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| Clinical data | |
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| Trade names | Motilium, others |
| Other names | R-33812; R33812; KW-5338; KW5338; NSC-299589; NSC299589 |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| Pregnancy category | |
| Routes of administration | By mouth,rectal[2] |
| Drug class | D2 receptor antagonist;Prolactin releaser |
| ATC code | |
| Legal status | |
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| Pharmacokinetic data | |
| Bioavailability | Oral: 13–17%[2][6] Intramuscular: 90%[2] |
| Protein binding | ~92%[2] |
| Metabolism | Hepatic (CYP3A4/5) andintestinal (first-pass)[2][7] |
| Metabolites | All inactive[2][7] |
| Onset of action | 30–60 minutes[8] |
| Eliminationhalf-life | 7–9 hours[9][2][6] |
| Excretion | Feces: 66%[2] Urine: 32%[2] Breast milk: small quantities[2] |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.055.408 |
| Chemical and physical data | |
| Formula | C22H24ClN5O2 |
| Molar mass | 425.92 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 242.5 °C (468.5 °F) |
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Domperidone, sold under the brand nameMotilium among others, is adopamine antagonistmedication which is used to treatnausea andvomiting and certaingastrointestinal problems likegastroparesis (delayedgastric emptying). It raises the level ofprolactin in the human body.[2][10] It may be takenby mouth orrectally.[2][11][12]
Side effects may includeheadache, anxiety,dry mouth,abdominal cramps,diarrhea, andelevated prolactin levels.[13][2][10][14] Secondary to increased prolactin levels,breast changes,milk outflow,menstrual irregularities, andhypogonadism can occur.[2][10][14] Domperidone may also causeQT prolongation and has rarely been associated with seriouscardiac complications such assudden cardiac death.[15][16][17][18] However, the risks are small and occur more with high doses.[18][19] Domperidone acts as aperipherally selectiveantagonist of thedopamineD2 andD3 receptors.[2][10] Due to its low entry into thebrain, the side effects of domperidone are different from those of other dopamine receptor antagonists likemetoclopramide and it produces little in the way ofcentral nervous system adverse effects.[2][10] However, domperidone can nonetheless increase prolactin levels as thepituitary gland is outside of theblood–brain barrier.[20]
Domperidone was discovered in 1974 and was introduced for medical use in 1979.[21][22][23] It was developed byJanssen Pharmaceutica.[21][22] Domperidone is availableover-the-counter in many countries, for instance in Europe and elsewhere throughout the world.[24][2] It is not approved for use in the United States.[25][26][2] However, it is available in the United States for people with severe and treatment-refractory gastrointestinal motility problems under anexpanded access individual-patientinvestigational new drug application.[25] Ananalogue of domperidone calleddeudomperidone is under development for potential use in the United States and other countries.[27][28][29]
There is some evidence that domperidone hasantiemetic activity.[2] It is recommended by the Canadian Headache Society for treatment of nausea associated with acutemigraine.[30]
Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there isno mechanicalgastric outlet obstruction. Its cause is most commonlyidiopathic, adiabetic complication or a result of abdominal surgery. The condition causes nausea, vomiting,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 increasinggastrointestinalperistalsis and hence to treat gastroparesis.[2][10] It may be useful in idiopathic and diabetic gastroparesis.[31][32] However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate well with relief of symptoms.[33]
Domperidone is usedoff-label in some countries to stimulatelactation 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.[25][34] Domperidone acts as a peripheraldopamine antagonist and is hypothesized to stimulateprolactin secretion, with a 2003 study supporting that hypothesis.[26]
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.[35] Domperidone has no officially established dosage for increasing milk supply, but most published studies have used 10 mg three times daily for 4 to 10 days (30 mg per day).[36]
The USFood and Drug Administration (FDA) has expressed concerns about serious adverse side effects and concerns about its effectiveness.[34] 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.[34]
A review byHealth 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 mg per day.[37] 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.[38]
Parkinson's disease is adegenerative neurological condition where a decrease indopamine in thebrain leads torigidity (stiffness of movement),tremor, and other symptoms and signs. Poorgastrointestinal function,nausea, andvomiting are major problems for people with Parkinson's disease because most medications used to treat Parkinson's disease are givenby mouth. Thesemedications, such aslevodopa, can also cause nausea as aside effect. Furthermore,anti-nausea drugs, such asmetoclopramide, which do cross theblood–brain barrier, may worsen theextrapyramidal symptoms of Parkinson's disease. Domperidone can be used to relieve nausea and gastrointestinal symptoms in Parkinson's disease; it blocks peripheral D2 receptors but minimally crosses the blood-brain barrier in normal doses, so has no effect on the extrapyramidal symptoms of the disease.[39][40][41] In addition, domperidone may be useful in the treatment oforthostatic hypotension caused bydopaminergic therapy in people with Parkinson's disease.[42][43][44][45][46]
Domperidone may be used infunctional dyspepsia in both adults and children.[47][48] It has also been found effective in the treatment ofreflux in children.[49] However some specialists consider its risks prohibitory of the treatment of infantile reflux.[50]
Domperidone is available for use byoral administration in the form oftablets,orally disintegrating tablets (ODTs) andsuspension, and byrectal administration in the form ofsuppositories.[11][12] The oral tablets are available in the strength of 10 mg.[2] Domperidone has been studied for use byintramuscular injection and anintravenous formulation was previously available, but the medication is now only available in forms for oral and rectal administration.[2]
Domperidone is used as immunotherapy to treatleishmania in dogs.[51]
Domperidone also has an FDA-approved formulation for the prevention of fescue toxicosis in periparturient mares.[52]
Domperidone iscontraindicated withQT-prolonging drugs likeamiodarone.[53]
Side effects associated with domperidone includedry mouth,abdominal cramps,diarrhea,nausea,rash,itching,hives, andhyperprolactinemia (the symptoms of which may includebreast enlargement,galactorrhea,breast pain/tenderness,gynecomastia,hypogonadism, andmenstrual irregularities).[14]
Due to the blockade of D2 receptors in thecentral nervous system, D2 receptor antagonists likemetoclopramide andantipsychotics can also produce a variety of additional side effects includingdrowsiness,akathisia,restlessness,insomnia,lassitude,fatigue,extrapyramidal symptoms,dystonia,Parkinsonian symptoms,tardive dyskinesia, anddepression.[2][10] However, this is not the case with domperidone, because, unlike other D2 receptor antagonists, it minimally crosses theblood–brain barrier, and for this reason, is rarely associated with such side effects.[2][10] However, domperidone theoretically might be able to produce some blockade of central D2 receptors at higher doses, in turn producing side effects similar to those of centrally permeable D2 receptor antagonists like antipsychotics.[54]
Due to D2 receptor blockade, domperidone causeshyperprolactinemia.[55] Hyperprolactinemia can suppress the secretion ofgonadotropin-releasing hormone (GnRH) from thehypothalamus, in turn suppressing the secretion offollicle-stimulating hormone (FSH) andluteinizing hormone (LH) and resulting inhypogonadism and low levels of thesex hormonesestradiol andtestosterone.[56] Accordingly, 10 to 15% of females have been reported to experiencemammoplasia (breast enlargement),mastodynia (breast pain/tenderness),galactorrhea (inappropriate or excessive milk production/secretion), andamenorrhea (cessation ofmenstrual cycles) with domperidone therapy.[55] Males may experience lowlibido,erectile dysfunction, and impairedspermatogenesis, as well asgalactorrhea andgynecomastia.[56][57] D2 receptor antagonists likeantipsychotics and domperidone may also increase the risk ofprolactinomas, but more research is needed to confirm this.[58][59][60][61]
Domperidone use is associated with an increased risk ofsudden cardiac death (by 70%)[15] most likely through its prolonging effect of the cardiacQT interval andventricular arrhythmias.[62][63] The cause is thought to beblockade ofhERGvoltage-gated potassium channels.[16][17] 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 (namelyCYP3A4 inhibitors).[19][18] Conflicting reports exist, however.[64] In neonates and infants, QT prolongation is controversial and uncertain.[65][66]
UK drug regulatory authorities (MHRA) have issued the following restriction on domperidone in 2014 due to increased risk of adverse cardiac effects:[67]
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:[18]
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.
In Britain, a legal case involved the death of two children of a mother whose three children had all hadhypernatraemia. She was charged with poisoning the children with salt. One of the children, who was born at 28 weeks gestation withrespiratory complications and had afundoplication forgastroesophageal reflux andfailure to thrive was prescribed domperidone. Anadvocate for the mother suggested the child may have hadneuroleptic malignant syndrome as a side effect of domperidone due to the drug crossing the child's immatureblood–brain barrier.[68]
In healthy volunteers, theCYP3A4inhibitorketoconazole increased theCmax andAUC concentrations of domperidone by 3- to 10-fold.[69] This was accompanied by a QT interval prolongation of about 10–20 milliseconds when domperidone 10 mg four times daily and ketoconazole 200 mg twice daily were administered, whereas domperidone by itself at the dosage assessed produced no such effect.[69] As such, domperidone with ketoconazole or other CYP3A4 inhibitors is a potentially dangerous combination.[69]
Domperidone is aperipherally selectivedopamineD2 andD3 receptorantagonist.[10] It has no clinically significant interaction with theD1 receptor, unlikemetoclopramide.[10] The medication provides relief from nausea by blocking D2 receptors in thechemoreceptor trigger zone and from gastrointestinal symptoms by blocking D2 receptors in the gut.[20][2] It blocks D2 receptors in thelactotrophs of theanterior pituitary gland increasing release ofprolactin which in turn increaseslactation.[20][70][71] Domperidone may be more useful in some patients and cause harm in others by way of thegenetics of the person, such aspolymorphisms in the drug transportergeneABCB1 (which encodesP-glycoprotein), thevoltage-gated potassium channelKCNH2 gene (hERG/Kv11.1), and theα1D-adrenergic receptorADRA1D gene.[72]
A single 20 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 ng/mL to 110.9 ng/mL (a 13.7-fold increase).[10][73][74][75] This was similar to the increase in prolactin levels produced by a single 20 mg oral dose of metoclopramide (7.4 ng/mL to 124.1 ng/mL; 16.7-fold increase).[74][75] After two weeks of repeated administration (30 mg/day in both cases), the increase in prolactin levels produced by domperidone was reduced (53.2 ng/mL; 6.6-fold above baseline), but the increase in prolactin levels produced by metoclopramide, conversely, was heightened (179.6 ng/mL; 24.3-fold above baseline).[10][75] 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.[74][75] The mechanism of the difference is unknown.[75] The increase in prolactin levels observed with the two drugs was much greater in women than in men.[74][75] This appears to be due to the higherestrogen levels in women, as estrogen stimulates prolactin secretion from thepituitary gland.[76]
For comparison, normal prolactin levels in women are less than 20 ng/mL, prolactin levels peak at 100 to 300 ng/mL atparturition inpregnant women, and in lactating women, prolactin levels have been found to be 90 ng/mL at 10 days postpartum and 44 ng/mL at 180 days postpartum.[77][78]
Theabsolute bioavailability of domperidone is low (13–17% or approximately 15%).[9][2] This is due to extensivefirst-pass metabolism in theintestines andliver.[9] Conversely, its bioavailability is high viaintramuscular injection (90%).[2] Theonset of action of domperidone taken orally is about 30 to 60 minutes.[8][2] Peak levels of domperidone following an oral dose occur after about 60 minutes.[9] Domperidone exposure increases proportionally with doses in the 10 to 20 mg dose range.[9] 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 hours) for 4 days).[9] The oralbioavailability 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 ofcimetidine andsodium bicarbonate.[9]
Theplasma protein binding of domperidone is 91 to 93%.[9] Thetissue distribution of domperidone based on animal studies is wide, but concentrations are low in the brain.[9] The drug is asubstrate for theP-glycoprotein (ABCB1) transporter, and animal studies suggest that this is the reason for the lowcentral nervous system penetration of domperidone.[79] Small amounts of domperidone cross theplacenta in animals.[9]
Domperidone is extensivelymetabolized in theliver andintestines with oral administration.[9][7][80] This occurs viahydroxylation andN-dealkylation.[9] Domperidone is almost exclusively metabolized byCYP3A4/5, though minor contributions byCYP1A2,CYP2D6, andCYP2C8 have been reported.[80][7] CYP3A4 is the major enzyme involved in the N-dealkylation of domperidone, while CYP3A4, CYP1A2, andCYP2E1 are involved in its aromatic hydroxylation.[9] All of themetabolites of domperidone are inactive as D2 receptor ligands.[2][7] Overall and peak levels of domperidone are increased by about 2.9- and 1.5-fold in moderatehepatic impairment, respectively.[9]
Domperidone iseliminated 31% in urine and 66% in feces.[9] The proportion of domperidone excreted unchanged is small (10% in feces and 1% in urine).[9] Theelimination half-life of domperidone is about 7 to 9 hours in healthy individuals.[9][2] However, the elimination half-life of domperidone can be prolonged to 20 hours in people with severerenal dysfunction.[9][2]
Domperidone is a derivative ofbenzimidazolinone. It is structurally related tobutyrophenoneneuroleptics likehaloperidol.[81][82]
Domperidone was synthesized atJanssen Pharmaceutica in 1974 following their research onantipsychotic drugs.[22][21] Janssen pharmacologists discovered that some antipsychotic drugs had a significant effect ondopamine receptors in thecentral chemoreceptor trigger zone that regulatedvomiting, and started searching for a dopamineantagonist that would not pass theblood–brain barrier, thereby being free of theextrapyramidal side effects that were associated with drugs of this type.[22] This led to the discovery of domperidone as a strong antiemetic with minimal central effects.[22][83] Domperidone waspatented in the United States in 1978, with the patent filed in 1976[citation needed]. In 1979, domperidone was first marketed, under the brand name Motilium, in Switzerland and West Germany.[23] Domperidone was subsequently introduced in the forms oforally disintegrating tablets (based onZydis technology) in 1999.[84]
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 byPharmacovigilance Risk Assessment Committee (PRAC) to use domperidone only for treatingnausea andvomiting and reduce maximum daily dosage to 10mg.[11]
Domperidone is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name,BANTooltip British Approved Name, andJANTooltip Japanese Accepted Name.[85][86][87]
It was reported in 2007 that domperidone is available in 58 countries,[2] but the uses orindications of domperidone vary between nations. In Italy it is used in the treatment ofgastroesophageal 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.[88] 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 there.[25] (There is an exception for use in people with treatment-refractory gastrointestinal symptoms under an FDAInvestigational New Drug application.[2][25]) In June 2004, theFood and Drug Administration (FDA) issued a warning that distributing any domperidone-containing products is illegal.[25]
It is availableover-the-counter to treatgastroesophageal reflux disease and functional dyspepsia in many countries, such as Ireland, the Netherlands, Italy, South Africa, Mexico, India, Chile, and China.[24]
| Formulations | |||
|---|---|---|---|
| Nation | Manufacturer | Brand | Formulations |
| Australia | Janssen–Cilag | Motilium | 10 mg scored tablets[53] |
| Belgium and the Netherlands | - | Motilium | From 2013 only by prescription in Belgium.[89] |
| Bangladesh | Square | Motigut | 10 mg scored tablets |
| Bangladesh | Orion Pharma | Cosy | 10 mg scored tablets |
| Bangladesh | Astra Pharma | Domperon | 10 mg scored tablets |
| Bangladesh | - | Ridon | - |
| Canada | - | Motilium (1985–2002) | Generic brands available |
| France | Janssen | Motilium | 10 mg tablets only with prescription generic domperidone available |
| Greece | Johnson & Johnson Hellas | Cilroton | 10 mg scored tablets |
| India | Salius Pharma | Escacid DXR | pantoprazole 40 mg and domperidone SR 30 mg |
| India | FDC Pharmaceuticals | Pepcia-D | Rabeprazole 20 mg and Domperidone SR 30 mg |
| India | Rhubarb pharmaceuticals | - | domperidone 5, 10 and 20 mg tablets. |
| India | Ipca Laboratories, Mumbai | Domperi suspension | domperidone 1 mg/ml, 30 ml suspension.[90] |
| India | Torrent pharmaceuticals | Domstal | -[91] |
| India | Ozone pharmaceuticals and chemicals | Pantazone-D | 10 mg domperidone and 40 mg pantoprazole |
| India | Chimak Health Care | Pancert D | 10 mg Domperidone and 40 mg pantoprazole |
| India | Draavin Pharma | Draaci-XD | Pantaprazole 40 mg and Domperione 30 mg |
| Indonesia | Gratia Husada Farma (HUFA) | Hufadon | 10 mg caplet |
| Indonesia | Mutiara Mukti Farma | Omedom | 10 mg tablet |
| Indonesia | IFARS | Vesperum | 10 mg tablet |
| Indonesia | Dexa Medica | Vometa FT | 10 mg tablet |
| Indonesia | Sanbe | Vosedon | domperidone 5 mg/ml, 60 ml suspension |
| Iran | Abidi Pharmaceutical Co. | MOTiDON | 10 mg tablet |
| Ireland | McNeil Healthcare | Motilium | 10 mgorally disintegrating tablet (ODT) |
| Italy | - | Peridon | domperidone 10 mg tablets; 30 ml suspension |
| Lithuania | Johnson & Johnson | Motilium | - |
| Pakistan | Barrett Hodgson Pakistan | Domel | |
| Pakistan | Johnson & Johnson Pakistan | Motilium-v | domperidone 10 mg tablets; 30 ml suspension |
| Pakistan | ATCO Laboratories Limited | Vomilux | domperidone 10 mg tablets |
| Pakistan | Aspin Pharma (Pvt) Limited | Motilium | domperidone 10 mg tablets |
| Philippines | Health Saver Pharma | Abdopen | - |
| Philippines | United Laboratories, Inc. | GI Norm | - |
| Philippines | Glorious Dexa Mandaya | Vometa | domperidone 1 mg/mL oral suspension, 1 mg/mL oral drops |
| Philippines | Glorious Dexa Mandaya | Vometa FT | domperidone 10 mg fast-melting tablets |
| Portugal | Medinfar | Cinet | domperidone 1 mg/ml oral suspension (200 ml) |
| Russia | Janssen Pharmaceutica | Motilium | domperidone 10 mg film-coated tablets & ODT; 1 mg/ml suspension (100 ml) |
| - | OBL Pharm | Passagix | domperidone 10 mg film-coated tablets & chewable tablets |
| - | Dr. Reddy's Laboratories | Omez D | domperidone/omeprazole (10 mg/10 mg) |
| Saudi Arabia | JamJoom Pharmaceuticals | Dompy | Domperidone 10 mg tablets |
| Spain | Laboratorios Dr. Esteve, SA | Motilium | domperidone 1 mg/ml oral suspension (200 ml) |
| Sweden | Ebb medical | Domperidon Ebb (2013) | domperidone 10 mg ODT and peppermint |
| Syrian Arab Republic | Oubari Pharma | Motin | Domperidone 10 mg Tablets and 1 mg/ml Oral Suspension |
| Taiwan | - | Dotitone | - |
| Thailand | - | Motilium M | - |
| Turkey | Saba | Motinorm | - |
| - | GlaxoSmithKline | Motinorm | - |
Domperidone has been studied as a potentialhormonal contraceptive to preventpregnancy in women.[92]
This article incorporates text from this source, which is in thepublic domain.
{{cite journal}}: CS1 maint: DOI inactive as of July 2025 (link)Domperidone, a benzimidazole derivative, is structurally related to the butyrophenone tranquilizers (eg, haloperidol (Haldol, Halperon]).
