Editing Domperidone

{{Short description|Peripheral D2 receptor antagonist}}
{{Distinguish|Droperidol}}
{{Use dmy dates|date=June 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 458442916
| image = Domperidone 2D structure.svg
| image_class = skin-invert-image
| width = 250
| alt = 
| image2 = Domperidone-from-xtal-3D-bs-17.png
| image_class2 = bg-transparent
| width2 = 250
| alt2 =

<!-- Clinical data -->
| pronounce = 
| tradename = Motilium, others
| Drugs.com = {{drugs.com|CONS|domperidone}}
| MedlinePlus = 
| DailyMedID = <!-- DailyMed may use generic or brand name (generic name preferred) -->
| pregnancy_AU = B2
| pregnancy_AU_comment = <ref>{{cite web | title=Motilium Product Information | website=[[Therapeutic Goods Administration]] (TGA) | date=10 June 2024 | url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2023-PI-02610-1 | access-date=10 June 2024}}</ref>
| pregnancy_category = 
| routes_of_administration = [[Oral administration|By mouth]], [[rectal administration|rectal]]<ref name="mechanismforantiemetic"/>
| class = [[Dopamine antagonist|D<sub>2</sub> receptor antagonist]]; [[Prolactin releaser]]
| ATC_prefix = A03
| ATC_suffix = FA03
| ATC_supplemental = {{ATCvet|P51|DX06}}

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = 
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment = 
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Motilium product information | website=[[Health Canada]] | date=7 January 2002 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=10691 | access-date=10 June 2024}}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment = 
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment = 
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Motilium Summary of Product Characteristics (SmPC) | website=(emc) | date=11 March 2024 | url=https://www.medicines.org.uk/emc/product/4177/smpc | access-date=10 June 2024}}</ref>
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_US_comment = 
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | title=Motilium referral | website=[[European Medicines Agency]] (EMA) | date=31 October 2000 | url=https://www.ema.europa.eu/en/medicines/human/referrals/motilium | access-date=10 June 2024}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment = 
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = Oral: 13–17%<ref name="mechanismforantiemetic"/><ref name="Rose2004">{{cite book|vauthors=Rose S|title=Gastrointestinal and Hepatobiliary Pathophysiology|url=https://books.google.com/books?id=1W0JYuzTZsAC&pg=PA523|date=October 2004|publisher=Hayes Barton Press|isbn=978-1-59377-181-2|pages=523–}}{{Dead link|date=August 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><br />Intramuscular: 90%<ref name="mechanismforantiemetic"/>
| protein_bound = ~92%<ref name="mechanismforantiemetic"/>
| metabolism = [[Liver|Hepatic]] ([[CYP3A4]]/[[CYP3A5|5]]) and [[intestine|intestinal]] ([[first pass effect|first-pass]])<ref name="mechanismforantiemetic"/><ref name="SimardMichaud2008">{{cite journal | vauthors = Simard C, Michaud V, Gibbs B, Massé R, Lessard E, Turgeon J | title = Identification of the cytochrome P450 enzymes involved in the metabolism of domperidone | journal = Xenobiotica; the Fate of Foreign Compounds in Biological Systems | volume = 34 | issue = 11–12 | pages = 1013–1023 | year = 2008 | pmid = 15801545 | doi = 10.1080/00498250400015301 | s2cid = 27426219 }}</ref>
| metabolites = All inactive<ref name="mechanismforantiemetic"/><ref name="SimardMichaud2008" />
| onset = 30–60 minutes<ref name="NHS-Domperidone">{{Cite web|url=https://www.nhs.uk/medicines/domperidone/|title = Domperidone: Anti-sickness medicine used to treat nausea and vomiting|date = 7 January 2020}}</ref>
| elimination_half-life = 7–9 hours<ref name="EMC-Domperidone" /><ref name="mechanismforantiemetic"/><ref name="Rose2004" />
| duration_of_action = 
| excretion = [[Feces]]: 66%<ref name="mechanismforantiemetic"/><br />[[Urine]]: 32%<ref name="mechanismforantiemetic"/><br />[[Breast milk]]: small quantities<ref name="mechanismforantiemetic"/>

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 57808-66-9
| CAS_supplemental = 
| PubChem = 3151
| IUPHAR_ligand = 965
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01184
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3039
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 5587267Z69
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01745
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 31515
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 219916
| NIAID_ChemDB = 
| PDB_ligand = 
| synonyms = R-33812; R33812; KW-5338; KW5338; NSC-299589; NSC299589

<!-- Chemical and physical data -->
| IUPAC_name = 5-Chloro-1-(1-[3-(2-oxo-2,3-dihydro-1''H''-benzo[''d'']imidazol-1-yl)propyl]piperidin-4-yl)-1''H''-benzo[''d'']imidazol-2(3''H'')-one
| C=22 | H=24 | Cl=1 | N=5 | O=2
| SMILES = Clc1cc2c(cc1)N(C(=O)N2)C5CCN(CCCN4c3ccccc3NC4=O)CC5
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C22H24ClN5O2/c23-15-6-7-20-18(14-15)25-22(30)28(20)16-8-12-26(13-9-16)10-3-11-27-19-5-2-1-4-17(19)24-21(27)29/h1-2,4-7,14,16H,3,8-13H2,(H,24,29)(H,25,30)
| StdInChI_comment = 
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FGXWKSZFVQUSTL-UHFFFAOYSA-N
| density = 
| density_notes = 
| melting_point = 242.5
| melting_high = 
| melting_notes = 
| boiling_point = 
| boiling_notes = 
| solubility = 
| sol_units = 
| specific_rotation = 
}}

<!-- Definition and medical uses -->
'''Domperidone''', sold under the brand name '''Motilium''' among others, is a [[dopamine antagonist]] [[medication]] which is used to treat [[nausea]] and [[vomiting]] and certain [[gastrointestinal symptom|gastrointestinal problem]]s like [[gastroparesis]] (delayed [[gastric emptying]]). It raises the level of [[prolactin]] in the human body and is used [[off label]] to induce and promote [[lactation|breast milk production]].<ref name="mechanismforantiemetic">{{cite journal | vauthors = Reddymasu SC, Soykan I, McCallum RW | title = Domperidone: review of pharmacology and clinical applications in gastroenterology | journal = The American Journal of Gastroenterology | volume = 102 | issue = 9 | pages = 2036–2045 | date = September 2007 | pmid = 17488253 | doi = 10.1111/j.1572-0241.2007.01255.x | s2cid = 22575456 }}</ref><ref name="pmid10332535">{{cite journal | vauthors = Barone JA | title = Domperidone: a peripherally acting dopamine2-receptor antagonist | journal = The Annals of Pharmacotherapy | volume = 33 | issue = 4 | pages = 429–440 | date = April 1999 | pmid = 10332535 | doi = 10.1345/aph.18003 | s2cid = 39279569 }}</ref> It may be taken [[oral administration|by mouth]] or [[rectal]]ly.<ref name="mechanismforantiemetic"/><ref name="ema" /><ref name="mhra">{{Cite web |url=http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con076114.pdf |title=Motilium INSTANTS PL 13249/0028 |date=23 February 2010 |publisher=[[Medicines and Healthcare products Regulatory Agency]] |access-date=31 October 2014 |archive-url=https://web.archive.org/web/20141213170157/http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con076114.pdf |archive-date=13 December 2014 |url-status=dead  }}</ref>

<!-- Side effects and mechanism -->
[[Side effect]]s may include [[headache]], anxiety, [[dry mouth]], [[abdominal cramp]]s, [[diarrhea]], and [[hyperprolactinemia|elevated prolactin level]]s.<ref name=BNF79>{{cite book |title=BNF 79 : March 2020. |date=2020 |publisher=Royal Pharmaceutical Society |location=London |isbn=9780857113658|page=444}}</ref><ref name="mechanismforantiemetic"/><ref name="pmid10332535" /><ref name="Henderson2003">{{cite journal | vauthors = Henderson A | title = Domperidone. Discovering new choices for lactating mothers | journal = AWHONN Lifelines | volume = 7 | issue = 1 | pages = 54–60 | year = 2003 | pmid = 12674062 | doi = 10.1177/1091592303251726 }}</ref> Secondary to increased prolactin levels, [[breast disorder|breast changes]], [[galactorrhea|milk outflow]], [[menstrual disorder|menstrual irregularities]], and [[hypogonadism]] can occur.<ref name="mechanismforantiemetic"/><ref name="pmid10332535" /><ref name="Henderson2003" /> Domperidone may also cause [[QT prolongation]] and has rarely been associated with serious [[cardiac complication]]s such as [[sudden cardiac death]].<ref name="pmid26649742" /><ref name="pmid20394569" /><ref name="pmid24147629" /><ref name="pmid26117678" /> However, the risks are small and occur more with high doses.<ref name="pmid26117678" /><ref name="MarziWeitz2015" /> Domperidone acts as a [[peripherally selective drug|peripherally selective]] [[receptor antagonist|antagonist]] of the [[dopamine]] [[D2 receptor|D<sub>2</sub>]] and [[D3 receptor|D<sub>3</sub> receptor]]s.<ref name="mechanismforantiemetic"/><ref name="pmid10332535" /> Due to its low entry into the [[brain]], the side effects of domperidone are different from those of other dopamine receptor antagonists like [[metoclopramide]] and it produces little in the way of [[central nervous system]] adverse effects.<ref name="mechanismforantiemetic"/><ref name="pmid10332535"/> However, domperidone can nonetheless increase prolactin levels as the [[pituitary gland]] is outside of the [[blood–brain barrier]].<ref name="pmid25475074">{{cite journal | vauthors = Paul C, Zénut M, Dorut A, Coudoré MA, Vein J, Cardot JM, Balayssac D | title = Use of domperidone as a galactagogue drug: a systematic review of the benefit-risk ratio | journal = Journal of Human Lactation | volume = 31 | issue = 1 | pages = 57–63 | date = February 2015 | pmid = 25475074 | doi = 10.1177/0890334414561265 | s2cid = 7978585 }}</ref>

<!-- History, society, and culture -->
Domperidone was discovered in 1974 and was introduced for medical use in 1979.<ref name="pmid18507654" /><ref name="dd" /><ref name="WilliamAndrewPublishing2013" /> It was developed by [[Janssen Pharmaceutica]].<ref name="pmid18507654" /><ref name="dd" /> Domperidone is available [[over-the-counter]] in many countries, for instance in Europe and elsewhere throughout the world.<ref name="FaisVermiglio2015" /><ref name="mechanismforantiemetic"/> It is not approved for use in the United States.<ref name="FDA 20231212" /><ref name="pmid15451832" /><ref name="mechanismforantiemetic"/> However, it is available in the United States for people with severe and treatment-refractory gastrointestinal motility problems under an [[expanded access]] individual-patient [[investigational new drug]] application.<ref name="FDA 20231212">{{cite web | url=https://www.fda.gov/drugs/investigational-new-drug-ind-application/how-request-domperidone-expanded-access-use | archive-url=https://web.archive.org/web/20190518202956/https://www.fda.gov/drugs/investigational-new-drug-ind-application/how-request-domperidone-expanded-access-use | url-status=dead | archive-date=18 May 2019 | title=How to Request Domperidone for Expanded Access Use | website=U.S. [[Food and Drug Administration]] (FDA) | date=12 December 2023 }}</ref> An [[structural analog|analogue]] of domperidone called [[deudomperidone]] is under development for potential use in the United States and other countries.<ref name="AdisInsight-Deudomperidone">{{Cite web|url=https://adisinsight.springer.com/drugs/800050807|title=Deudomperidone - CinRx Pharma - AdisInsight}}</ref><ref name="pmid33471485">{{cite journal | vauthors = Heckroth M, Luckett RT, Moser C, Parajuli D, Abell TL | title = Nausea and Vomiting in 2021: A Comprehensive Update | journal = Journal of Clinical Gastroenterology | volume = 55 | issue = 4 | pages = 279–299 | date = April 2021 | pmid = 33471485 | pmc = 7933092 | doi = 10.1097/MCG.0000000000001485 }}</ref><ref name="WoMcCallumGonzalez2021">{{cite book | editor-first = | title = Gastroparesis | vauthors = Wo JM, McCallum RW, Gonzalez Z | chapter = Antiemetic therapy for gastroparesis | date = 2021 | pages = 341–359 | publisher = Elsevier | doi = 10.1016/B978-0-12-818586-5.00025-9 | isbn = 9780128185865| s2cid = 225132800| url = }}</ref>

{{TOC limit}}

==Medical uses==

=== Nausea and vomiting ===
There is some evidence that domperidone has [[antiemetic]] activity.<ref name="mechanismforantiemetic"/> It is recommended by the Canadian Headache Society for treatment of nausea associated with acute [[migraine]].<ref>{{cite journal | vauthors = Worthington I, Pringsheim T, Gawel MJ, Gladstone J, Cooper P, Dilli E, Aube M, Leroux E, Becker WJ | title = Canadian Headache Society Guideline: acute drug therapy for migraine headache | journal = The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques | volume = 40 | issue = 5 Suppl 3 | pages = S1–S80 | date = September 2013 | pmid = 23968886 | doi = 10.1017/S0317167100118943 | doi-access = free }}</ref>

===Gastroparesis===
[[Gastroparesis]] is a medical condition characterised by delayed emptying of the stomach when there is <u>no</u> mechanical [[gastric outlet obstruction]]. Its cause is most commonly [[idiopathic]], a [[diabetes|diabetic]] complication or a result of abdominal surgery. The condition causes nausea, vomiting, [[postprandial|fullness after eating]], early satiety (feeling full before the meal is finished), abdominal pain, and bloating. Domperidone can be used to increase the transit of food through the stomach by increasing [[gastrointestinal]] [[peristalsis]] and hence to treat gastroparesis.<ref name="mechanismforantiemetic"/><ref name="pmid10332535" /> It may be useful in idiopathic and diabetic gastroparesis.<ref>{{cite journal | vauthors = Stevens JE, Jones KL, Rayner CK, Horowitz M | title = Pathophysiology and pharmacotherapy of gastroparesis: current and future perspectives | journal = Expert Opinion on Pharmacotherapy | volume = 14 | issue = 9 | pages = 1171–1186 | date = June 2013 | pmid = 23663133 | doi = 10.1517/14656566.2013.795948 | s2cid = 23526883 }}</ref><ref name="pmid9663360">{{cite journal | vauthors = Silvers D, Kipnes M, Broadstone V, Patterson D, Quigley EM, McCallum R, Leidy NK, Farup C, Liu Y, Joslyn A | title = Domperidone in the management of symptoms of diabetic gastroparesis: efficacy, tolerability, and quality-of-life outcomes in a multicenter controlled trial. DOM-USA-5 Study Group | journal = Clinical Therapeutics | volume = 20 | issue = 3 | pages = 438–453 | year = 1998 | pmid = 9663360 | doi = 10.1016/S0149-2918(98)80054-4 }}</ref> However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate well with relief of symptoms.<ref>{{cite journal | vauthors = Janssen P, Harris MS, Jones M, Masaoka T, Farré R, Törnblom H, Van Oudenhove L, Simrén M, Tack J | title = The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis | journal = The American Journal of Gastroenterology | volume = 108 | issue = 9 | pages = 1382–1391 | date = September 2013 | pmid = 24005344 | doi = 10.1038/ajg.2013.118 | s2cid = 32835351 }}</ref>

===Lactation===
Domperidone is used [[Off-label use|off-label]] in some countries to stimulate [[lactation]] or enhance breast milk production, but, as of December 2023, it is not approved for that purpose in any country, and is not approved for use in humans in the United States.<ref name="FDA 20231212" /><ref name="FDADomperidone">{{cite web |title=Information about Domperidone |website=U.S. [[Food and Drug Administration]] (FDA) |date=12 December 2023 |url=https://www.fda.gov/drugs/information-drug-class/information-about-domperidone |archive-url=https://web.archive.org/web/20231213162326/https://www.fda.gov/drugs/information-drug-class/information-about-domperidone |url-status=dead |archive-date=13 December 2023 |access-date=8 June 2024}} {{PD-notice}}</ref> Domperidone acts as a peripheral [[dopamine]] antagonist and is hypothesized to stimulate [[prolactin]] secretion, with a 2003 study supporting that hypothesis.<ref name="pmid15451832">{{cite journal | vauthors = da Silva OP, Knoppert DC | title = Domperidone for lactating women | journal = CMAJ | volume = 171 | issue = 7 | pages = 725–726 | date = September 2004 | pmid = 15451832 | pmc = 517853 | doi = 10.1503/cmaj.1041054 }}</ref>

A 2018 meta-analysis of five randomized controlled trials found that domperidone resulted in a moderate increase of in breast milk volume for mothers of preterm infants with insufficient milk supply. The analysis also indicated that domperidone was well tolerated with no significant difference in maternal adverse events compared to placebo.<ref name="t992">{{cite journal | vauthors = Grzeskowiak LE, Smithers LG, Amir LH, Grivell RM | title = Domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants: a systematic review and meta-analysis | journal = BJOG | volume = 125 | issue = 11 | pages = 1371–1378 | date = October 2018 | pmid = 29469929 | doi = 10.1111/1471-0528.15177 | publisher = Wiley | hdl = 2440/114203 | hdl-access = free }}</ref> Domperidone has no officially established dosage for increasing milk supply, but most published studies have used 10&nbsp;mg three times daily for 4 to 10 days (30&nbsp;mg per day).<ref name="NIH">{{cite journal |journal=Drugs and Lactation Database |title=Domperidone |publisher=Bethesda (MD): National Institute of Child Health and Human Development |orig-date=2006 |date=15 May 2024 |pmid=30000430 |url=https://www.ncbi.nlm.nih.gov/books/NBK501371/}}</ref>

The US [[Food and Drug Administration]] (FDA) has expressed concerns about serious adverse side effects and concerns about its effectiveness.<ref name="FDADomperidone"/> The FDA identified serious cardiac adverse events associated with domperidone use in lactating individuals, including arrhythmias, cardiac arrest, and sudden death. Additionally, discontinuation or tapering of domperidone has been linked to severe neuropsychiatric adverse events such as agitation, anxiety, and suicidal ideation. Because of these risks, the FDA strongly cautions against the use of domperidone to enhance lactation.<ref name="FDADomperidone"/>

A review by [[Health Canada]] also found a link between the sudden discontinuation or tapering of domperidone when used off-label for lactation, and psychiatric withdrawal events, particularly daily doses greater than the maximum recommended dose of 30&nbsp;mg per day.<ref name="HealthCanada">{{cite web |title=Assessing the Potential Risk of Psychiatric Withdrawal Events when Used for Lactation Stimulation |website=Drug and Health Products Portal |date=8 June 2024 |url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR1691692252806 |access-date=8 June 2024}}</ref> A 2021 study found that postpartum usage of domperidone increased across five Canadian provinces from 2004 and 2017 with usage plateauing in 2011 and a drop in usage after a 2012 Health Canada advisory warning about domperidone.<ref name="e088">{{cite journal | vauthors = Moriello C, Paterson JM, Reynier P, Dahl M, Aibibula W, Fisher A, Gamble JM, Kuo IF, Ronksley PE, Winquist B, Filion KB | title = Off-label postpartum use of domperidone in Canada: a multidatabase cohort study | journal = CMAJ Open | volume = 9 | issue = 2 | pages = E500–E509 | year = 2021 | pmid = 33990364 | doi = 10.9778/cmajo.20200084 | publisher = CMA Joule Inc. | pmc = 8157989 }}</ref>

===Other uses===

====Parkinson's disease====
[[Parkinson's disease]] is a [[neurodegenerative disease|degenerative neurological condition]] where a decrease in [[dopamine]] in the [[brain]] leads to [[muscle rigidity|rigidity]] (stiffness of movement), [[tremor]], and other symptoms and signs. Poor [[gastrointestinal]] function, [[nausea]], and [[vomiting]] are major problems for people with Parkinson's disease because most medications used to treat Parkinson's disease are given [[oral administration|by mouth]]. These [[medication]]s, such as [[levodopa]], can also cause nausea as a [[side effect]]. Furthermore, [[antiemetic|anti-nausea drugs]], such as [[metoclopramide]], which do cross the [[blood–brain barrier]], may worsen the [[extrapyramidal symptom]]s of Parkinson's disease. Domperidone can be used to relieve nausea and gastrointestinal symptoms in Parkinson's disease; it blocks peripheral D<sub>2</sub> receptors but minimally crosses the blood-brain barrier in normal doses, so has no effect on the extrapyramidal symptoms of the disease.<ref name="pmid30361854">{{cite journal | vauthors = Ramprasad C, Douglas JY, Moshiree B | title = Parkinson's Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects | journal = Current Treatment Options in Gastroenterology | volume = 16 | issue = 4 | pages = 489–510 | date = December 2018 | pmid = 30361854 | doi = 10.1007/s11938-018-0201-3 | s2cid = 53104650 }}</ref><ref name="pmid18281732">{{cite journal | vauthors = Lertxundi U, Peral J, Mora O, Domingo-Echaburu S, Martínez-Bengoechea MJ, García-Moncó JC | title = Antidopaminergic therapy for managing comorbidities in patients with Parkinson's disease | journal = American Journal of Health-System Pharmacy | volume = 65 | issue = 5 | pages = 414–419 | date = March 2008 | pmid = 18281732 | doi = 10.2146/ajhp060624 }}</ref><ref name="pmid9108986">{{cite journal | vauthors = Jost WH | title = Gastrointestinal motility problems in patients with Parkinson's disease. Effects of antiparkinsonian treatment and guidelines for management | journal = Drugs & Aging | volume = 10 | issue = 4 | pages = 249–258 | date = April 1997 | pmid = 9108986 | doi = 10.2165/00002512-199710040-00002 | s2cid = 38114001 }}</ref> In addition, domperidone may be useful in the treatment of [[orthostatic hypotension]] caused by [[dopaminergic]] therapy in people with Parkinson's disease.<ref name="BacchiChimKramer2017">{{cite journal | vauthors = Bacchi S, Chim I, Kramer P, Postuma RB | title = Domperidone for Hypotension in Parkinson's Disease: A Systematic Review | journal = J Parkinsons Dis | volume = 7 | issue = 4 | pages = 603–617 | date = 2017 | pmid = 29103053 | doi = 10.3233/JPD-171209 | url = }}</ref><ref name="LiWuCui2023">{{cite journal | vauthors = Papakonstantinou T, Nikolakopoulou A, Higgins JP, Egger M, Salanti G | title = CINeMA: Software for semiautomated assessment of the confidence in the results of network meta-analysis | journal = Campbell Systematic Reviews | volume = 16 | issue = 1 | pages = e1080 | date = March 2020 | pmc = 10056828 | doi = 10.1002/14651858.CD014883 | pmid = 37131978 }}</ref><ref name="Lang2001">{{cite journal | vauthors = Lang AE | title = Acute orthostatic hypotension when starting dopamine agonist therapy in parkinson disease: the role of domperidone therapy | journal = Arch Neurol | volume = 58 | issue = 5 | pages = 835 | date = May 2001 | pmid = 11346387 | doi = 10.1001/archneur.58.5.835 | doi-broken-date = 11 November 2024 | url = }}</ref><ref name="LuchsingerGrilliVelasco1998">{{cite journal | vauthors = Luchsinger A, Grilli M, Velasco M | title = Metoclopramide and domperidone block the antihypertensive effect of bromocriptine in hypertensive patients | journal = Am J Ther | volume = 5 | issue = 2 | pages = 81–88 | date = March 1998 | pmid = 10099042 | doi = 10.1097/00045391-199803000-00005 | url = }}</ref><ref name="SchofferHendersonOMaley2007">{{cite journal | vauthors = Schoffer KL, Henderson RD, O'Maley K, O'Sullivan JD | title = Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson's disease | journal = Mov Disord | volume = 22 | issue = 11 | pages = 1543–1549 | date = August 2007 | pmid = 17557339 | doi = 10.1002/mds.21428 | url = }}</ref>

====Other gastrointestinal uses====
Domperidone may be used in [[functional dyspepsia]] in both adults and children.<ref>{{cite journal | vauthors = Xiao M, Qiu X, Yue D, Cai Y, Mo Q | title = Influence of hippophae rhamnoides on two appetite factors, gastric emptying and metabolic parameters, in children with functional dyspepsia | journal = Hellenic Journal of Nuclear Medicine | volume = 16 | issue = 1 | pages = 38–43 | year = 2013 | pmid = 23529392 | doi = <!-- not 10.1967/s002449910070 --> | url=https://www.nuclmed.gr/wp/wp-content/uploads/2017/03/42-4.pdf }}</ref><ref>{{cite journal | vauthors = Huang X, Lv B, Zhang S, Fan YH, Meng LN | title = Itopride therapy for functional dyspepsia: a meta-analysis | journal = World Journal of Gastroenterology | volume = 18 | issue = 48 | pages = 7371–7377 | date = December 2012 | pmid = 23326147 | pmc = 3544044 | doi = 10.3748/wjg.v18.i48.7371 | doi-access = free }}</ref> It has also been found effective in the treatment of [[gastroesophageal reflux disease|reflux]] in children.<ref>{{cite book| vauthors = Kapoor AK, Raju SM |year=2013|title=Illustrated Medical Pharmacology|chapter=7.2 Gastrointestinal Drugs|chapter-url=https://books.google.com/books?id=Le28AQAAQBAJ&pg=PA677|publisher=JP Medical Ltd|page=677|isbn=978-9350906552|access-date=31 October 2014}} (Google Books)</ref> However some specialists consider its risks prohibitory of the treatment of infantile reflux.<ref>{{Cite news|url=https://www.telegraph.co.uk/health/healthnews/11005559/Fear-that-reflux-treatment-for-babies-will-be-denied-under-new-Nice-guidance.html |title=Fear that reflux treatment for babies will be denied under new Nice guidance | vauthors = Smith R |date=1 August 2014 |publisher=[[The Daily Telegraph]] |access-date=31 October 2014 |archive-url=https://web.archive.org/web/20141005121124/http://www.telegraph.co.uk/health/healthnews/11005559/Fear-that-reflux-treatment-for-babies-will-be-denied-under-new-Nice-guidance.html |archive-date=5 October 2014 |url-status=dead  }}</ref>

===Available forms===
Domperidone is available for use by [[oral administration]] in the form of [[tablet (pharmacy)|tablet]]s, [[orally disintegrating tablet]]s (ODTs) and [[suspension (chemistry)|suspension]], and by [[rectal administration]] in the form of [[suppository|suppositories]].<ref name="ema" /><ref name="mhra"/> The oral tablets are available in the strength of 10{{nbsp}}mg.<ref name="mechanismforantiemetic"/> Domperidone has been studied for use by [[intramuscular injection]] and an [[intravenous injection|intravenous]] formulation was previously available, but the medication is now only available in forms for oral and rectal administration.<ref name="mechanismforantiemetic"/>

==Veterinary uses==
Domperidone is used as immunotherapy to treat [[leishmania]] in dogs.<ref>{{cite journal | vauthors = Travi BL, Miró G | title = Use of domperidone in canine visceral leishmaniasis: gaps in veterinary knowledge and epidemiological implications | journal = Memórias do Instituto Oswaldo Cruz | volume = 113 | issue = 11 | pages = e180301 | date = October 2018 | pmid = 30365645 | pmc = 6193371 | doi = 10.1590/0074-02760180301 }}</ref>

Domperidone also has an FDA-approved formulation for the prevention of fescue toxicosis in periparturient mares.<ref>{{Cite web |title=EQUIDONE® Gel (domperidone) |url=https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=e55d075e-2fe2-4405-b57a-59b85067e0c0 |access-date=2024-10-25 |website=dailymed.nlm.nih.gov}}</ref>

==Contraindications==
Domperidone is [[contraindication|contraindicated]] with [[QT-prolonging drug]]s like [[amiodarone]].<ref name="MIMS">Swannick G. (ed.) "MIMS Australia." December 2013</ref>

==Side effects==
Side effects associated with domperidone include [[dry mouth]], [[abdominal cramp]]s, [[diarrhea]], [[nausea]], [[rash]], [[pruritus|itching]], [[urticaria|hives]], and [[hyperprolactinemia]] (the symptoms of which may include [[mammoplasia|breast enlargement]], [[galactorrhea]], [[mastodynia|breast pain/tenderness]], [[gynecomastia]], [[hypogonadism]], and [[irregular menstruation|menstrual irregularities]]).<ref name="Henderson2003"/>

Due to the blockade of D<sub>2</sub> receptors in the [[central nervous system]], D<sub>2</sub> receptor antagonists like [[metoclopramide]] and [[antipsychotic]]s can also produce a variety of additional side effects including [[drowsiness]], [[akathisia]], [[psychomotor agitation|restlessness]], [[insomnia]], [[lassitude]], [[fatigue (medicine)|fatigue]], [[extrapyramidal symptom]]s, [[dystonia]], [[parkinsonism|Parkinsonian symptom]]s, [[tardive dyskinesia]], and [[depression (mood)|depression]].<ref name="mechanismforantiemetic"/><ref name="pmid10332535" /> However, this is not the case with domperidone, because, unlike other D<sub>2</sub> receptor antagonists, it minimally crosses the [[blood–brain barrier]], and for this reason, is rarely associated with such side effects.<ref name="mechanismforantiemetic"/><ref name="pmid10332535" /> However, domperidone theoretically might be able to produce some blockade of central D<sub>2</sub> receptors at higher doses, in turn producing side effects similar to those of centrally permeable D<sub>2</sub> receptor antagonists like antipsychotics.<ref name="pmid24660005">{{cite journal | vauthors = Ferrier J | title = Domperidone as an unintended antipsychotic | journal = Canadian Pharmacists Journal | volume = 147 | issue = 2 | pages = 76–77 | date = March 2014 | pmid = 24660005 | pmc = 3962062 | doi = 10.1177/1715163514521969 }}</ref>

===Elevated prolactin levels===
Due to D<sub>2</sub> receptor blockade, domperidone causes [[hyperprolactinemia]].<ref name="JoslinKahn2005">{{cite book| vauthors = Proctor EJ, Kahn CR |author2-link = C. Ronald Kahn |title=Joslin's Diabetes Mellitus: Edited by C. Ronald Kahn ... &#91;et Al.&#93;|url=https://books.google.com/books?id=ohgjG0qAvfgC&pg=PA1084|year=2005|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-2796-9|pages=1084–}}</ref> Hyperprolactinemia can suppress the secretion of [[gonadotropin-releasing hormone]] (GnRH) from the [[hypothalamus]], in turn suppressing the secretion of [[follicle-stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH) and resulting in [[hypogonadism]] and low levels of the [[sex hormone]]s [[estradiol]] and [[testosterone]].<ref name="Jr.2010">{{cite book| vauthors = Sabanegh Jr ES |title=Male Infertility: Problems and Solutions|url=https://books.google.com/books?id=YthJpK5clTMC&pg=PA83|date=20 October 2010|publisher=Springer Science & Business Media|isbn=978-1-60761-193-6|pages=83–}}</ref> Accordingly, 10 to 15% of females have been reported to experience [[mammoplasia]] (breast enlargement), [[mastodynia]] (breast pain/tenderness), [[galactorrhea]] (inappropriate or excessive milk production/secretion), and [[amenorrhea]] (cessation of [[menstrual cycle]]s) with domperidone therapy.<ref name="JoslinKahn2005" /> Males may experience low [[libido]], [[erectile dysfunction]], and impaired [[spermatogenesis]], as well as [[galactorrhea]] and [[gynecomastia]].<ref name="Jr.2010" /><ref name="BriggsFreeman2012">{{cite book| vauthors = Briggs GG, Freeman RK, Yaffe SJ |title=Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk|url=https://books.google.com/books?id=ScPvM03B3lUC&pg=PA442|date=28 March 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-5359-0|pages=442–}}</ref> D<sub>2</sub> receptor antagonists like [[antipsychotic]]s and domperidone may also increase the risk of [[prolactinoma]]s, but more research is needed to confirm this.<ref name="pmid20455888">{{cite journal | vauthors = Holt RI, Peveler RC | title = Antipsychotics and hyperprolactinaemia: mechanisms, consequences and management | journal = Clinical Endocrinology | volume = 74 | issue = 2 | pages = 141–147 | date = February 2011 | pmid = 20455888 | doi = 10.1111/j.1365-2265.2010.03814.x | s2cid = 21617834 }}</ref><ref name="pmid20592331">{{cite journal | vauthors = Bushe CJ, Bradley A, Pendlebury J | title = A review of hyperprolactinaemia and severe mental illness: are there implications for clinical biochemistry? | journal = Annals of Clinical Biochemistry | volume = 47 | issue = Pt 4 | pages = 292–300 | date = July 2010 | pmid = 20592331 | doi = 10.1258/acb.2010.010025 | s2cid = 21948581 }}</ref><ref name="pmid30531551">{{cite journal | vauthors = Lertxundi U, Erezuma I, Hernandez R, Medrano J, Garcia M, Aguirre C | title = Antipsychotics and pituitary tumors: an analysis of the European pharmacovigilance database (EudraVigilance) | journal = International Clinical Psychopharmacology | volume = 34 | issue = 2 | pages = 89–92 | date = March 2019 | pmid = 30531551 | doi = 10.1097/YIC.0000000000000247 | s2cid = 54476916 }}</ref><ref name="DurraniVasireddyArshad2023">{{cite journal | vauthors = Durrani US, Vasireddy S, Arshad MZ, Paracha A, Paracha MA, Waheed F, Abid A, Siddiqui Z, Thomure M | title = The Effect of Antipsychotics on Prolactinoma Growth: A Radiological and Serological Analysis | journal = Cureus | volume = 15 | issue = 11 | pages = e49342 | date = November 2023 | pmid = 38143631 | pmc = 10748855 | doi = 10.7759/cureus.49342 | doi-access = free | url = }}</ref>

===Rare reactions===

====Cardiac complications====
Domperidone use is associated with an increased risk of [[sudden cardiac death]] (by 70%)<ref name="pmid26649742">{{cite journal | vauthors = Leelakanok N, Holcombe A, Schweizer ML | title = Domperidone and Risk of Ventricular Arrhythmia and Cardiac Death: A Systematic Review and Meta-analysis | journal = Clinical Drug Investigation | volume = 36 | issue = 2 | pages = 97–107 | date = February 2016 | pmid = 26649742 | doi = 10.1007/s40261-015-0360-0 | s2cid = 25601738 }}</ref> most likely through its prolonging effect of the cardiac [[QT interval]] and [[ventricular arrhythmia]]s.<ref>{{cite journal | vauthors = van Noord C, Dieleman JP, van Herpen G, Verhamme K, Sturkenboom MC | title = Domperidone and ventricular arrhythmia or sudden cardiac death: a population-based case-control study in the Netherlands | journal = Drug Safety | volume = 33 | issue = 11 | pages = 1003–1014 | date = November 2010 | pmid = 20925438 | doi = 10.2165/11536840-000000000-00000 | s2cid = 21177240 }}</ref><ref>{{cite journal | vauthors = Johannes CB, Varas-Lorenzo C, McQuay LJ, Midkiff KD, Fife D | title = Risk of serious ventricular arrhythmia and sudden cardiac death in a cohort of users of domperidone: a nested case-control study | journal = Pharmacoepidemiology and Drug Safety | volume = 19 | issue = 9 | pages = 881–888 | date = September 2010 | pmid = 20652862 | doi = 10.1002/pds.2016 | s2cid = 20323199 | doi-access = free }}</ref> The cause is thought to be [[channel blocker|blockade]] of [[hERG]] [[voltage-gated potassium channel]]s.<ref name="pmid20394569">{{cite journal | vauthors = Rossi M, Giorgi G | title = Domperidone and long QT syndrome | journal = Current Drug Safety | volume = 5 | issue = 3 | pages = 257–262 | date = July 2010 | pmid = 20394569 | doi = 10.2174/157488610791698334 }}</ref><ref name="pmid24147629">{{cite journal | vauthors = Doggrell SA, Hancox JC | title = Cardiac safety concerns for domperidone, an antiemetic and prokinetic, and galactogogue medicine | journal = Expert Opinion on Drug Safety | volume = 13 | issue = 1 | pages = 131–138 | date = January 2014 | pmid = 24147629 | doi = 10.1517/14740338.2014.851193 | s2cid = 30668496 | url = https://eprints.qut.edu.au/65613/2/65613.pdf }}</ref> The risks are dose-dependent, and appear to be greatest with high/very high doses via intravenous administration and in the elderly, as well as with drugs that interact with domperidone and increase its circulating concentrations (namely [[CYP3A4]] inhibitors).<ref name="MarziWeitz2015">{{cite journal | vauthors = Marzi M, Weitz D, Avila A, Molina G, Caraballo L, Piskulic L | title = [Cardiac adverse effects of domperidone in adult patients: a systematic review] | journal = Revista Médica de Chile | volume = 143 | issue = 1 | pages = 14–21 | date = January 2015 | pmid = 25860264 | doi = 10.4067/S0034-98872015000100002 | doi-access = free | hdl = 2133/10526 | hdl-access = free }}</ref><ref name="pmid26117678">{{cite journal | vauthors = Buffery PJ, Strother RM | title = Domperidone safety: a mini-review of the science of QT prolongation and clinical implications of recent global regulatory recommendations | journal = The New Zealand Medical Journal | volume = 128 | issue = 1416 | pages = 66–74 | date = June 2015 | pmid = 26117678 }}</ref> Conflicting reports exist, however.<ref name="OrtizCooper2015">{{cite journal | vauthors = Ortiz A, Cooper CJ, Alvarez A, Gomez Y, Sarosiek I, McCallum RW | title = Cardiovascular safety profile and clinical experience with high-dose domperidone therapy for nausea and vomiting | journal = The American Journal of the Medical Sciences | volume = 349 | issue = 5 | pages = 421–424 | date = May 2015 | pmid = 25828198 | pmc = 4418779 | doi = 10.1097/MAJ.0000000000000439 }}</ref> In neonates and infants, QT prolongation is controversial and uncertain.<ref>{{cite journal | vauthors = Djeddi D, Kongolo G, Lefaix C, Mounard J, Léké A | title = Effect of domperidone on QT interval in neonates | journal = The Journal of Pediatrics | volume = 153 | issue = 5 | pages = 663–666 | date = November 2008 | pmid = 18589449 | doi = 10.1016/j.jpeds.2008.05.013 }}</ref><ref>{{cite journal | vauthors = Günlemez A, Babaoğlu A, Arisoy AE, Türker G, Gökalp AS | title = Effect of domperidone on the QTc interval in premature infants | journal = Journal of Perinatology | volume = 30 | issue = 1 | pages = 50–53 | date = January 2010 | pmid = 19626027 | pmc = 2834362 | doi = 10.1038/jp.2009.96 }}</ref>

UK drug regulatory authorities (MHRA) have issued the following restriction on domperidone in 2014 due to increased risk of adverse cardiac effects:<ref name="MHRA2014">{{Cite web|url=http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON418518|title = Domperidone: Risks of cardiac side effects}}</ref>

{{Blockquote|''Domperidone (Motilium) is associated with a small increased risk of serious cardiac side effects. Its use is now restricted to the relief of nausea and vomiting and the dosage and duration of use have been reduced. It should no longer be used for the treatment of bloating and heartburn. Domperidone is now contraindicated in those with underlying cardiac conditions and other risk factors. Patients with these conditions and patients receiving long-term treatment with domperidone should be reassessed at a routine appointment, in light of the new advice.''}}

However, a 2015 Australian review concluded the following:<ref name="pmid26117678" />

{{Blockquote|''Based on the results of the two TQT (the regulatory agency gold standard for assessment of QT prolongation) domperidone does not appear to be strongly associated with QT prolongation at oral doses of 20 mg QID in healthy volunteers. Further, there are limited case reports supporting an association with cardiac dysfunction, and the frequently cited case-control studies have significant flaws. While there remains an ill-defined risk at higher systemic concentrations, especially in patients with a higher baseline risk of QT prolongation, our review does not support the view that domperidone presents intolerable risk.''}}

====Possible central toxicity in infants====
In Britain, a legal case involved the death of two children of a mother whose three children had all had [[hypernatraemia]]. She was charged with poisoning the children with salt. One of the children, who was born at 28 weeks gestation with [[respiratory]] complications and had a [[fundoplication]] for [[gastroesophageal reflux]] and [[failure to thrive]] was prescribed domperidone. An [[advocate]] for the mother suggested the child may have had [[neuroleptic malignant syndrome]] as a side effect of domperidone due to the drug crossing the child's immature [[blood–brain barrier]].<ref>{{cite journal | vauthors = Coulthard MG, Haycock GB | title = Distinguishing between salt poisoning and hypernatraemic dehydration in children | journal = BMJ | volume = 326 | issue = 7381 | pages = 157–160 | date = January 2003 | pmid = 12531853 | pmc = 1128889 | doi = 10.1136/bmj.326.7381.157 }}</ref>

== Interactions ==

In healthy volunteers, the [[CYP3A4]] [[enzyme inhibitor|inhibitor]] [[ketoconazole]] increased the [[Cmax (pharmacology)|C<sub>max</sub>]] and [[Area under the curve (pharmacokinetics)|AUC]] concentrations of domperidone by 3- to 10-fold.<ref name="Aronson2009">{{cite book| vauthors = Aronson JK |title=Meyler's Side Effects of Antimicrobial Drugs|url=https://books.google.com/books?id=Zu2s5QBqiEkC&pg=PT2244|date=27 November 2009|publisher=Elsevier|isbn=978-0-08-093293-4|pages=2244–}}</ref> This was accompanied by a QT interval prolongation of about 10–20 milliseconds when domperidone 10&nbsp;mg four times daily and ketoconazole 200&nbsp;mg twice daily were administered, whereas domperidone by itself at the dosage assessed produced no such effect.<ref name="Aronson2009" /> As such, domperidone with ketoconazole or other CYP3A4 inhibitors is a potentially dangerous combination.<ref name="Aronson2009" />

==Pharmacology==

===Pharmacodynamics===
Domperidone is a [[peripherally selective drug|peripherally selective]] [[dopamine]] [[D2 receptor|D<sub>2</sub>]] and [[D3 receptor|D<sub>3</sub> receptor]] [[receptor antagonist|antagonist]].<ref name="pmid10332535" /> It has no clinically significant interaction with the [[D1 receptor|D<sub>1</sub> receptor]], unlike [[metoclopramide]].<ref name="pmid10332535" /> The medication provides relief from nausea by blocking D<sub>2</sub> receptors in the [[chemoreceptor trigger zone]] and from gastrointestinal symptoms by blocking D<sub>2</sub> receptors in the gut.<ref name="pmid25475074" /><ref name="mechanismforantiemetic"/> It blocks D<sub>2</sub> receptors in the [[lactotroph]]s of the [[anterior pituitary]] gland increasing release of [[prolactin]] which in turn increases [[lactation]].<ref name="pmid25475074" /><ref>Saeb-Parsy K. [https://books.google.com/books?id=F4-IdTewurIC "Instant pharmacology."] John Wiley & Sons, 1999 {{ISBN|0471976393}}, 9780471976394 p216.</ref><ref>{{cite journal | vauthors = Sakamoto Y, Kato S, Sekino Y, Sakai E, Uchiyama T, Iida H, Hosono K, Endo H, Fujita K, Koide T, Takahashi H, Yoneda M, Tokoro C, Goto A, Abe Y, Kobayashi N, Kubota K, Maeda S, Nakajima A, Inamori M | title = Effects of domperidone on gastric emptying: a crossover study using a continuous real-time 13C breath test (BreathID system) | journal = Hepato-Gastroenterology | volume = 58 | issue = 106 | pages = 637–641 | year = 2011 | pmid = 21661445 }}</ref> Domperidone may be more useful in some patients and cause harm in others by way of the [[genotype|genetics]] of the person, such as [[polymorphism (biology)|polymorphism]]s in the drug transporter [[gene]] ''ABCB1'' (which encodes [[P-glycoprotein]]), the [[voltage-gated potassium channel]] ''KCNH2'' gene ([[hERG|hERG/K<sub>v</sub>11.1]]), and the [[Alpha-1D adrenergic receptor|α<sub>1D</sub>-adrenergic receptor]] ''ADRA1D'' gene.<ref>{{cite journal | vauthors = Parkman HP, Jacobs MR, Mishra A, Hurdle JA, Sachdeva P, Gaughan JP, Krynetskiy E | title = Domperidone treatment for gastroparesis: demographic and pharmacogenetic characterization of clinical efficacy and side-effects | journal = Digestive Diseases and Sciences | volume = 56 | issue = 1 | pages = 115–124 | date = January 2011 | pmid = 21063774 | doi = 10.1007/s10620-010-1472-2 | s2cid = 39632855 }}</ref>

====Effects on prolactin levels====
A single 20&nbsp;mg oral dose of domperidone has been found to increase mean serum prolactin levels (measured 90 minutes post-administration) in non-lactating women from 8.1&nbsp;ng/mL to 110.9&nbsp;ng/mL (a 13.7-fold increase).<ref name="pmid10332535" /><ref name="pmid12192964">{{cite journal | vauthors = Gabay MP | title = Galactogogues: medications that induce lactation | journal = Journal of Human Lactation | volume = 18 | issue = 3 | pages = 274–279 | date = August 2002 | pmid = 12192964 | doi = 10.1177/089033440201800311 | s2cid = 29261467 }}</ref><ref name="pmid3882143">{{cite journal | vauthors = Hofmeyr GJ, Van Iddekinge B, Blott JA | title = Domperidone: secretion in breast milk and effect on puerperal prolactin levels | journal = British Journal of Obstetrics and Gynaecology | volume = 92 | issue = 2 | pages = 141–144 | date = February 1985 | pmid = 3882143 | doi = 10.1111/j.1471-0528.1985.tb01065.x | s2cid = 25489895 }}</ref><ref name="pmid7428183">{{cite journal | vauthors = Brouwers JR, Assies J, Wiersinga WM, Huizing G, Tytgat GN | title = Plasma prolactin levels after acute and subchronic oral administration of domperidone and of metoclopramide: a cross-over study in healthy volunteers | journal = Clinical Endocrinology | volume = 12 | issue = 5 | pages = 435–440 | date = May 1980 | pmid = 7428183 | doi = 10.1111/j.1365-2265.1980.tb02733.x | s2cid = 27266775 }}</ref> This was similar to the increase in prolactin levels produced by a single 20&nbsp;mg oral dose of metoclopramide (7.4&nbsp;ng/mL to 124.1&nbsp;ng/mL; 16.7-fold increase).<ref name="pmid3882143" /><ref name="pmid7428183" /> After two weeks of repeated administration (30&nbsp;mg/day in both cases), the increase in prolactin levels produced by domperidone was reduced (53.2&nbsp;ng/mL; 6.6-fold above baseline), but the increase in prolactin levels produced by metoclopramide, conversely, was heightened (179.6&nbsp;ng/mL; 24.3-fold above baseline).<ref name="pmid10332535" /><ref name="pmid7428183" /> This indicates that acute and continuous administration of both domperidone and metoclopramide is effective in increasing prolactin levels, but that there are different effects on the secretion of prolactin with repeated use.<ref name="pmid3882143" /><ref name="pmid7428183" /> The mechanism of the difference is unknown.<ref name="pmid7428183" /> The increase in prolactin levels observed with the two drugs was much greater in women than in men.<ref name="pmid3882143" /><ref name="pmid7428183" /> This appears to be due to the higher [[estrogen]] levels in women, as estrogen stimulates prolactin secretion from the [[pituitary gland]].<ref name="pmid7460861">{{cite journal | vauthors = Fujino T, Kato H, Yamashita S, Aramaki S, Morioka H, Koresawa M, Miyauchi F, Toyoshima H, Torigoe T | title = Effects of domperidone on serum prolactin levels in human beings | journal = Endocrinologia Japonica | volume = 27 | issue = 4 | pages = 521–525 | date = August 1980 | pmid = 7460861 | doi = 10.1507/endocrj1954.27.521 | doi-access = free }}</ref>

For comparison, normal prolactin levels in women are less than 20&nbsp;ng/mL, prolactin levels peak at 100 to 300&nbsp;ng/mL at [[parturition]] in [[pregnancy|pregnant]] women, and in lactating women, prolactin levels have been found to be 90&nbsp;ng/mL at 10 days postpartum and 44&nbsp;ng/mL at 180 days postpartum.<ref name="Riordan2005">{{cite book| vauthors = Riordan J |title=Breastfeeding and Human Lactation|url=https://books.google.com/books?id=aiVesab_2bwC&pg=PA76|date=January 2005|publisher=Jones & Bartlett Learning|isbn=978-0-7637-4585-1|pages=76–}}</ref><ref name="Becker2001">{{cite book| vauthors = Becker KL |title=Principles and Practice of Endocrinology and Metabolism|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA147|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=147–}}</ref>

===Pharmacokinetics===

====Absorption====
The [[absolute bioavailability]] of domperidone is low (13–17% or approximately 15%).<ref name="EMC-Domperidone" /><ref name="mechanismforantiemetic"/> This is due to extensive [[first-pass metabolism]] in the [[intestine]]s and [[liver]].<ref name="EMC-Domperidone" /> Conversely, its bioavailability is high via [[intramuscular injection]] (90%).<ref name="mechanismforantiemetic"/> The [[onset of action]] of domperidone taken orally is about 30 to 60&nbsp;minutes.<ref name="NHS-Domperidone" /><ref name="mechanismforantiemetic"/> Peak levels of domperidone following an oral dose occur after about 60&nbsp;minutes.<ref name="EMC-Domperidone">{{Cite web|url=https://www.medicines.org.uk/emc/product/556/smpc|title = Domperidone 10mg Tablets - Summary of Product Characteristics (SMPC) - (Emc)}}</ref> Domperidone exposure increases proportionally with doses in the 10 to 20&nbsp;mg dose range.<ref name="EMC-Domperidone" /> There is a 2- to 3-fold accumulation in levels of domperidone with frequent repeated oral administration of domperidone (four times per day (every 5&nbsp;hours) for 4&nbsp;days).<ref name="EMC-Domperidone" /> The oral [[bioavailability]] of domperidone is somewhat increased, and time to peak slightly increased when it is taken with food and bioavailability is decreased by prior concomitant administration of [[cimetidine]] and [[sodium bicarbonate]].<ref name="EMC-Domperidone" />

====Distribution====
The [[plasma protein binding]] of domperidone is 91 to 93%.<ref name="EMC-Domperidone" /> The [[tissue distribution]] of domperidone based on animal studies is wide, but concentrations are low in the brain.<ref name="EMC-Domperidone" /> The drug is a [[substrate (chemistry)#Bioavailability|substrate]] for the [[P-glycoprotein]] (ABCB1) transporter, and animal studies suggest that this is the reason for the low [[central nervous system]] penetration of domperidone.<ref name="BardalWaechter2011">{{cite book| vauthors = Bardal SK, Waechter JE, Martin DS |title=Applied Pharmacology|url=https://books.google.com/books?id=nYPy70d1E50C&pg=PA184|year=2011|publisher=Elsevier Health Sciences|isbn=978-1-4377-0310-8|pages=184–}}</ref> Small amounts of domperidone cross the [[placenta]] in animals.<ref name="EMC-Domperidone" />

====Metabolism====
Domperidone is extensively [[metabolism|metabolized]] in the [[liver]] and [[intestine]]s with oral administration.<ref name="EMC-Domperidone" /><ref name="SimardMichaud2008" /><ref name="pmid26059917" /> This occurs via [[hydroxylation]] and [[N-dealkylation]].<ref name="EMC-Domperidone" /> Domperidone is almost exclusively metabolized by [[CYP3A4]]/[[CYP3A5|5]], though minor contributions by [[CYP1A2]], [[CYP2D6]], and [[CYP2C8]] have been reported.<ref name="pmid26059917">{{cite journal | vauthors = Youssef AS, Parkman HP, Nagar S | title = Drug-drug interactions in pharmacologic management of gastroparesis | journal = Neurogastroenterology and Motility | volume = 27 | issue = 11 | pages = 1528–1541 | date = November 2015 | pmid = 26059917 | doi = 10.1111/nmo.12614 | s2cid = 34728070 }}</ref><ref name="SimardMichaud2008" /> CYP3A4 is the major enzyme involved in the N-dealkylation of domperidone, while CYP3A4, CYP1A2, and [[CYP2E1]] are involved in its aromatic hydroxylation.<ref name="EMC-Domperidone" /> All of the [[metabolite]]s of domperidone are inactive as D<sub>2</sub> receptor ligands.<ref name="mechanismforantiemetic"/><ref name="SimardMichaud2008" /> Overall and peak levels of domperidone are increased by about 2.9- and 1.5-fold in moderate [[hepatic impairment]], respectively.<ref name="EMC-Domperidone" />

====Elimination====
Domperidone is [[elimination (pharmacology)|eliminated]] 31% in urine and 66% in feces.<ref name="EMC-Domperidone" /> The proportion of domperidone excreted unchanged is small (10% in feces and 1% in urine).<ref name="EMC-Domperidone" /> The [[biological half-life|elimination half-life]] of domperidone is about 7 to 9&nbsp;hours in healthy individuals.<ref name="EMC-Domperidone" /><ref name="mechanismforantiemetic"/> However, the elimination half-life of domperidone can be prolonged to 20&nbsp;hours in people with severe [[renal dysfunction]].<ref name="EMC-Domperidone" /><ref name="mechanismforantiemetic"/>

==Chemistry==
Domperidone is a derivative of [[2-Benzimidazolinone|benzimidazolinone]]. It is structurally related to [[butyrophenone]] [[neuroleptic]]s like [[haloperidol]].<ref name="HospitalFormulary1991">{{cite book|title=Hospital Formulary|url=https://books.google.com/books?id=3oVMAQAAIAAJ|year=1991|publisher=HFM Publishing Corporation|page=171|quote=Domperidone, a benzimidazole derivative, is structurally related to the butyrophenone tranquilizers (eg, haloperidol (Haldol, Halperon]).}}</ref><ref name="BiggioCosta2013">{{cite book| vauthors = Biggio G, Costa E, Spano PF |title=Receptors as Supramolecular Entities: Proceedings of the Biannual Capo Boi Conference, Cagliari, Italy, 7-10 June 1981|url=https://books.google.com/books?id=8VAJAwAAQBAJ&pg=PA3|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4831-5550-0|pages=3–}}</ref>

==History==
Domperidone was synthesized at [[Janssen Pharmaceutica]] in 1974 following their research on [[Antipsychotic|antipsychotic drugs]].<ref name="dd">{{cite book| vauthors = Sneader W |date=2005|title=Drug discovery : a history|chapter=Plant Product Analogues and Compounds Derived from Them|location=Chichester|publisher=John Wiley & Sons Ltd|page=125|isbn=978-0-471-89979-2}}</ref><ref name="pmid18507654">{{cite journal | vauthors = Wan EW, Davey K, Page-Sharp M, Hartmann PE, Simmer K, Ilett KF | title = Dose-effect study of domperidone as a galactagogue in preterm mothers with insufficient milk supply, and its transfer into milk | journal = British Journal of Clinical Pharmacology | volume = 66 | issue = 2 | pages = 283–289 | date = August 2008 | pmid = 18507654 | pmc = 2492930 | doi = 10.1111/j.1365-2125.2008.03207.x }}</ref>  Janssen pharmacologists discovered that some antipsychotic drugs had a significant effect on [[dopamine receptor]]s in the [[Chemoreceptor trigger zone|central chemoreceptor trigger zone]] that regulated [[vomiting]], and started searching for a dopamine [[Receptor antagonist|antagonist]] that would not pass the [[blood–brain barrier]], thereby being free of the [[extrapyramidal symptoms|extrapyramidal side effects]] that were associated with drugs of this type.<ref name="dd" /> This led to the discovery of domperidone as a strong antiemetic with minimal central effects.<ref name="dd" /><ref>{{cite book | vauthors = Corsini GU | veditors = Ban TA, Healy D, Shorter E |title=The Triumph of Psychopharacology and the Story of CINP|publisher=CINP|year=2010|page=54|chapter=Apomorphine: from experimental tool to therapeutic aid|chapter-url=http://cinp.org/fileadmin/documents/history/books/VOL2_opt.pdf|isbn=978-9634081814 |archive-url=https://www.webcitation.org/6TlHgQUT7?url=http://cinp.org/fileadmin/documents/history/books/VOL2_opt.pdf|archive-date=1 November 2014}}</ref> Domperidone was [[patent]]ed in the United States in 1978, with the patent filed in 1976{{Citation needed|date=March 2022}}. In 1979, domperidone was first marketed, under the brand name Motilium, in Switzerland and West Germany.<ref name="WilliamAndrewPublishing2013">{{cite book|title=Pharmaceutical Manufacturing Encyclopedia, 3rd Edition (Vol. 1-4)|publisher=William Andrew Publishing|year=2013|page=138|chapter=Domperidone|chapter-url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1381|isbn=9780815518563|access-date=12 December 2014}}</ref> Domperidone was subsequently introduced in the forms of [[orally disintegrating tablet]]s (based on [[Zydis]] technology) in 1999.<ref>{{cite book| vauthors = Rathbone MJ, Hadgraft J, Roberts MS |date=2002|title=Modified-Release Drug Delivery Technology|chapter=The Zydis Oral Fast-Dissolving Dosage Form|chapter-url=https://books.google.com/books?id=mw9W82MLYZ8C&pg=PA200|publisher=CRC Press|page=[https://archive.org/details/modifiedreleased00mich/page/200 200]|isbn=9780824708696|access-date=31 October 2014|url-access=registration|url=https://archive.org/details/modifiedreleased00mich}}</ref>

In April 2014, the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) published an official press release suggesting restricting the use of domperidone-containing medicines. It also approved earlier published suggestions by [[European Medicines Agency|Pharmacovigilance Risk Assessment Committee (PRAC)]] to use domperidone only for treating [[nausea]] and [[vomiting]] and reduce maximum daily dosage to 10[[Orders of magnitude (mass)|mg]].<ref name="ema">{{Cite press release |url=https://www.ema.europa.eu/en/news/cmdh-confirms-recommendations-restricting-use-domperidone-containing-medicines |title=CMDh confirms recommendations on restricting use of domperidone-containing medicines |date=25 April 2014 |publisher=[[European Medicines Agency]] |access-date=31 October 2014 |archive-url=https://web.archive.org/web/20160130200137/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fnews_and_events%2Fnews%2F2014%2F04%2Fnews_detail_002083.jsp |archive-date=30 January 2016 |url-status=live }}</ref>

==Society and culture==

===Generic names===
''Domperidone'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA466|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=466–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA366|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=366–}}</ref><ref name="Drugs.com">{{Cite web | url=https://www.drugs.com/international/domperidone.html |title = Domperidone | work = Drugs.com }}</ref>

===Regulatory approval===
It was reported in 2007 that domperidone is available in 58 countries,<ref name="mechanismforantiemetic"/> but the uses or ''indications'' of domperidone vary between nations. In Italy it is used in the treatment of [[gastroesophageal reflux disease]] and in Canada, the drug is indicated in upper gastrointestinal motility disorders and to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents.<ref>[http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/bulletin/carn-bcei_v17n1-eng.pdf "Domperidone - heart rate and rhythm disorders."] Canadian adverse reactions newsletter. Government of Canada. January 2007 17(1)</ref> In the United Kingdom, domperidone is only indicated for the treatment of nausea and vomiting and the treatment duration is usually limited to 1 week.

In the United States, domperidone is not a legally marketed human drug and it is not approved for sale in the United States.<ref name="FDA 20231212" /> In June 2004, the [[Food and Drug Administration]] (FDA) issued a warning that distributing any domperidone-containing products is illegal.<ref name="FDA 20231212" />

It is available [[over-the-counter]] to treat [[gastroesophageal reflux disease]] and functional dyspepsia in many countries, such as Ireland, the Netherlands, Italy, South Africa, Mexico, India, Chile, and China.<ref name="FaisVermiglio2015">{{cite journal | vauthors = Fais P, Vermiglio E, Laposata C, Lockwood R, Gottardo R, De Leo D | title = A case of sudden cardiac death following Domperidone self-medication | journal = Forensic Science International | volume = 254 | pages = e1–e3 | date = September 2015 | pmid = 26119456 | doi = 10.1016/j.forsciint.2015.06.004 }}</ref>

Domperidone is not approved for use in the United States.<ref name="FDA 20231212" /> There is an exception for use in people with treatment-refractory gastrointestinal symptoms under an FDA [[Investigational New Drug]] application.<ref name="mechanismforantiemetic"/><ref name="FDA 20231212" />

===Formulations===
{| class="wikitable collapsible collapsed" style="font-size:small; width:100%;"
! colspan="4" | Formulations
|-
! Nation
! Manufacturer
! Brand
! Formulations
|-
| Australia || Janssen–Cilag || Motilium || 10&nbsp;mg scored tablets<ref name="MIMS"/>
|-
| Belgium and the Netherlands || - || Motilium || From 2013 only by prescription in Belgium.<ref>{{cite web|url=https://www.standaard.be/cnt/dmf20130507_00571810 |title=Motilium nog enkel op voorschrift |work=De Standaard |publisher=standaard.be |date=7 May 2013 |access-date=3 October 2013}}</ref>
|-
| Bangladesh || Square || Motigut || 10&nbsp;mg scored tablets
|-
| Bangladesh || Orion Pharma || Cosy || 10&nbsp;mg scored tablets
|-
| Bangladesh || Astra Pharma || Domperon || 10&nbsp;mg scored tablets
|-
| Bangladesh || - || Ridon || -
|-
| Canada || - || Motilium (1985–2002) || Generic brands available
|-
| France || Janssen || Motilium || 10&nbsp;mg tablets only with prescription generic domperidone available
|-
| Greece || Johnson & Johnson Hellas || Cilroton || 10&nbsp;mg scored tablets
|-
| India || Salius Pharma || Escacid DXR || pantoprazole 40&nbsp;mg and domperidone SR 30&nbsp;mg
|-
| India || FDC Pharmaceuticals || Pepcia-D || Rabeprazole 20&nbsp;mg and Domperidone SR 30&nbsp;mg
|-
| India || Rhubarb pharmaceuticals || - || domperidone 5, 10 and 20&nbsp;mg tablets.
|-
| India || [[Ipca Laboratories]], Mumbai || Domperi suspension || domperidone 1&nbsp;mg/ml, 30 ml suspension.<ref>{{cite web|url=http://www.ipcalabs.com/ |title=ipcalabs.com |publisher=ipcalabs.com |access-date=30 June 2013}}</ref>
|-
| India || Torrent pharmaceuticals || Domstal || -<ref>{{cite web|url=http://www.torrentpharma.com/ |title=torrentpharma.com |publisher=torrentpharma.com |access-date=30 June 2013}}</ref>
|-
| India || Ozone pharmaceuticals and chemicals || Pantazone-D ||10&nbsp;mg domperidone and 40&nbsp;mg pantoprazole
|-
| India || Chimak Health Care || Pancert D ||10&nbsp;mg Domperidone and 40&nbsp;mg pantoprazole
|-
| India || Draavin Pharma || Draaci-XD ||Pantaprazole 40&nbsp;mg and Domperione 30&nbsp;mg
|-
| Indonesia || Gratia Husada Farma (HUFA) || Hufadon || 10&nbsp;mg caplet
|-
| Indonesia || Mutiara Mukti Farma || Omedom || 10&nbsp;mg tablet
|-
| Indonesia || IFARS || Vesperum || 10&nbsp;mg tablet
|-
| Indonesia || Dexa Medica || Vometa FT || 10&nbsp;mg tablet
|-
| Indonesia || Sanbe || Vosedon || domperidone 5&nbsp;mg/ml, 60 ml suspension  
|-
| Iran || Abidi Pharmaceutical Co. || MOTiDON || 10&nbsp;mg tablet
|-
| Ireland || McNeil Healthcare || Motilium || 10&nbsp;mg [[Orally disintegrating tablet|orally disintegrating tablet (ODT)]]
|-
| Italy || - || Peridon || domperidone 10&nbsp;mg tablets; 30 ml suspension
|-
| Lithuania || Johnson & Johnson || Motilium || -
|-
| Pakistan || Barrett Hodgson Pakistan || Domel ||
|-
| Pakistan || Johnson & Johnson Pakistan || Motilium-v || domperidone 10&nbsp;mg tablets; 30 ml suspension
|-
| Pakistan || ATCO Laboratories Limited || Vomilux || domperidone 10&nbsp;mg tablets
|-
| Pakistan || Aspin Pharma (Pvt) Limited || Motilium || domperidone 10&nbsp;mg tablets
|-
| Philippines || Health Saver Pharma || Abdopen || -
|-
| Philippines || United Laboratories, Inc. || GI Norm || -
|-
| Philippines || Glorious Dexa Mandaya || Vometa || domperidone 1&nbsp;mg/mL oral suspension, 1&nbsp;mg/mL oral drops
|-
| Philippines || Glorious Dexa Mandaya || Vometa FT || domperidone 10&nbsp;mg fast-melting tablets
|-
| Portugal || Medinfar || Cinet || domperidone 1&nbsp;mg/ml oral suspension (200 ml)
|-
| Russia || Janssen Pharmaceutica || Motilium || domperidone 10&nbsp;mg film-coated tablets & ODT; 1&nbsp;mg/ml suspension (100 ml)
|-
| - || OBL Pharm || Passagix || domperidone 10&nbsp;mg film-coated tablets & chewable tablets
|-
| - || [[Dr. Reddy's|Dr. Reddy's Laboratories]] || Omez D || domperidone/omeprazole (10&nbsp;mg/10&nbsp;mg)
|-
| Saudi Arabia || JamJoom Pharmaceuticals || Dompy || Domperidone 10&nbsp;mg tablets
|-
| Spain
| Laboratorios Dr. Esteve, SA
| Motilium
| domperidone 1&nbsp;mg/ml oral suspension (200 ml)
|-
| Sweden || Ebb medical || Domperidon Ebb (2013) || domperidone 10&nbsp;mg ODT and peppermint
|-
| Syrian Arab Republic || Oubari Pharma || Motin || Domperidone 10&nbsp;mg Tablets and 1&nbsp;mg/ml Oral Suspension
|-
| Taiwan || - || Dotitone || -
|-
| Thailand || - || Motilium M || -
|-
| Turkey || Saba || Motinorm || -
|-
| - || [[GlaxoSmithKline]] || Motinorm || -
|}

==Research==
Domperidone has been studied as a potential [[hormonal contraceptive]] to prevent [[pregnancy]] in women.<ref name="HofmeyrVan Iddekinge2009">{{cite journal| vauthors = Hofmeyr GJ, Van Iddekinge B, Van Der Walt LA |title=Effect of domperidone-induced hyperprolactinaemia on the menstrual cycle; a placebo-controlled study|journal=Journal of Obstetrics and Gynaecology|volume=5|issue=4|year=1985|pages=263–264|issn=0144-3615|doi=10.3109/01443618509067772}}</ref>

== References ==
{{Reflist}}

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[[Category:Antiemetics]]
[[Category:Antihypotensive agents]]<!-- Treatment of dopamine receptor agonist-induced orthostatic hypotension -->
[[Category:Belgian inventions]]
[[Category:Chloroarenes]]
[[Category:Dopamine antagonists]]
[[Category:HERG blocker]]
[[Category:Janssen Pharmaceutica]]
[[Category:Motility stimulants]]
[[Category:Peripherally selective drugs]]
[[Category:Piperidines]]
[[Category:Potassium channel blockers]]
[[Category:Prolactin releasers]]
[[Category:Ureas]]