Domperidone

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Domperidone
Systematic (IUPAC) name
5-chloro-1-(1-[3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl]piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one
Clinical data
Trade namesMotilium
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy cat.Not classified (US)
Legal statusNot approved for use or sale: US; prescription medicine (POM): India, Australia, Canada, Israel; Over the Counter (OTC): UK (Pharmacy only), Belgium, Egypt, Ireland, Italy, Japan, Netherlands, South Africa, Switzerland, China, Russia, Slovakia, Thailand, Malta, South Korea, and Romania[1]
RoutesOral, intravenous, rectal
Pharmacokinetic data
BioavailabilityHigh
Protein binding91–93%
MetabolismHepatic and intestinal (first-pass)
Half-life7 hours
ExcretionBreast milk, renal
Identifiers
CAS number57808-66-9 YesY
ATC codeA03FA03 QP51AX24
PubChemCID 3151
IUPHAR ligand965
DrugBankDB01184
ChemSpider3039 YesY
UNII5587267Z69 YesY
KEGGD01745 YesY
ChEBICHEBI:31515 YesY
ChEMBLCHEMBL219916 YesY
Chemical data
FormulaC22H24ClN5O2 
Mol. mass425.911 g/mol
 YesY (what is this?)  (verify)
 
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Domperidone
Systematic (IUPAC) name
5-chloro-1-(1-[3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl]piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one
Clinical data
Trade namesMotilium
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy cat.Not classified (US)
Legal statusNot approved for use or sale: US; prescription medicine (POM): India, Australia, Canada, Israel; Over the Counter (OTC): UK (Pharmacy only), Belgium, Egypt, Ireland, Italy, Japan, Netherlands, South Africa, Switzerland, China, Russia, Slovakia, Thailand, Malta, South Korea, and Romania[1]
RoutesOral, intravenous, rectal
Pharmacokinetic data
BioavailabilityHigh
Protein binding91–93%
MetabolismHepatic and intestinal (first-pass)
Half-life7 hours
ExcretionBreast milk, renal
Identifiers
CAS number57808-66-9 YesY
ATC codeA03FA03 QP51AX24
PubChemCID 3151
IUPHAR ligand965
DrugBankDB01184
ChemSpider3039 YesY
UNII5587267Z69 YesY
KEGGD01745 YesY
ChEBICHEBI:31515 YesY
ChEMBLCHEMBL219916 YesY
Chemical data
FormulaC22H24ClN5O2 
Mol. mass425.911 g/mol
 YesY (what is this?)  (verify)

Domperidone (trade names Motilium, Motillium, Motinorm Costi and Nomit) is an antidopaminergic drug, developed by Janssen Pharmaceutica, and used orally, rectally, or intravenously, in general to suppress nausea and vomiting, as a prokinetic agent and for promoting lactation. It is a specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.

Uses[edit]

Gastrointestinal problems[edit]

There is some evidence that domperidone has antiemetic activity.[2] Domperidone is used, together with metoclopramide, cyclizine, and 5HT3 receptor antagonists (such as granisetron) in the treatment of nausea and vomiting. In Italy, it is also used for gastroesophageal reflux disease (GERD), as well as for hiatal hernia.

Domperidone is a first-choice antiemetic in some countries.[citation needed] However, it is not approved for prescription in the US. Although it has never been officially approved for use in the United States, domperidone is sometimes purchased from pharmacies in other countries for this purpose. It may be obtained through some compounding pharmacies in the US with a doctor's prescription.

It can be used in patients with Parkinson's disease[3] because, unlike metoclopramide,[4] domperidone does not cross the blood–brain barrier.

Domperidone has also been found effective in the treatment of gastroparesis,[5] a stomach motility condition, and for paediatric gastroesophageal reflux (infant vomiting).

In Canada, the drug is indicated "for the symptomatic management of upper gastrointestinal motility disorders associated with chronic and subacute gastritis and diabetic gastroparesis." The drug may also be used "to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents".[6]

Lactation[edit]

The hormone prolactin stimulates lactation in humans, and its release is inhibited by the dopamine secreted by the hypothalamus. Domperidone, by acting as an anti-dopaminergic, results in increased prolactin secretion, and thus promotes lactation.

Since, according to the U.S. Food and Drug Administration (FDA), domperidone is not approved for enhanced lactation in any country,[7] it is sometimes self-prescribed from original research or prescribed "off-label" for this use in countries around the world.[8]

Controversies[edit]

Janssen Pharmaceutical has brought domperidone before the FDA several times in the last two decades, with the most recent effort in the 1990s. In June 2004, the FDA issued a letter warning women not to take domperidone, citing unknown risks to parents and infants, and warned pharmacies that domestic sale is illegal, and that import shipments from other countries would be searched and seized. Domperidone is excreted in breast milk, and no studies on its effects on breastfeeding infants have been reported in the literature.

Individual incidents of problems in patients receiving an intravenous form of domperidone include cardiac arrest and arrhythmia, complications with other medications, as well as complications with improper intravenous use. This intravenous form has since been withdrawn from marketing in several countries.[8][9] A recent paper suggests that there may be increased risk of seizures to neonates of mothers taking oral domperidone.[10]

Some doctors and pharmacists do not fully accept the FDA's reasoning and still favor domperidone's use in increasing milk supply. Such doctors and pharmacists claim that the drug is safe in the doses given for this purpose[11] since the morbidity in question was limited to intravenous use.[12] The American Academy of Pediatrics considers domperidone "usually compatible with breastfeeding".[13]

There is a new controversy in Britain regarding lethal levels of sodium found in children administered this drug. It is now subject to a medical review following a number of criminal trials wherein parents were charged with child abuse by salt poisoning based on hypernatremia in the affected children.[14] Recent studies also cite increased QT intervals in neonates taking Domperidone.[15] A 2013 Belgian study warned about a risk of sudden cardiac death associated with domperidone, concluding that "[b]ecause domperidone has placebo-like benefits but is associated with increased SCD and a narrow safety margin, it should not be used in medicine."[16]

The Australian Therapeutic Goods Administration (TGA) has warned that (epidemiological) studies have suggested that the risk of sudden cardiac death and/or serious ventricular arrhythmias may be higher in patients using daily doses greater than 30 mg and in patients older than 60 years of age.[17]

The European Medicines Agency is reviewing the benefit-risk balance of medicines containing domperidone since March 7, 2013.

Mechanism of Action[edit]

Domperidone acts as a gastrointestinal emptying (delayed) adjunct and peristaltic stimulant. The gastroprokinetic properties of domperidone are related to its peripheral dopamine receptor-blocking properties. Domperidone facilitates gastric emptying and decreases small bowel transit time by increasing esophageal and gastric peristalsis and by lowering esophageal sphincter pressure. The antiemetic properties of domperidone are related to its dopamine receptor-blocking activity at both the chemoreceptor trigger zone and at the gastric level. It has strong affinities for the D2 and D3 dopamine receptors, which are found in the chemoreceptor trigger zone, located just outside the blood brain barrier, which regulates nausea and vomiting.

Brand[edit]

Many brand names and combinations of the drug exist. In India the brand name Escacid 40 & Escacid DXR of Salius Pharma contains Pantoprazole 40 mg and Pantoprazole 40 mg+ Domperidone 30 mg SR, respectively. The combination of domperidone 10 mg/20 mg and pantoprazole 40 mg is marketed as Dompan by Medley Pharmaceuticals. Domperidone 5 mg/10 mg/20 mg tablets and 30 mg oral suspension is marketed in North India by Rhubarb Pharmaceuticals. Domperidone is sold as Motinorm by GlaxoSmithKline, and as Motis by Saba in Turkey. In Italy, it is available with the brand name Peridon. In India for Paediatric purpose Domperidone is available as Domperi Suspension (Domperidone 1 mg/ml, 30 ml Suspension; Ipca Laboratories Ltd, Mumbai)[18] and Domstal (Torrent Pharmaceuticals Ltd.)[19] Rhubarb Pharmaceuticals Pvt. Ltd.

In Pakistan, it is marketed as 'Motilium' in 10 mg tablets/30 ml Suspension, manufactured by Johnson & Johnson Pakistan (Pvt) Ltd. It is also marketed in Ireland under the name 'Motilium' in 10 mg orodispersible tablets and manufactured by McNeil Healthcare (Ireland) Ltd.

In Belgium and The Netherlands Domperidone is also marketed as Motilium. The medicine was available without prescription in pharmacies. In March 2013, the Federal Agency for Medicines and Health Products of Belgium raised questions about the safety of the drug, mainly because it increases the risk of heart failure. As of the end of 2013, Motilium will only be available in pharmacies with a prescription.[20] An alternative, prescription-free drug with (mainly) the same effects is available under the brand name Primperan, produced by Sanofi-Aventis.

The combination of Domperidone 10 mg and Pantoprazole 40 mg [PANTAZONE-D] is Mfg. and supplied by Ozone pharmaceuticals and chemicals, Gujarat, India. Philippines brand 'Abdopen' manufacturer 'Health Saver Pharma Inc.'

Brand-name Motilium was available in Canada from 1985-2002, but generic versions of the drug are still available.[6] It is sold as Ridon in Bangladesh, Dotitone in Taiwan and as Motilium-M in Thailand.

See also[edit]

References[edit]

  1. ^ "Domperidone". Retrieved 2013-06-30. 
  2. ^ Swann IL, Thompson EN, Qureshi K (November 1979). "Domperidone or metoclopramide in preventing chemotherapeutically induced nausea and vomiting". British Medical Journal 2 (6199): 1188. doi:10.1136/bmj.2.6199.1188. PMC 1597274. PMID 519355. 
  3. ^ Shindler JS, Finnerty GT, Towlson K, Dolan AL, Davies CL, Parkes JD (December 1984). "Domperidone and levodopa in Parkinson's disease". British Journal of Clinical Pharmacology 18 (6): 959–62. PMC 1463696. PMID 6529536. 
  4. ^ Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
  5. ^ Silvers D, Kipnes M, Broadstone V, et al. (1998). "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". Clinical therapeutics 20 (3): 438–53. doi:10.1016/S0149-2918(98)80054-4. PMID 9663360. 
  6. ^ a b http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/bulletin/carn-bcei_v17n1-eng.pdf
  7. ^ Orlando P. da Silva*, David C. Knoppert†. "''Domperidone for lactating women'', Canadian Medical Association Journal, Orlando P. da Silva and David C. Knoppert. 2004 Sep 28;171(7):725-6". Cmaj.ca. Retrieved 2013-06-30. 
  8. ^ a b "FDA Warns Against Women Using Unapproved Drug, Domperidone, to Increase Milk Production". U.S. Food and Drug Administration. 
  9. ^ http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDAWarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/ucm054623.pdf
  10. ^ USA (2013-03-25). "Journal of Pediatrics 2008". Ncbi.nlm.nih.gov. Retrieved 2013-06-30. 
  11. ^ "Official Statements From Prominent Physicians". breastfeedingonline.com. 
  12. ^ "Breastfeeding Online". Breastfeeding Online. Retrieved 2013-06-30. 
  13. ^ "Maternal Medication Usually Compatible With Breastfeeding". American Academy of Pediatrics. 
  14. ^ "Current news coverage of latest trial". The Scotsman. 
  15. ^ Djeddi D, Kongolo G, Lefaix C, Mounard J, Léké A. (2008). "Effect of domperidone on QT interval in neonates.". Journal of Pediatrics 153 (5): 596–598. doi:10.1016/j.jpeds.2008.05.013. PMID 18589449. 
  16. ^ Hondeghem, L. M. (2013). "Domperidone". Journal of Cardiovascular Pharmacology 61 (3): 218–225. doi:10.1097/FJC.0b013e31827afd0d. PMID 23188128.  edit
  17. ^ "Volume 35 Number 6". Australian Prescriber. 2012-12-06. Retrieved 2013-06-30. 
  18. ^ "ipcalabs.com". ipcalabs.com. Retrieved 2013-06-30. 
  19. ^ "torrentpharma.com". torrentpharma.com. Retrieved 2013-06-30. 
  20. ^ "De Standaard: "Motilium from now on only with prescription"". standaard.be. 2013-05-07. Retrieved 2013-10-03. 

External links[edit]