|Systematic (IUPAC) name|
|Oral, intravenous, rectal|
|Metabolism||Hepatic and intestinal (first-pass)|
|Biological half-life||7.5 hours|
|Excretion||Breast milk, renal|
|CAS Registry Number|
|ATC code||A03 QP51|
|Molecular mass||425.911 g/mol|
|(what is this?)|
Domperidone (INN, USAN, BAN, JAN) (trade names Motilium, Motillium, Motinorm Costi, Nomit, Brulium Molax) is a medication developed by Janssen Pharmaceutica that acts as a peripherally selective antagonist of the dopamine D2 and D3 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 and hormone) 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 Synthesis
- 9 See also
- 10 References
- 11 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 increases lower esophageal sphincter pressure by blocking dopamine receptors in the gastric antrum and the duodenum. It blocks dopamine receptors in the anterior 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 is not currently a legally marketed human drug and it is not approved for sale in the U.S. On June 7, 2004, FDA issued a public warning that distributing any domperidone-containing products is illegal. "How to Obtain" http://www.fda.gov. Page Last Updated: 02/10/2015 Retrieved 2015-08-04. 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.
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 worsen 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 especially when given intravenously, in elderly people and in high doses (> 30 mg 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 neuroleptic malignant syndrome as a side effect of domperidone due to the drug crossing the child's immature blood brain barrier.
UK drug regulatory authorities (MHRA) have issued the following restriction on Domperidone due to increased risk of adverse cardiac effects. "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"
Other side effects
Due to D2 receptor blockade, domperidone causes hyperprolactinemia. Hyperprolactinemia can suppress the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus, in turn suppressing the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and resulting in hypogonadism (low sex hormone (e.g., testosterone, estradiol) levels). As such, male patients may experience low libido, erectile dysfunction, and impaired spermatogenesis. Also in accordance with hyperprolactinemia, 10–15% of female patients have been reported to experience mammoplasia (breast enlargement), mastodynia (breast pain/tenderness), galactorrhea (inappropriate or excessive milk production/secretion), and amenorrhea (cessation of menstrual cycles) with domperidone treatment. Gynecomastia has been reported in males treated with domperidone, and galactorrhea could occur in males as well.
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)
- Cardiac disease
Those taking QT-prolonging medicines or CYP3A4 inhibitors at the same time as domperidone.
1974 - Domperidone synthesized at Janssen Pharmaceutica following the research on antipsychotic drugs. Janssen pharmacologists discovered that some of antipsychotic drugs had a significant effect on dopamine receptors in the central chemoreceptor trigger zone that regulated vomiting and started searching for a dopamine antagonist that would not pass the blood–brain barrier, thereby being free of the extrapyramidal side effects that were associated with drugs of this type. This led to the discovery of domperidone as a strong anti-emetic with minimal central effects.
1978 - On January 3, 1978 Domperidone was patented in the USA under patent US4066772 A. The application has been filed on May 17, 1976. Jan Vandenberk, Ludo E. J. Kennis, Marcel J. M. C. Van der Aa and others has been cited as the inventors.
Janssen Pharmaceutical has brought domperidone before the United States Federal Drug Administration (FDA) several times, including in the 1990s.
2014 - In April 2014 Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) published official press-release suggesting to restrict the use of domperidone-containing medicines. It also approved earlier published suggestions by Pharmacovigilance Risk Assessment Committee (PRAC) to use domperidone only for curing nausea and vomiting and reduce maximum daily dosage to 10 mg.
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.|
|Bangladesh||Square||Motigut||10 mg scored tablets|
|Canada||-||Motilium (1985–2002)||Generic brands available|
|India||Salius Pharma||Escacid DXR||pantoprazole 40 mg and domperidone SR 30 mg|
|India||Medley pharmaceuticals||Dompan||pantoprazole 40 mg and domperidone 10 mg|
|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|
|India||Chimak Health Care||Pancert D||10 mg Domperidone and 40 mg pantoprazole|
|Iran||Abidi Pharmaceutical Co.||MOTiDON||10 mg tablet|
|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||-|
|Philippines||United Laboratories, Inc.||GI Norm||-|
|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)|
|Sweden||Ebb medical||Domperidon Ebb (2013)||domperidone 10 mg ODT and peppermint|
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