|Systematic (IUPAC) name|
|Pregnancy cat.||Not classified (US)|
|Legal status||Not approved for use or sale: US; prescription medicine (POM): India, Australia, Canada, Israel, Belgium; Over the Counter (OTC): UK (Pharmacy only), Egypt, Ireland, Italy, Japan, Netherlands, South Africa, Switzerland, China, Russia, Slovakia, Thailand, Malta, South Korea, and Romania|
|Routes||Oral, intravenous, rectal|
|Metabolism||Hepatic and intestinal (first-pass)|
|Excretion||Breast milk, renal|
|ATC code||A03 QP51|
|Mol. mass||425.911 g/mol|
|(what is this?)|
Domperidone (trade names Motilium, Motillium, Motinorm Costi, Nomit and Molax) is a medication developed by Janssen Pharmaceutica that is a peripheral, specific blocker of dopamine receptors. It is administered orally, rectally, or intravenously. Domperidone is given in order to relieve nausea and vomiting; to increase the transit of food through the stomach (as a prokinetic agent through increase in gastrointestinal peristalsis); and to increase lactation (breast milk production) by release of prolactin. It is also used in the scientific study of the way dopamine (an important neurotransmitter) acts in the body.
- 1 Mechanism of Action
- 2 Uses
- 3 Adverse effects
- 4 Interactions
- 5 Contraindications
- 6 History
- 7 Brand names and formulations by nation
- 8 See also
- 9 References
- 10 External links
Mechanism of Action
Domperidone is a peripheral dopamine (D2) and (D3) receptor antagonist. It provides relief from nausea by blocking receptors at the chemo-receptor trigger zone (a location in the nervous system that registers nausea) at the floor of the fourth ventricle (a location near the brain). It increases motility in the upper gastrointestinal tract to a moderate degree and lowers esophageal sphincter pressure by blocking dopamine receptors in the gastric antrum and the duodenum. It blocks dopamine receptors in the posterior pituitary gland increasing release of prolactin which in turn increases lactation. Domperidone may be more useful in some patients and cause harm in others by way of the genetic characteristic of the person, such as polymorphisms in the drug transporter gene ABCB1, the potassium channel KCNH2 gene, and α1D--adrenoceptor ADRA1D gene.
The uses or indications of domperidone vary between nations. For instance, 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. In the United States domperidone's use is not approved, though patients with various gastrointestinal conditions may qualify for access through the Expanded Access to Investigational Drugs program.
Nausea and vomiting
Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there is no mechanical gastric outlet obstruction. Its cause is most commonly idiopathic, a diabetic 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.
However, increased rate of gastric emptying induced by drugs like domperidone does not always correlate (equate) well with relief of symptoms.
Parkinson's disease is a chronic neurological condition where a decrease in dopamine in the brain leads to rigidity (stiffness of movement), tremor and other symptoms and signs. Poor gastrointestinal function, nausea and vomiting is a major problem for people with Parkinson's disease because most medications used to treat Parkinson's disease are given by mouth. These medications, such as levodopa can cause nausea as a side effect. Furthermore, anti-nausea drugs, such as metoclopramide, which do cross the blood brain barrier may worsen the extra-pyramidal symptoms of Parkinson's disease.
Domperidone can be used to relieve gastrointestinal symptoms in Parkinson's disease, because, even though it blocks dopamine receptors (which would be expected to worse Parkinson's disease), it does not cross the blood brain barrier (the barrier between the blood circulation of the brain and the rest of the body). In addition to this, domperidone may enhance the bioavailability (effect) of levodopa (one of the main treatments in Parkinson's disease.)
Although these features make domperidone a useful drug in Parkinson's disease, caution is needed due to the cardiotoxic side effects of domperidone when given intravenously, in elderly people and in high doses (> 30mg per day). A clinical sign of domperidone's potential toxicity to the heart is the prolongation (lengthening) of the QT interval (a segment of the heart's electrical pattern).
The hormone prolactin stimulates lactation (production of breast milk). Dopamine, released by the hypothalamus stops the release of prolactin from the pituitary gland. Domperidone, by acting as an anti-dopaminergic agent, results in increased prolactin secretion, and thus promotes lactation (that is, it is a galactogogue). In some nations, including Australia, domperidone is used off label, based on uncertain and anecdotal evidence of its usefulness, as a therapy for mothers who are having difficulty breastfeeding. In the United States, domperidone is not approved for this or any other use. A study called the EMPOWER trial has been designed to assess the effectiveness and safety of domperidone in assisting mothers of preterm babies to supply breast milk for their infants.
Penetration of immature blood brain barrier
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 suffered neurolept malignant syndrome as a side effect of domperidone due to the drug crossing the child's immature blood brain barrier.
Erythromycin and other macrolide antibiotics inhibit the metabolism of domperidone (in-vitro) thus increasing the concentration of domperidone and potential side effects of the drug. This is of concern as both drugs may be used to treat gastroparesis.
- Prolactin secreting pituitary tumor.
- Triazole antifungal medications such as ketoconazole, itraconazole, fluconazole.
- Macrolide antibiotics such as erythromycin and clarithromycin.
- Potent CYP3A4 inhibitors.
- Mechanical bowel disorders such as bowel obstruction, gastrointestinal haemorrhage or bowel perforation
- Moderate hepatic impairment (liver disease).
Janssen Pharmaceutical has brought domperidone before the United States Federal Drug Administration (FDA) several times, including in the 1990s.
Brand names and formulations by nation
|Australia||Janssen–Cilag||Motilium||10 mg scored tablets|
|Belgium and the Netherlands||-||Motilium||From 2013 only by prescription in Belgium.|
|Canada||-||Motilium (1985–2002)||Generic brands available|
|India||Salius Pharma||Escacid DXR||pantoprazole 40 mg and domperidone SR 30mg|
|India||Medley pharmaceuticals||Dompan||pantoprazole 40 mg and domperidone 10mg|
|India||Rhubarb pharmaceuticals||-||domperidone 5, 10 and 20 mg tablets.|
|India||Ipca Laboratories, Mumbai||Domperi suspension||domperidone 1 mg/ml, 30 ml suspension.|
|India||Torrent pharmaceuticals||Domstal||- |
|India||Ozone pharmaceuticals and chemicals||Pantazone-D||10 mg domperidone and 40 mg pantoprazole|
|Ireland||McNeil Healthcare||Motilium||10 mg orally disintegrating tablet (ODT)|
|Pakistan||Johnson & Johnson Pakistan||Motilium-v||domperidone 10 mg tablets; 30 ml suspension|
|Philippines||Health Saver Pharma||Abdopen||-|
|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)|
|Sweden||Ebb medical||Domperidon Ebb (2013)||domperidone 10 mg ODT and peppermint|
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