009 |url-status=dead }}</ref> |
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{{Reflist|colwidth=30em}} |
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Generic orlistat is available in Iran under the brand Venustat manufactured by Aburaihan Pharmaceutical co., in India, under the brands Orlean (Eris), Vyfat, Olistat, Obelit, Orlica and Reeshape.<ref>{{cite news | vauthors = Devarajan U |title=Fatty issues |work=[[The Deccan Chronicle]] |date=1 March 2009 |url=http://www.deccanchronicle.com/sunday-debate/fatty-issues-694 |access-date=26 November 2009 |name-list-style=vanc |archive-date=10 March 2009 |archive-url=https://web.archive.org/web/20090310042334/http://deccanchronicle.com/sunday-debate/fatty-issues-694 |url-status=dead }}</ref> In Russia, orlistat is available under the brand names Xenical ([[Hoffmann–La Roche]]), Orsoten/Orsoten Slim ([[Krka (company)|KRKA d. d.]]) and Xenalten (OBL-Pharm). In Austria, orlistat is available under the brand name Slimox. In Malaysia, orlistat is available under the brand name Cuvarlix and is marketed by Pharmaniaga. In the Philippines orlistat is available under the brand name RedoXfat Plus manufactured by ATC Healthcare |
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==Further reading== |
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<!--regarding Orlistat's chemistry--> |
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*{{Cite journal|doi=10.1021/jm00029a013|title=Synthesis of high specific activity tritium-labeled [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties|pmid=8308867|year=1994|last1=Boehm|first1=Marcus F.|last2=McClurg|first2=Michael R.|last3=Pathirana|first3=Charles|last4=Mangelsdorf|first4=David|last5=White|first5=Steven K.|last6=Hebert|first6=Jonathan|last7=Winn|first7=David|last8=Goldman|first8=Mark E.|last9=Heyman|first9=Richard A.|journal=Journal of Medicinal Chemistry|volume=37|issue=3|pages=408}} |
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*{{Cite journal|doi=10.1021/jo00079a022|title=Total synthesis of (-)-tetrahydrolipstatin|year=1993|last1=Hanessian|first1=Stephen|last2=Tehim|first2=Ashok|last3=Chen|first3=Ping|journal=The Journal of Organic Chemistry|volume=58|pages=7768}} |
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== |
==Society and culture== |
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{{Portal|Pharmacy and Pharmacology}} |
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===Cost=== |
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* [http://www.myalli.com/ Official US alli site from GlaxoSmithKline] |
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At times, such as in spring 2012, orlistat has come into short supply, with consequent price increases because of nonavailability of one of the drug's components.<ref>{{cite news |
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* [http://www.alli.co.uk/ Official UK alli site from GlaxoSmithKline] |
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| date = 20 April 2012 |
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* [http://www.xenical.com/ Official Xenical site from Roche] |
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| title = Glaxo Sells Bulk of Over-the-Counter Drugs |
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* [http://web.archive.org/web/20080126112525/http://www.fda.gov/cder/consumerinfo/druginfo/xenical.htm FDA Consumer Info] |
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| author = Jeanne Whalen |
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| work = [[The Wall Street Journal]] |
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| url = https://www.wsj.com/articles/SB10001424052702303513404577355810163684518 |
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| quote = Glaxo said the issue wasn't a lack of interested buyers, but manufacturing problems that have led to shortages of the diet pill and forced the company to delay the product's sale. |
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| access-date = 8 August 2017 |
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| archive-date = 27 August 2016 |
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| archive-url = https://web.archive.org/web/20160827110355/http://www.wsj.com/articles/SB10001424052702303513404577355810163684518 |
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| url-status = live |
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}}</ref> |
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=== Counterfeit products === |
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In January 2010, the [[Food and Drug Administration|U.S. Food and Drug Administration]] issued an alert stating that some counterfeit versions of Alli sold over the Internet contain no orlistat, and instead contain the weight-loss drug [[sibutramine]]. The concentration of sibutramine in these counterfeit products is at least twice the amount recommended for weight loss.<ref>{{cite news |publisher= CNN |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= 24 January 2010 |date= 23 January 2010 |archive-date= 25 January 2010 |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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== References == |
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{{Reflist}} |
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== Further reading == |
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<!-- regarding orlistat's chemistry --> |
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{{refbegin}} |
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* {{cite journal | vauthors = Boehm MF, McClurg MR, Pathirana C, Mangelsdorf D, White SK, Hebert J, Winn D, Goldman ME, Heyman RA | display-authors = 6 | title = Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties | journal = Journal of Medicinal Chemistry | volume = 37 | issue = 3 | pages = 408–414 | date = February 1994 | pmid = 8308867 | doi = 10.1021/jm00029a013 }} |
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* {{cite journal|doi=10.1021/jo00079a022|title=Total synthesis of (−)-tetrahydrolipstatin|year=1993| vauthors = Hanessian S, Tehim A, Chen P |journal=The Journal of Organic Chemistry|volume=58|page=7768|issue=27 }} |
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* {{cite journal | vauthors = Yang PY, Liu K, Ngai MH, Lear MJ, Wenk MR, Yao SQ | title = Activity-based proteome profiling of potential cellular targets of Orlistat--an FDA-approved drug with anti-tumor activities | journal = Journal of the American Chemical Society | volume = 132 | issue = 2 | pages = 656–666 | date = January 2010 | pmid = 20028024 | doi = 10.1021/ja907716f | name-list-style = vanc }} |
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* {{cite journal | vauthors = Yang PY, Wang M, Liu K, Ngai MH, Sheriff O, Lear MJ, Sze SK, He CY, Yao SQ | display-authors = 6 | title = Parasite-based screening and proteome profiling reveal orlistat, an FDA-approved drug, as a potential anti Trypanosoma brucei agent | journal = Chemistry: A European Journal | volume = 18 | issue = 27 | pages = 8403–8413 | date = July 2012 | pmid = 22674877 | doi = 10.1002/chem.201200482 | name-list-style = vanc }} |
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{{refend}} |
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== External links == |
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* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/orlistat | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Orlistat }} |
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