domperidone
dopamine D2 receptor antagonist, antiemetic and prokinetic· Brands: Motilium, Domperid, Domstal, PeridysPOPR
Mechanism of action
Domperidone competitively blocks dopamine D2 receptors in the chemoreceptor trigger zone (CTZ) of the area postrema and in the gastrointestinal tract. This blockade reduces nausea and vomiting signals to the brain and enhances gastric motility, gastroduodenal coordination, and lower esophageal sphincter tone. Because it poorly penetrates the blood-brain barrier, it has limited central nervous system effects compared with other dopamine antagonists such as metoclopramide.
Pharmacokinetics
Domperidone is administered orally or rectally. Oral bioavailability is low (approximately 15%) due to extensive first-pass metabolism in the liver and gut wall. It is metabolized primarily by CYP3A4, with some involvement of CYP3A5 and CYP2D6. The elimination half-life is about 7 to 8 hours. It is mostly excreted in faeces via biliary elimination, with a minor renal component. The drug's absorption is enhanced in the fasting state. In patients with hepatic impairment, metabolism may be reduced, necessitating dose adjustment or avoidance.
Indications & dosing
Nausea and vomiting
Use the lowest effective dose for the shortest duration due to risk of QT prolongation.
- adult · PO: 10 mg TID · Use the lowest effective dose for the shortest duration due to risk of QT prolongation.
Gastroparesis
Administer before meals. Monitor for cardiac effects.
- adult · PO: 10 mg TID · Administer before meals. Monitor for cardiac effects.
Lactation stimulationoff-label
Off-label use; evidence is limited. Consider risks.
- adult · PO: 10 mg TID · Off-label use; evidence is limited. Consider risks.
Contraindications & precautions
- Prolonged QT interval or known cardiac conduction abnormalities · Risk of serious ventricular arrhythmias.
- Significant electrolyte disturbances, e.g. hypokalaemia, hypomagnesaemia · Exacerbates QT prolongation risk.
- Concurrent use of potent CYP3A4 inhibitors that prolong QT · Increases domperidone levels and QT risk.
- Severe hepatic impairment · Domperidone is extensively metabolised in the liver.
- Prolactinoma · Domperidone raises prolactin levels.
- Known hypersensitivity to domperidone · Avoid in patients with allergic reactions.
- Cardiac disease such as congestive heart failure · Increased risk of arrhythmia.
- Children under 1 year · Not recommended due to risk of extrapyramidal reactions.
- Use the lowest effective dose for the shortest duration.
- Avoid in patients with risk factors for QT prolongation, including bradycardia and family history of long QT syndrome.
- Correct electrolyte disturbances before starting treatment.
- Caution in older adults, as they are more susceptible to QT prolongation and arrhythmias.
- Avoid concurrent use of other QT-prolonging drugs, e.g. fluconazole, erythromycin, amiodarone.
- Monitor for signs of cardiac effects, such as palpitations or syncope.
Adverse effects
- Dry mouth
- Abdominal cramps
- Headache
- Hyperprolactinaemia (galactorrhoea, gynaecomastia)
- QT prolongationserious
- Ventricular arrhythmia, sudden cardiac deathserious
- Extrapyramidal reactions, particularly in childrenserious
- Seizuresserious
Renal & hepatic adjustment
- eGFR 0–29: Avoid use; increased risk of QT prolongation and arrhythmias. (avoid)
- eGFR 30–59: Use with caution; consider dose reduction and ECG monitoring.
- Hepatic impairment (moderate): Avoid use; increased risk of QT prolongation due to reduced metabolism. (avoid)
- Hepatic impairment (severe): Contraindicated. (avoid)
Monitoring, pregnancy & toxicity
- ecg · Baseline and periodically in patients at risk of QT prolongation or receiving other QT-prolonging drugs
- serum electrolytes · Baseline and periodically; correct hypokalaemia and hypomagnesaemia before and during treatment
- clinical response · Assess at each visit to confirm continued need for therapy
- signs of extrapyramidal effects · Monitor for dystonia, akathisia, or parkinsonism, especially in children and young adults
- Pregnancy: Domperidone is not recommended in pregnancy, particularly during the first trimester. If an antiemetic is required, alternative agents with established safety profiles should be considered.
- Toxicity: QT prolongation and ventricular arrhythmias · Discontinue domperidone; monitor ECG, correct electrolyte abnormalities, and provide supportive care
- Toxicity: Extrapyramidal symptoms (dystonia, akathisia) · Stop drug; consider anticholinergic agent such as procyclidine or benzhexol; monitor for resolution
- Toxicity: Neuroleptic malignant syndrome · Discontinue drug, cooling measures, supportive care, and dantrolene or bromocriptine as appropriate; seek specialist advice
Clinical notes
Domperidone is used for the short-term relief of nausea and vomiting, and for gastroparesis. It should be used at the lowest effective dose for the shortest duration, ideally not exceeding one week. It is contraindicated in patients with cardiac conduction abnormalities (QT prolongation), significant electrolyte disturbances, or those taking QT-prolonging drugs or strong CYP3A4 inhibitors. The risk of serious ventricular arrhythmias is dose-related; therefore, daily dose limits apply (e.g., max 30 mg/day in adults). It is not recommended in children or in patients with hepatic impairment. Due to safety concerns, the oral formulations have been restricted or withdrawn in some countries; check local availability and regulations.
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BNF; local formulary