Prokinetic / antiemetic (peripheral dopamine antagonist)
Domperidone is a medicine used to relieve nausea and vomiting and the feeling of fullness, upper abdominal discomfort and regurgitation. It acts on the stomach and gut without crossing the blood-brain barrier, so it causes fewer nervous system effects than metoclopramide. Because of the risk of cardiac arrhythmias, it should be used at the lowest effective dose for the shortest possible time.
Also known as: Motilium, domperidone
Ciprofloxacin may increase domperidone exposure and add QT-interval effects.
Domperidone, a prokinetic antiemetic, prolongs the QT interval and is associated with torsade de pointes, especially at high doses or with risk factors; ciprofloxacin belongs to the fluoroquinolone class with the same effect. The combination adds up the risk of ventricular arrhythmias, particularly in the elderly, patients with cardiac disease, hypokalaemia or taking other QT-prolonging drugs. Whenever possible, choose an antibiotic without QT effect or an alternative antiemetic; if unavoidable, monitor the ECG and electrolytes.
Ciprofloxacin + domperidone: additive risk of QT prolongation. Avoid in at-risk patients.
Ciprofloxacin partially inhibits CYP3A4 and both prolong the QT.
Monitor ECG in patients with risk factors (hypokalaemia, bradycardia, other QT drugs).
Ventricular arrhythmias, torsade de pointes (rare).
Use with caution; consider an alternative if QT risk factors are present.
DailyMed (FDA) — approved Domperidone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cdb0c9b9-388c-4a06-9fe9-bb4e52278a4e ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c527d138-e32c-418f-9573-a3d8a796279f — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Combining domperidone with clarithromycin is contraindicated: clarithromycin inhibits CYP3A4 and raises domperidone concentrations, with a high risk of QT-interval prolongation and torsade de pointes.
Domperidone prolongs the QT interval and is metabolised by CYP3A4; clarithromycin, a potent inhibitor of this isoenzyme, raises its concentrations and the risk of malignant ventricular arrhythmias (torsades de pointes). For this reason, the combination is formally contraindicated. The risk is higher in patients with heart disease, hypokalaemia, bradycardia or taking other QT-prolonging drugs; an alternative prokinetic or antibiotic should be chosen.
Contraindication: clarithromycin inhibits CYP3A4 and raises domperidone concentrations, increasing the risk of QT prolongation and torsades de pointes. Do not combine; choose an alternative.
Clarithromycin is a potent CYP3A4 inhibitor, the main metabolic pathway of domperidone; both substances prolong the QT interval.
Monitor ECG (QT interval) and arrhythmia symptoms (palpitations, syncope).
Torsade de pointes, sudden death.
Avoid the combination; choose an alternative macrolide or a prokinetic/antiemetic without QT risk.
DailyMed (FDA) — approved Domperidone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cdb0c9b9-388c-4a06-9fe9-bb4e52278a4e ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Domperidone should be taken before meals to optimise the prokinetic effect.
Take 15–30 minutes before meals.
EMC-UK (MHRA) — approved Domperidone SmPC: https://www.medicines.org.uk/emc/product/3188/smpc
Domperidone prolongs the QT interval and is contraindicated when the QT is already prolonged.
Do not use in patients with QT prolongation or QT-prolonging drugs.
EMC-UK (MHRA) — approved Domperidone SmPC: https://www.medicines.org.uk/emc/product/3188/smpc
Domperidone is contraindicated in moderate to severe hepatic impairment due to an increased risk of QT prolongation.
Do not use in moderate to severe hepatic impairment.
EMC-UK (MHRA) — approved Domperidone SmPC: https://www.medicines.org.uk/emc/product/3188/smpc
Data on domperidone in pregnancy are limited; use only if the benefit outweighs the risk.
Avoid in the 1st trimester unless strictly necessary.
Excreted into breast milk in small amounts; compatible with breastfeeding at usual doses.
No specific additional contraception.
EMC-UK (MHRA) — approved Domperidone SmPC: https://www.medicines.org.uk/emc/product/3188/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Prokinetic and antiemetic, peripheral dopamine D2 receptor antagonist, without relevant blood-brain barrier crossing (low incidence of extrapyramidal effects). Increases gastric motility and duodenal peristalsis. Risk of QT prolongation and ventricular arrhythmias — contraindicated with potent CYP3A4 inhibitors and in patients with QT prolongation; oral bioavailability ~15% (first-pass effect) and half-life 7-9 h.
Peripheral dopamine D2 receptor antagonist; the low blood-brain barrier crossing explains the low incidence of extrapyramidal effects. The prokinetic effect results from increased upper GI motility (gastric tone and amplitude of contractions, pyloric relaxation, duodenal peristalsis) and lower oesophageal sphincter tone.
Under fasting conditions, rapid oral absorption with peak plasma concentrations at 30-60 minutes. The low absolute oral bioavailability (~15%) is due to extensive first-pass metabolism in the gut wall and liver. Taking after a meal increases bioavailability; reduced gastric acidity impairs absorption. Plasma protein binding 91-93%.
Rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation; CYP3A4 is the major cytochrome P450 form involved in N-dealkylation, and CYP3A4, CYP1A2 and CYP2E1 are involved in aromatic hydroxylation. Urinary and faecal excretion amount to 31% and 66% of the oral dose, respectively; the proportion excreted unchanged is small (~1% in urine, 10% of faecal excretion).
Plasma half-life of 7-9 hours after a single oral dose in healthy subjects; prolonged in severe renal insufficiency (elimination half-life increased from 7.4 to 20.8 hours in patients with severe renal insufficiency) — reduce the dosing frequency in these patients.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
