Domperidone, sold under the brand name Motilium among others, is a dopamine antagonist medication which is used to treat nausea and vomiting and certain gastrointestinal problems like gastroparesis (delayed gastric emptying).
It raises the level of prolactin in the human body and is used off label to induce and promote breast milk production.
[2][11][12] Side effects may include headache, anxiety, dry mouth, abdominal cramps, diarrhea, and elevated prolactin levels.
[13][2][10][14] Secondary to increased prolactin levels, breast changes, milk outflow, menstrual irregularities, and hypogonadism can occur.
[25][26][2] However, it is available in the United States for people with severe and treatment-refractory gastrointestinal motility problems under an expanded access individual-patient investigational new drug application.
[30] Gastroparesis is a medical condition characterised by delayed emptying of the stomach when there is no mechanical gastric outlet obstruction.
[25][34] Domperidone acts as a peripheral dopamine antagonist and is hypothesized to stimulate prolactin secretion, with a 2003 study supporting that hypothesis.
The analysis also indicated that domperidone was well tolerated with no significant difference in maternal adverse events compared to placebo.
Additionally, discontinuation or tapering of domperidone has been linked to severe neuropsychiatric adverse events such as agitation, anxiety, and suicidal ideation.
[38] Parkinson's disease is a degenerative neurological condition where a decrease in dopamine in the brain leads to rigidity (stiffness of movement), tremor, and other symptoms and signs.
[39][40][41] In addition, domperidone may be useful in the treatment of orthostatic hypotension caused by dopaminergic therapy in people with Parkinson's disease.
[53] Side effects associated with domperidone include dry mouth, abdominal cramps, diarrhea, nausea, rash, itching, hives, and hyperprolactinemia (the symptoms of which may include breast enlargement, galactorrhea, breast pain/tenderness, gynecomastia, hypogonadism, and menstrual irregularities).
[14] Due to the blockade of D2 receptors in the central nervous system, D2 receptor antagonists like metoclopramide and antipsychotics can also produce a variety of additional side effects including drowsiness, akathisia, restlessness, insomnia, lassitude, fatigue, extrapyramidal symptoms, dystonia, Parkinsonian symptoms, tardive dyskinesia, and depression.
[2][10] However, this is not the case with domperidone, because, unlike other D2 receptor antagonists, it minimally crosses the blood–brain barrier, and for this reason, is rarely associated with such side effects.
[16][17] The risks are dose-dependent, and appear to be greatest with high/very high doses via intravenous administration and in the elderly, as well as with drugs that interact with domperidone and increase its circulating concentrations (namely CYP3A4 inhibitors).
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.However, a 2015 Australian review concluded the following:[18] Based on the results of the two TQT (the regulatory agency gold standard for assessment of QT prolongation) domperidone does not appear to be strongly associated with QT prolongation at oral doses of 20 mg QID in healthy volunteers.
Further, there are limited case reports supporting an association with cardiac dysfunction, and the frequently cited case-control studies have significant flaws.
While there remains an ill-defined risk at higher systemic concentrations, especially in patients with a higher baseline risk of QT prolongation, our review does not support the view that domperidone presents intolerable risk.In Britain, a legal case involved the death of two children of a mother whose three children had all had hypernatraemia.
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.
[9] The drug is a substrate for the P-glycoprotein (ABCB1) transporter, and animal studies suggest that this is the reason for the low central nervous system penetration of domperidone.
[22][21] Janssen pharmacologists discovered that some 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.
[84] In April 2014, the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) published an official press release suggesting restricting the use of domperidone-containing medicines.
It also approved earlier published suggestions by Pharmacovigilance Risk Assessment Committee (PRAC) to use domperidone only for treating nausea and vomiting and reduce maximum daily dosage to 10mg.
[11] Domperidone is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, BANTooltip British Approved Name, and JANTooltip Japanese Accepted Name.
[25] In June 2004, the Food and Drug Administration (FDA) issued a warning that distributing any domperidone-containing products is illegal.
[25] It is available over-the-counter to treat gastroesophageal reflux disease and functional dyspepsia in many countries, such as Ireland, the Netherlands, Italy, South Africa, Mexico, India, Chile, and China.