Metoclopramide#Brand names

Image:Metoclopramide-5mg.jpg

Metoclopramide is commonly used to treat nausea and vomiting associated with conditions such as uremia, radiation sickness, cancer and the effects of chemotherapy, labor, infection, and emetogenic drugs.{{cite web| publisher = Valeant Pharmaceuticals| title = Maxolon (Australian Approved Product Information)| url =http://www.mydr.com.au/medicines/cmis/maxolon-tablets| year = 2000| url-status = dead| archive-url =https://web.archive.org/web/20111107203809/http://www.mydr.com.au/medicines/cmis/maxolon-tablets| archive-date = 7 November 2011}}

{{cite book| editor = Rossi S.| title = Australian Medicines Handbook| year = 2006| location = Adelaide| publisher = Australian Medicines Handbook| isbn = 978-0-9757919-2-9}}{{cite web|url=http://xpil.medicines.org.uk/ViewPil.aspx?DocID=8068|title=Metoclopramide Hydrochloride 5mg/5ml Oral Solution - - (eMC)|website=xpil.medicines.org.uk|access-date=22 July 2013|archive-date=3 March 2016|archive-url=https://web.archive.org/web/20160303222308/http://xpil.medicines.org.uk/ViewPil.aspx?DocID=8068|url-status=dead}} As a perioperative anti-emetic, the effective dose is usually 25 to 50 mg (compared to the usual 10 mg dose).

It is also used in pregnancy as a second choice for treatment of hyperemesis gravidarum (severe nausea and vomiting of pregnancy).

It is also used preventatively by some EMS providers when transporting people who are conscious and spinally immobilized."Ambulance Victoria Clinical Guideline A0701"{{cite web |url=http://www.ambulance.vic.gov.au/media/docs/Adult%20CPG%20wm-a01f0e1e-4fc0-405c-bc83-3136adf4a723-0.pdf |title=Oxygen Therapy | work = Ambulance Victoria | date = 2013 |access-date=5 December 2014 |url-status=dead |archive-url= https://web.archive.org/web/20150312004916/http://www.ambulance.vic.gov.au/media/docs/Adult%20CPG%20wm-a01f0e1e-4fc0-405c-bc83-3136adf4a723-0.pdf |archive-date=12 March 2015 }}

In migraine headaches, metoclopramide may be used in combination with paracetamol (acetaminophen) or in combination with aspirin.{{cite journal | vauthors = Derry S, Moore RA | title = Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD008040 | date = April 2013 | volume = 2013 | pmid = 23633349 | pmc = 4161111 | doi = 10.1002/14651858.CD008040.pub3 }}

Evidence also supports its use for gastroparesis, a condition that causes the stomach to empty poorly, and as of 2010 it was the only drug approved by the FDA for that condition.

It is also used in gastroesophageal reflux disease.{{cite web | title=Reglan- metoclopramide hydrochloride tablet | website=DailyMed | date=19 June 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de55c133-eb08-4a35-91a2-5dc093027397 | access-date=22 November 2020 | archive-date=30 November 2020 | archive-url=https://web.archive.org/web/20201130142342/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de55c133-eb08-4a35-91a2-5dc093027397 | url-status=live }}

While metoclopramide is used to increase breast milk production, evidence for its effectiveness for this indication is poor.{{cite journal | vauthors = Bazzano AN, Hofer R, Thibeau S, Gillispie V, Jacobs M, Theall KP | title = A Review of Herbal and Pharmaceutical Galactagogues for Breast-Feeding | journal = The Ochsner Journal | volume = 16 | issue = 4 | pages = 511–524 | date = 2016 | pmid = 27999511 | pmc = 5158159 }} Its safety for this use is also unclear.{{cite journal | vauthors = Forinash AB, Yancey AM, Barnes KN, Myles TD | title = The use of galactagogues in the breastfeeding mother | journal = The Annals of Pharmacotherapy | volume = 46 | issue = 10 | pages = 1392–1404 | date = October 2012 | pmid = 23012383 | doi = 10.1345/aph.1R167 | s2cid = 207264697 }}

Intravenous metoclopramide is used in small-bowel follow-through, small-bowel enema, and radionuclide gastric-emptying studies to reduce the time taken for the barium to go through the intestines, thus reducing the total time needed for the procedures. Metoclopramide also prevents vomiting after oral ingestion of barium.{{cite book | vauthors = Watson N, Jones H |title=Chapman and Nakielny's Guide to Radiological Procedures |date=2018 |publisher=Elsevier |isbn=978-0-7020-7166-9 |pages=48, 55, 87}}

Metoclopramide is contraindicated in pheochromocytoma. It should be used with caution in Parkinson's disease since, as a dopamine antagonist, it may worsen symptoms. Long-term use should be avoided in people with clinical depression, as it may worsen one's mental state. It is contraindicated for people with a suspected bowel obstruction, in epilepsy, if a stomach operation has been performed in the previous three or four days, perforation or blockage of the stomach, and in newborn babies.

The European Medicines Agency reviewed the drug's safety in 2011, which determined that it should not be prescribed in high doses, for periods of more than five days, or given to children below 1 year of age. They suggested its use in older children should be restricted to treating post-chemotherapy or post-surgery nausea and vomiting, and even then only for patients where other treatments have failed. For adults, they recommended its use be restricted to treating migraines and post-chemotherapy or post-surgery patients.{{cite web | title = Metoclopramide-containing medicines | work = European Medicines Agency | date = 17 September 2018 | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Metoclopramide-containing_medicines/human_referral_000349.jsp&mid=WC0b01ac05805c516f | access-date = 25 August 2016 | archive-date = 20 June 2018 | archive-url = https://web.archive.org/web/20180620183118/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Freferrals%2FMetoclopramide-containing_medicines%2Fhuman_referral_000349.jsp&mid=WC0b01ac05805c516f | url-status = dead }}{{cite web | title = Metoclopramide only containing medicinal products | url = http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Metoclopramide_31/WC500160356.pdf | work = EMA/753989/2013 Assessment report | date = 20 December 2013 | publisher = European Medicines Agency | access-date = 25 August 2016 | archive-date = 26 August 2016 | archive-url = https://web.archive.org/web/20160826163615/http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Metoclopramide_31/WC500160356.pdf | url-status = dead }}

Metoclopramide has long been used in all stages of pregnancy with no evidence of harm to the mother or foetus.{{cite book| vauthors = Briggs GG, Freeman RK, Yaffe SJ | url =https://archive.org/details/drugsinpregnancy0008brig| url-access = registration | title = Drugs in Pregnancy and Lactation| pages = [https://archive.org/details/drugsinpregnancy0008brig/page/1197 1197]–1200| edition = 8th| location = Philadelphia| publisher = Lippincott Williams & Wilkins| year = 2008| isbn = 978-0-7817-7876-3| access-date = 11 June 2009}} A large cohort study of babies born to Israeli women exposed to metoclopramide during pregnancy found no evidence that the drug increases the risk of congenital malformations, low birth weight, preterm birth, or perinatal mortality.{{cite journal | vauthors = Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A | title = The safety of metoclopramide use in the first trimester of pregnancy | journal = The New England Journal of Medicine | volume = 360 | issue = 24 | pages = 2528–2535 | date = June 2009 | pmid = 19516033 | doi = 10.1056/NEJMoa0807154 | doi-access = free }} A large cohort study in Denmark found, in addition, no association between metoclopramide exposure and miscarriage.{{cite journal | vauthors = Pasternak B, Svanström H, Mølgaard-Nielsen D, Melbye M, Hviid A | title = Metoclopramide in pregnancy and risk of major congenital malformations and fetal death | journal = JAMA | volume = 310 | issue = 15 | pages = 1601–1611 | date = October 2013 | pmid = 24129464 | doi = 10.1001/jama.2013.278343 | doi-access = free }} Metoclopramide is excreted into milk.

A systematic review found a wide range of reported outcomes for the treatment of gastroesophageal reflux disease (GERD) in infants rating the evidence as "poor" and "inconclusive" for safety and efficacy for the treatment of GERD in infants.{{cite journal | vauthors = Hibbs AM, Lorch SA | title = Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review | journal = Pediatrics | volume = 118 | issue = 2 | pages = 746–752 | date = August 2006 | pmid = 16882832 | doi = 10.1542/peds.2005-2664 | s2cid = 21568481 }}

Image:Metoclopramide ampule.jpg of metoclopramide]]

Common adverse drug reactions (ADRs) associated with metoclopramide therapy include restlessness (akathisia), and focal dystonia. Infrequent ADRs include hypertension, hypotension, hyperprolactinaemia leading to galactorrhea, headache, and extrapyramidal effects such as oculogyric crisis.

Metoclopramide may be the most common cause of drug-induced movement disorders. The risk of extrapyramidal effects is increased in people under 20 years of age, and with high-dose or prolonged therapy. Tardive dyskinesia may be persistent and irreversible in some people. The majority of reports of tardive dyskinesia occur in people who have used metoclopramide for more than three months. Consequently, the US Food and Drug Administration (FDA) recommends that metoclopramide be used for short-term treatment, preferably less than 12 weeks. In 2009, the FDA required all manufacturers of metoclopramide to issue a black box warning regarding the risk of tardive dyskinesia with chronic or high-dose use of the drug.{{cite press release| title = FDA requires boxed warning and risk mitigation strategy for metoclopramide-containing drugs| publisher = U.S. Food and Drug Administration| date = 26 February 2009| url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149533.htm| access-date = 11 June 2009| archive-date = 18 January 2017| archive-url = https://web.archive.org/web/20170118093039/http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm149533.htm| url-status = live}}

{{cite web| url =http://www.webmd.com/digestive-disorders/news/20090227/metoclopramide-drugs-get-black-box-warning| title =Lay Summary – WebMD| access-date =11 June 2009| archive-date =18 January 2017| archive-url =https://web.archive.org/web/20170118093039/http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm149533.htm| url-status =live}}

Dystonic reactions may be treated with benzatropine, diphenhydramine, trihexyphenidyl, or procyclidine. Symptoms usually subside with intramuscularly injected diphenhydramine. Agents in the benzodiazepine class of drugs may be helpful, but benefits are usually modest, and the side effects of sedation and weakness can be problematic.{{cite book | vauthors = Olanow C, Schapira AV | chapter = Chapter 372. Parkinson's Disease and Other Movement Disorders. | veditors = Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J | title = Harrison's Principles of Internal Medicine | edition = 18th | location = New York, NY | publisher = McGraw-Hill | date = 2012 }}

In some cases, the akathisia effects of metoclopramide are directly related to the infusion rate when the drug is administered intravenously. Side effects were usually seen in the first 15 minutes after administering the dose of metoclopramide.{{cite book |vauthors=Dobbs MR |title=Clinical Neurotoxicology E-Book: Syndromes, Substances, Environments |date=2009 |publisher=Elsevier Health Sciences |isbn=978-0-323-07099-7 |page=393 |url=https://books.google.com/books?id=vOTM-_jGQ50C&dq=infusion+rate+metoclopramide&pg=PA393 |access-date=19 March 2023 |archive-date=25 July 2024 |archive-url=https://web.archive.org/web/20240725102457/https://books.google.com/books?id=vOTM-_jGQ50C&dq=infusion+rate+metoclopramide&pg=PA393#v=onepage&q=infusion%20rate%20metoclopramide&f=false |url-status=live }}

Withdrawal effects were reported for a female taking metoclopramide for about six months. The adverse symptoms oscillated between akinesian and akathisian, including amenorrhea, and appeared like secondary parkinsonism. Adverse effects remained a year after the metoclopramide had been gradually withdrawn.Noll AM, Pinsky D (June 1991). “Withdrawal Effects of Metoclopramide". The Western Journal of Medicine. 154 (6): 726-728. PMC1002885

Diabetes, age, and female gender are risk factors that increase the likelihood of experiencing a neuropsychiatric side effect of metoclopramide.

• Panic disorder{{cite journal | vauthors = Isola S, Adams N | title = Metoclopramide | journal = Statpearls | date = 2020 | pmid = 30137802 }}
• Major depressive disorder
• Agoraphobia
• Agranulocytosis, supraventricular tachycardia, hyperaldosteronism, neuroleptic malignant syndrome, akathisia and tardive dyskinesia.
• Methaemoglobinaemia*

Metoclopramide appears to bind to dopamine D₂ receptors with nanomolar affinity (K_i = 28.8 nM),{{cite journal | vauthors = Matsui A, Matsuo H, Takanaga H, Sasaki S, Maeda M, Sawada Y | title = Prediction of catalepsies induced by amiodarone, aprindine and procaine: similarity in conformation of diethylaminoethyl side chain | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 287 | issue = 2 | pages = 725–732 | date = November 1998 | doi = 10.1016/S0022-3565(24)37850-4 | pmid = 9808703 | url = http://jpet.aspetjournals.org/content/287/2/725.full.pdf | access-date = 21 January 2018 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828172115/https://jpet.aspetjournals.org/content/287/2/725 | url-status = live }} where it is a receptor antagonist, and is also a mixed 5-HT₃ receptor antagonist/5-HT₄ receptor agonist.{{cite journal | vauthors = Surawski RJ, Quinn DK | title = Metoclopramide and homicidal ideation: a case report and literature review | journal = Psychosomatics | volume = 52 | issue = 5 | pages = 403–409 | date = 2011 | pmid = 21907057 | doi = 10.1016/j.psym.2011.02.001 }}

The antiemetic action of metoclopramide is due to its antagonist activity at D₂ receptors in the chemoreceptor trigger zone in the brain — this action prevents nausea and vomiting triggered by most stimuli.{{cite book| vauthors = Rang HP, Dale MM, Ritter JM, Moore PK | title = Pharmacology| edition = 5th | location = Edinburgh| publisher = Churchill Livingstone| year = 2003| isbn = 978-0-443-07145-4}} At higher doses, 5-HT₃ antagonist activity may also contribute to the antiemetic effect.{{Failed verification|date=March 2019}}

The gastroprokinetic activity of metoclopramide is mediated by muscarinic activity, D₂ receptor antagonist activity, and 5-HT₄ receptor agonist activity.{{cite book| editor = Sweetman S.| title = Martindale: The Complete Drug Reference| edition = 34th| location = London| publisher = Pharmaceutical Press| year = 2004| isbn = 978-0-85369-550-9}}{{cite journal | vauthors = Tonini M, Candura SM, Messori E, Rizzi CA | title = Therapeutic potential of drugs with mixed 5-HT4 agonist/5-HT3 antagonist action in the control of emesis | journal = Pharmacological Research | volume = 31 | issue = 5 | pages = 257–260 | date = May 1995 | pmid = 7479521 | doi = 10.1016/1043-6618(95)80029-8 }} The gastroprokinetic effect itself may also contribute to the antiemetic effect.{{Citation needed|reason=This claim needs a reliable source|date=March 2019}} Metoclopramide also increases the tone of the lower esophageal sphincter.{{cite book| veditors = Feldman M, Friedman LS, Brandt LJ | chapter = Ch. 43: Gastroesophageal Reflux Disease| title = Sleisenger and Fordtran's Gastrointestinal and Liver Disease| edition = 9th| location = Philadelphia| publisher = Saunders| year = 2010| isbn = 978-1-4160-6189-2}}

Metoclopramide might influence mood because of its antagonistic blockade on 5-HT₃ and agonistic (activating) action on 5-HT₄.

While muscarinic receptors affect gastrointestinal motility, metoclopramide’s prokinetic effects are not primarily due to direct muscarinic receptor activity. Instead, they result from its actions on 5-HT4 and D2 receptors.

CYP2D6 metabolizes metoclopramide, a reversible inhibitor, but not inactivator, of CYP2D6. The major metabolites of metoclopramide are N-hydroxylation and N-deethylation by all common CYP enzymes.{{cite journal | vauthors = Livezey MR, Briggs ED, Bolles AK, Nagy LD, Fujiwara R, Furge LL | title = Metoclopramide is metabolized by CYP2D6 and is a reversible inhibitor, but not inactivator, of CYP2D6 | journal = Xenobiotica; the Fate of Foreign Compounds in Biological Systems | volume = 44 | issue = 4 | pages = 309–319 | date = April 2014 | pmid = 24010633 | pmc = 4059401 | doi = 10.3109/00498254.2013.835885 }}

Metoclopramide is a substituted benzamide; cisapride and mosapride are structurally related.{{cite book | vauthors = Fischer J, Gere A | chapter = Timing of Analog Research in Medicinal Chemistry. Chapter 6 | title = Drug Discovery and Development | volume = 1 | veditors = Chorghade MS | publisher = John Wiley & Sons | date = 2006 | isbn = 978-0-471-78009-0 | chapter-url = https://books.google.com/books?id=Bu5IHnBxjxwC&pg=PA203 | pages = 203–205 | access-date = 25 August 2016 | archive-date = 13 January 2023 | archive-url = https://web.archive.org/web/20230113012354/https://books.google.com/books?id=Bu5IHnBxjxwC&pg=PA203 | url-status = live }}

Metoclopramide was first described by Louis Justin-Besançon and Charles Laville in 1964, while working to improve the anti-dysrhythmic properties of procainamide.{{cite book|vauthors=Sneader W|title=Drug Discovery: A History|url=https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA130|date=31 October 2005|publisher=John Wiley & Sons|isbn=978-0-470-01552-0|pages=205–|access-date=24 August 2016|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113012354/https://books.google.com/books?id=Cb6BOkj9fK4C&pg=PA130|url-status=live}}{{cite journal | vauthors = Sanger GJ | title = Translating 5-HT receptor pharmacology | journal = Neurogastroenterology and Motility | volume = 21 | issue = 12 | pages = 1235–1238 | date = December 2009 | pmid = 19906028 | doi = 10.1111/j.1365-2982.2009.01425.x | s2cid = 35544028 | doi-access = free }}{{cite journal | vauthors = Justin-Besancon L, Laville C | title = [Antiemetic Action of Metoclopramide with Respect to Apomorphine and Hydergine] | language = fr | journal = Comptes Rendus des Séances de la Société de Biologie et de ses Filiales | volume = 158 | pages = 723–727 | year = 1964 | pmid = 14186927 }}{{Cite book |doi = 10.1159/000071415|chapter = Metoclopramide for the Control of Postoperative Nausea and Vomiting|title = Antiemetic Therapy|pages = 161–168|year = 2003| vauthors = Henzi I, Tramèr MR | veditors = Donnerer J |isbn = 3-8055-7547-5}} That research project also produced the product sulpiride. The first clinical trials were published by Tourneu et al. in 1964 and by Boisson and Albot in 1966. Justin-Besançon and Laville worked for Laboratoires Delagrange and that company introduced the drug Primperan in 1964.{{cite book | vauthors = Landry Y | title = Petite histoire des médicaments: De l'Antiquité à nos jours. | publisher = Dunod | date = 2011 | isbn = 978-2-10-057130-7 | url = https://books.google.com/books?id=MgLrCgAAQBAJ&pg=PT182 | page = 182 | access-date = 24 August 2016 | archive-date = 13 January 2023 | archive-url = https://web.archive.org/web/20230113012356/https://books.google.com/books?id=MgLrCgAAQBAJ&pg=PT182 | url-status = live }}{{cite journal | vauthors = Lefebvre T, Raynal C | title = La mystérieuse bonbonne des Laboratoires Delagrange [Q265, Usage des bonbonnes]. | journal = Revue d'Histoire de la Pharmacie | year = 2007 | volume = 94 | issue = 353 | pages = 160–162 | url = http://www.persee.fr/doc/pharm_0035-2349_2007_num_94_353_6121 | access-date = 24 August 2016 | archive-date = 10 May 2017 | archive-url = https://web.archive.org/web/20170510121243/http://www.persee.fr/doc/pharm_0035-2349_2007_num_94_353_6121 | url-status = live }} Laboratoires Delagrange was acquired by Synthelabo in 1991{{cite web | vauthors = Conard D | agency = Les Echos | date = 17 October 1991 | url = http://www.lesechos.fr/17/10/1991/LesEchos/15996-035-ECH_synthelabo-rachete-les-laboratoires-delagrange.htm | title = Synthélabo rachète les laboratoires Delagrange | publisher = Lesechos.fr | access-date = 24 August 2016 | archive-date = 16 October 2016 | archive-url = https://web.archive.org/web/20161016193610/http://www.lesechos.fr/17/10/1991/LesEchos/15996-035-ECH_synthelabo-rachete-les-laboratoires-delagrange.htm | url-status = live }}{{cite web|url=http://data.bnf.fr/12198004/laboratoires_delagrange/|title=Laboratoires Delagrange (1932) - Organisation - Resources from the BnF|publisher=Data.bnf.fr|access-date=21 January 2018|archive-date=21 November 2017|archive-url=https://web.archive.org/web/20171121004926/http://data.bnf.fr/12198004/laboratoires_delagrange/|url-status=live}} which eventually became part of Sanofi.{{cite web | vauthors = Meek T | work = PMLiVE | date = 24 May 2013 | url = http://www.pmlive.com/pharma_news/a_look_back_at_sanofis_merger_with_synthelabo_477146 | title = A look back at Sanofi's merger with Synthélabo | publisher = Pmlive.com | access-date = 24 August 2016 | archive-date = 26 August 2016 | archive-url = https://web.archive.org/web/20160826030703/http://www.pmlive.com/pharma_news/a_look_back_at_sanofis_merger_with_synthelabo_477146 | url-status = live }}

A.H. Robins introduced the drug in the US under the brand name Reglan in 1979{{cite book | chapter = Metoclopramide hydrochloride | title = Pharmaceutical Manufacturing Encyclopedia | edition = 3rd | volume = 1-4 | publisher = Elsevier | date = 2013 | isbn = 978-0-8155-1856-3 | chapter-url = https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2109-IA164 | pages = 179m | access-date = 24 August 2016 | archive-date = 13 January 2023 | archive-url = https://web.archive.org/web/20230113012356/https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA2109-IA164 | url-status = live }} as an injectable{{cite web | publisher = U.S. Food and Drug Administration | url = http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=017862 | title = New Drug Application (NDA): 017862 - Approval history - Hikma Metoclopramide Hydrochloride | access-date = 8 March 2022 | archive-date = 25 July 2024 | archive-url = https://web.archive.org/web/20240725102408/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=017862 | url-status = live }} and an oral form was approved in 1980.{{cite web | work = U.S. Food and Drug Administration | url = http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=017854 | title = New Drug Application (NDA): 017854: Approval history - Ani Pharms Metoclopramide Hydrochloride | access-date = 8 March 2022 | archive-date = 8 March 2022 | archive-url = https://web.archive.org/web/20220308045135/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=017854 | url-status = live }} in 1989 A.H. Robins was acquired by American Home Products,{{cite web|url=http://www.vahistorical.org/collections-and-resources/how-we-can-help-your-research/researcher-resources/finding-aids/ah-robins|title= Virginia Historical Society A Guide to the A. H. Robins Company Records, 1885–2004.|website=Vahistorical.org|access-date=21 January 2018|archive-url=https://web.archive.org/web/20171201042028/http://www.vahistorical.org/collections-and-resources/how-we-can-help-your-research/researcher-resources/finding-aids/ah-robins|archive-date=1 December 2017|url-status=dead}} which changed its name to Wyeth in 2002.{{cite web | vauthors = Petersen M | work = The New York Times | date = 11 March 2002 | url = https://www.nytimes.com/2002/03/11/business/american-home-is-changing-name-to-wyeth.html | title = American Home Is Changing Name to Wyeth | access-date = 19 February 2017 | archive-date = 10 May 2017 | archive-url = https://web.archive.org/web/20170510121347/http://www.nytimes.com/2002/03/11/business/american-home-is-changing-name-to-wyeth.html | url-status = live }}

The drugs were initially used to control nausea for people with severe headaches or migraines, and later used for nausea caused by radiation therapy and chemotherapy, and later yet for treating nausea caused by anesthesia. In the US the injectable form was labelled for chemotherapy-induced nausea and the oral form was eventually labelled for gastroesophageal reflux disease.

It became widely used in the 1980s, becoming the most commonly used drug to treat anesthesia-induced nausea and for treating gastritis in emergency rooms.{{cite web|url=http://epmonthly.com/article/all-about-metoclopramide-reglan/|title=All About Metoclopramide (Reglan)|work=Emergency Physicians Monthly|publisher=EPMonthly.com|date=15 August 2014|access-date=21 January 2018|archive-date=21 January 2018|archive-url=https://web.archive.org/web/20180121184810/http://epmonthly.com/article/all-about-metoclopramide-reglan/|url-status=live}}

The first generics were introduced in 1985.{{cite web | author = Staff | work = The Pink Sheet | date = 29 September 1986 | url = https://pink.pharmamedtechbi.com/PS010783/FDAs-ORAL-VERAPAMIL-ANDA-APPROVALS-ON-EVE-OF-EXCLUSIVITY-EXPIRATION-PIT-FIVE-GENERIC-PRODUCTS-v-CALAN-ISOPTIN-INDERAL-REGLAN-INDICATIONS-NO-LONGER-EXCLUSIVE | title = FDA's Oral Verapamil ANDA Approvals on Eve of Exclusivity Expiration Pit Five Generic Products V. Calan, Isoptin; Inderal, Reglan Indications No Longer Exclusive | archive-url = https://web.archive.org/web/20170510105605/https://pink.pharmamedtechbi.com/PS010783/FDAs-ORAL-VERAPAMIL-ANDA-APPROVALS-ON-EVE-OF-EXCLUSIVITY-EXPIRATION-PIT-FIVE-GENERIC-PRODUCTS-v-CALAN-ISOPTIN-INDERAL-REGLAN-INDICATIONS-NO-LONGER-EXCLUSIVE | archive-date= 10 May 2017 }}{{cite web | publisher = U.S. Food and Drug Administration | url = https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=070184 | work = Abbreviated New Drug Application (ANDA): 070184 | title = TEVA Metoclopramide Hydrochloride | access-date = 7 March 2022 | archive-date = 25 July 2024 | archive-url = https://web.archive.org/web/20240725102355/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=070184 | url-status = live }}

In the early 1980s signs began to emerge in pharmacovigilance studies from Sweden that the drug was causing tardive dyskinesia in some patients.{{cite journal | vauthors = Wiholm BE, Mortimer O, Boethius G, Häggström JE | title = Tardive dyskinesia associated with metoclopramide | journal = British Medical Journal | volume = 288 | issue = 6416 | pages = 545–547 | date = February 1984 | pmid = 6421373 | pmc = 1444584 | doi = 10.1136/bmj.288.6416.545 }} The FDA required a warning about tardive dyskinesia to be added to the drug label in 1985 stating that: "tardive dyskinesia . . . may develop in patients treated with metoclopramide,” and warned against use longer than 12 weeks, as that was how long the drug has been tested.{{cite journal | vauthors = Stoddart A | title = Missing After Mensing: A Remedy for Generic Drug Consumers. | journal = Boston College Law Review | date = 2012 | volume = 53 | pages = 1967–2001 | url = http://lawdigitalcommons.bc.edu/bclr/vol53/iss5/9 | access-date = 25 August 2016 | archive-date = 14 December 2016 | archive-url = https://web.archive.org/web/20161214131835/http://lawdigitalcommons.bc.edu/bclr/vol53/iss5/9/ | url-status = live }}{{cite web | vauthors = Casey S | work = Law360 | date = 24 October 2012 | url = http://www.law360.com/articles/388965/generic-pharmaceutical-liability-challenges-and-changes | title = Generic Pharmaceutical Liability: Challenges And Changes | access-date = 25 August 2016 | archive-date = 28 April 2021 | archive-url = https://web.archive.org/web/20210428161001/http://www.law360.com/articles/388965/generic-pharmaceutical-liability-challenges-and-changes | url-status = live }}com In 2009 the FDA required that a black box warning be added to the label.{{cite journal | vauthors = Rao AS, Camilleri M | title = Review article: metoclopramide and tardive dyskinesia | journal = Alimentary Pharmacology & Therapeutics | volume = 31 | issue = 1 | pages = 11–19 | date = January 2010 | pmid = 19886950 | doi = 10.1111/j.1365-2036.2009.04189.x | s2cid = 22847205 | doi-access = free }}

The emergence of this severe side effect led to a wave of product liability litigation against generic manufacturers as well as Wyeth.{{cite journal | vauthors = Noah L | url = http://www.americanbar.org/content/dam/aba/publications/tort_insurance_law_journal/tips_vol45_no3_4_Noah.authcheckdam.pdf | title = Adding Insult to Injury: Paying For Harms Caused by a Competitor's Copycat Product | journal = Tort Trial & Insurance Practice Law Journal | date =Spring–Summer 2010 | volume = 45 | issue = 3–4 | pages = 673–695 | jstor = 41059447 | access-date = 25 August 2016 | archive-date = 11 October 2016 | archive-url = https://web.archive.org/web/20161011045916/http://www.americanbar.org/content/dam/aba/publications/tort_insurance_law_journal/tips_vol45_no3_4_Noah.authcheckdam.pdf | url-status = dead }} The litigation was complicated since there was a lack of clarity in jurisdiction between state laws, where product liability is determined, and federal law, which determines how drugs are labelled, as well as between generics companies, which had no control over labelling, and the originator company, which did.{{cite web | vauthors = Rothschild E | work = Pepper Hamilton LLP's Insight Center | date = 16 March 2016 | url = http://www.pepperlaw.com/publications/calif-asks-innovator-drug-brands-to-do-the-impossible-2016-03-16/ | title = Calif. Asks Innovator Drug Brands To Do The Impossible | archive-url = https://web.archive.org/web/20160805025349/http://www.pepperlaw.com/publications/calif-asks-innovator-drug-brands-to-do-the-impossible-2016-03-16/ | archive-date=5 August 2016 }} The litigation yielded at least two important cases. In Conte v. Wyeth in the California state courts, the claims of the plaintiff against the generic companies Pliva, Teva, and Purepac that had sold the drugs that the plaintiff actually took, and the claims against Wyeth, whose product the plaintiff never took, were all dismissed by the trial court, but the case was appealed, and in 2008 the appellate court upheld the dismissal of the cases against the generic companies, but reversed on Wyeth, allowing the case against Wyeth to proceed.{{cite court|litigants= Conte v. Wyeth, Inc.|vol= A116707, A117353|reporter= |opinion= |pinpoint= |court= Court of Appeal, First District, Division 3, California.|date= |url= https://caselaw.findlaw.com/ca-court-of-appeal/1114587.html|postscript= |access-date= |quote= |archive-url= https://web.archive.org/web/20171201044900/http://caselaw.findlaw.com/ca-court-of-appeal/1114587.html|url-status= live}} This established an "innovator liability" or "pioneer liability" for pharmaceutical companies. The precedent was not widely followed in California nor in other states. Litigation over the same issues related to metoclopramide also reached the US Supreme Court in Pliva, Inc. v. Mensing,{{cite court |litigants= PLIVA, Inc. v. Mensing |vol= |reporter= |opinion= |pinpoint= |court= U.S. Supreme Court |date= 23 June 2011 |url= http://www.scotusblog.com/case-files/cases/pliva-inc-v-mensing/ |access-date= 21 January 2018 |quote= |postscript= |archive-url= https://web.archive.org/web/20210314163154/https://www.scotusblog.com/case-files/cases/pliva-inc-v-mensing/ |url-status= live }} in which the court held in 2011 that generic companies cannot be held liable for information, or the lack of information, on the originator's label.{{cite web | vauthors = Liptak A | work = The New York Times | date = 23 June 2011 | url = https://www.nytimes.com/2011/06/24/business/24bizcourt.html | title = Drug Makers Win Two Supreme Court Decisions | access-date = 19 February 2017 | archive-date = 27 April 2021 | archive-url = https://web.archive.org/web/20210427113404/https://www.nytimes.com/2011/06/24/business/24bizcourt.html | url-status = live }} As of August 2015 there were about 5000 suits pending across the US and efforts to consolidate them into a class action had failed.{{citation needed|date=May 2019}}

Shortly following the Pliva decision, the FDA proposed a rule change that would allow generics manufacturers to update the label if the originating drug had been withdrawn from the market for reasons other than safety.{{cite web|url=http://www.today.com/news/fda-moves-make-generic-drugmakers-more-accountable-8C11545187|title=FDA moves to make generic drugmakers more accountable|vauthors=Rossen J, Patel A|website=Today.com|date=8 November 2013|access-date=21 January 2018|archive-date=1 December 2017|archive-url=https://web.archive.org/web/20171201131456/https://www.today.com/news/fda-moves-make-generic-drugmakers-more-accountable-8C11545187|url-status=live}} As of May 2016 the rule, which turned out to be controversial since it would open generic companies to product liability suits, was still not finalized, and the FDA had stated the final rule would be issued in April 2017.{{cite web | vauthors = Silverman E | date = 19 May 2016 | url = https://www.statnews.com/pharmalot/2016/05/19/fda-generic-drugs-safety/ | title = FDA delays rule to allow generic drug makers to change labels | work = Pharmalot | publisher = Statnews.com | access-date = 21 January 2018 | archive-date = 1 December 2017 | archive-url = https://web.archive.org/web/20171201041520/https://www.statnews.com/pharmalot/2016/05/19/fda-generic-drugs-safety/ | url-status = live }} The FDA issued a draft guidance for generic companies to update labels in July 2016.{{cite web | vauthors = Brennan Z | work = Regulatory Focus | date = 8 July 2016 | url = http://raps.org/Regulatory-Focus/News/2016/07/08/25292/Generic-Drug-Labels-FDA-Offers-Draft-Guidance-on-Updates-After-Reference-Products-are-Withdrawn/ | title = Generic Drug Labels: FDA Offers Draft Guidance on Updates After Reference Products are Withdrawn | access-date = 25 August 2016 | archive-date = 11 August 2016 | archive-url = https://web.archive.org/web/20160811035941/http://www.raps.org/Regulatory-Focus/News/2016/07/08/25292/Generic-Drug-Labels-FDA-Offers-Draft-Guidance-on-Updates-After-Reference-Products-are-Withdrawn/ | url-status = live }}

Metoclopramide is commonly used to prevent vomiting in cats and dogs. It is also used as a gut stimulant in rabbits.{{cite web | vauthors = Mikota SK, Plumb DC |title=Metoclopramide HCl |work=The Elephant Formulary |date=June 2003 |publisher=Elephant Care International |url=http://www.elephantcare.org/Drugs/metoclop.htm |url-status=dead |archive-url=https://web.archive.org/web/20031229032933/http://www.elephantcare.org/Drugs/metoclop.htm |archive-date=29 December 2003 }}

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