Domperidone: Wikis

  
  

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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
Identifiers
CAS number 57808-66-9
ATC code A03FA03
PubChem 3151
DrugBank APRD00418
ChemSpider 3039
Chemical data
Formula C22H24ClN5O2 
Mol. mass 425.911 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability High
Protein binding 91–93%
Metabolism Hepatic and intestinal (first-pass)
Half life 7 hours
Excretion Breast milk, renal
Therapeutic considerations
Pregnancy cat. Not classified (US)
Legal status Not approved for use or sale: US; prescription medicine: India, Australia, Canada, Israel; Over the Counter (OTC): UK, Belgium, Egypt, Ireland, Italy, Japan, Netherlands, South Africa, Switzerland, China, Russia, Slovakia, Malta, South Korea, and Romania[1]
Routes Oral, intravenous, rectal
 Yes check.svgY(what is this?)  (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. It has also been used to stimulate lactation.

Contents

Uses

Gastrointestinal problems

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.

Domperidone is a first choice antiemetic in most 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 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).

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,[6] it is sometimes self-prescribed from original research or prescribed "off-label" for this use in countries around the world.[7]

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.[8]

In June 2004, the United States' main regulation agency, 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 with the drug include cardiac arrest and arrhythmia, complications with other medications, as well as complications with improper intravenous use[7]. A recent paper suggests there may be increased risk of seizures to neonates of mothers taking oral domperidone[9].

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 but have no evidential data or studies to base their claim.[10] The American Academy of Pediatrics considers domperidone "usually compatible with breastfeeding".[11]

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.[12] Recent studies also cite increased QT intervals in neonates taking Domperidone. [13].

Pharmacology

Domperidone blocks the action of dopamine. It has strong affinities for the D2 and D3 dopamine receptors [14], 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).

See also

Brand

Many brand names and combinations of the drug exist. The combination of domperidone 10mg/20mg and pantoprazole 40mg is marketed as Dompan by Medley Pharmaceuticals. Domperidone 5mg/10mg/20mg tablets and 30mg 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 India for Paediatric purpose Domperidone is available as Domperi Suspension(Domperidone 1 mg/ml, 30 ml Suspension;Ipca Laboratories Ltd, Bombay)[1]and Domstal(Torrent Pharmaceuticals Ltd.)[2]Rhubarb Pharmaceuticals Pvt. Ltd.

References

  1. ^ Domperidone MedSafe NZ Government
  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. 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. 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. ^ Domperidone for lactating women, Canadian Medical Association Journal, Orlando P. da Silva and David C. Knoppert. 2004 Sep 28;171(7):725-6.
  7. ^ a b FDA Warns Against Women Using Unapproved Drug, Domperidone, to Increase Milk Production U.S. Food and Drug Administration
  8. ^ Letter to Consumer Safety Office, FDA Gastroparesis and Dysmotilities Association
  9. ^ Journal of Pediatrics 2008
  10. ^ Official Statements From Prominent Physicians breastfeedingonline.com
  11. ^ Maternal Medication Usually Compatible With Breastfeeding American Academy of Pediatrics
  12. ^ Current news coverage of latest trial The Scotsman
  13. ^ 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. PMID 18589449. 
  14. ^ "PDSP Ki Database". http://pdsp.med.unc.edu/pdsp.php. 

External links








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