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Domperidone

Clinical data
Trade names	Motilium
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	Not classified (US)
Routes of administration	Oral, intravenous, rectal
ATC code	A03FA03 (WHO)
Legal status
Legal status	Not 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
Pharmacokinetic data
Bioavailability	High
Protein binding	91–93%
Metabolism	Hepatic and intestinal (first-pass)
Elimination half-life	7 hours
Excretion	Breast milk, renal
Identifiers
IUPAC name 5-chloro-1-(1-imidazol-1-yl)propyl]piperidin-4-yl)-1H-benzoimidazol-2(3H)-one
CAS Number	57808-66-9
PubChem CID	3151
DrugBank	DB01184
ChemSpider	3039
UNII	5587267Z69
KEGG	D01745
ChEBI	CHEBI:31515
ChEMBL	ChEMBL219916
CompTox Dashboard (EPA)	DTXSID1045116
ECHA InfoCard	100.055.408
Chemical and physical data
Formula	C22H24ClN5O2
Molar mass	425.911 g/mol g·mol
3D model (JSmol)	Interactive image
SMILES Clc1cc2c(cc1)N(C(=O)N2)C5CCN(CCCN4c3ccccc3NC4=O)CC5
InChI InChI=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) Key:FGXWKSZFVQUSTL-UHFFFAOYSA-N
(verify)

Domperidone (trade names Motilium, Motillium, Motinorm and Costi) is an antidopaminergic drug, developed by Janssen Pharmaceutica, and used orally, rectally or intravenously, generally to suppress nausea and vomiting, or as a prokinetic agent. It has also been used to stimulate lactation.

Uses

Gastrointestinal problems

There is some evidence that domperidone has antiemetic activity. Domperidone is used, together with metoclopramide, cyclizine, and 5HT₃ receptor antagonists (such as granisetron) in the treatment of nausea and vomiting.

Domperidone is a first choice antiemetic in some countries. 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 can be used in patients with Parkinson's disease because, unlike metoclopramide, domperidone does not cross the blood-brain barrier.

Domperidone has also been found effective in the treatment of gastroparesis, 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".

Lactation

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, it is sometimes self-prescribed from original research or prescribed "off-label" for this use in countries around the world.

Controversy

Janssen Pharmaceutical has brought domperidone before the FDA several times in the last two decades, with the most recent effort in the 1990s. Numerous U.S. clinical drug trials have demonstrated its safety and efficacy in dealing with gastroparesis symptoms, but the FDA turned down Janssen's application for domperidone, even though the FDA's division of gastrointestinal drugs had approved domperidone.

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 was 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. A recent paper suggests there may be increased risk of seizures to neonates of mothers taking oral domperidone.

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 the drug is safe in the doses given for this purpose since the morbidity in question was limited to intravaneous use. The American Academy of Pediatrics considers domperidone "usually compatible with breastfeeding".

There is a new controversy in Britain regarding lethal levels of sodium found in children who are administered this drug. It is now subject to a medical review following a number of criminal trials where parents were charged with child abuse by salt poisoning based on hypernatremia in the affected children. Recent studies also cite increased QT intervals in neonates taking Domperidone.

Pharmacology

Domperidone blocks the action of dopamine. 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 - among others - regulates nausea and vomiting (area postrema on the floor of the fourth ventricle and rhomboid fossa).

Brand

Brand-name Motilium was available in Canada from 1985-2002, but generic versions of the drug are still available.

See also

• itopride
• metoclopramide
• benzamide
• cisapride

References

1. Domperidone MedSafe NZ Government
2. Swann IL, Thompson EN, Qureshi K (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
3. Shindler JS, Finnerty GT, Towlson K, Dolan AL, Davies CL, Parkes JD (1984). "Domperidone and levodopa in Parkinson's disease". British journal of clinical pharmacology. 18 (6): 959–62. PMC 1463696. PMID 6529536. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
6. http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/bulletin/carn-bcei_v17n1-eng.pdf
7. Domperidone for lactating women, Canadian Medical Association Journal, Orlando P. da Silva and David C. Knoppert. 2004 Sep 28;171(7):725-6.
8. ^ FDA Warns Against Women Using Unapproved Drug, Domperidone, to Increase Milk Production U.S. Food and Drug Administration
9. Letter to Consumer Safety Office, FDA Gastroparesis and Dysmotilities Association
10. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDAWarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/ucm054623.pdf
11. Journal of Pediatrics 2008
12. Official Statements From Prominent Physicians breastfeedingonline.com
14. Maternal Medication Usually Compatible With Breastfeeding American Academy of Pediatrics
15. Current news coverage of latest trial The Scotsman
16. 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
17. "PDSP Ki Database".
18. http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/bulletin/carn-bcei_v17n1-eng.pdf

External links

• GPDA letter to the FDA about domperidone for gastroparesis
• U.S. National Library of Medicine: Drug Information Portal - Domperidone

• Antiemetics
• Motility stimulants
• Piperidines
• Benzimidazoles
• Ureas
• Organochlorides
• Janssen Pharmaceutica