What are the contraindications for domperidone?

Domperidone Contraindications

Domperidone is absolutely contraindicated in patients with pre-existing QT prolongation, electrolyte abnormalities (hypokalemia, hypomagnesemia), concurrent use of QT-prolonging medications, gastrointestinal obstruction, and hypersensitivity to the drug. 1, 2, 3

Absolute Contraindications

Cardiac Contraindications

• Pre-existing QT prolongation or Long QT Syndrome (LQTS) is an absolute contraindication due to domperidone's potent hERG channel inhibition at clinically relevant concentrations, which significantly increases risk of torsade de pointes and sudden cardiac death 1, 2, 4
• Concurrent use of medications that prolong the QT interval must be avoided, as this dramatically increases the risk of fatal ventricular arrhythmias 1, 2, 4
• Concurrent use of CYP3A4 inhibitors (such as erythromycin and ketoconazole) is contraindicated, as these drugs cause multi-fold increases in domperidone exposure, substantially elevating cardiac risk 3, 4

Electrolyte Abnormalities

• Hypokalemia and hypomagnesemia are absolute contraindications, as electrolyte disturbances further destabilize cardiac repolarization and amplify proarrhythmic potential 1, 2, 4

Gastrointestinal Contraindications

• Gastrointestinal obstruction or blockage (suspected or confirmed) is an absolute contraindication because domperidone is a prokinetic agent that stimulates gut motility, which could worsen obstruction 3
• Gastrointestinal hemorrhage precludes use due to the risk of exacerbating bleeding through increased motility 5

Other Absolute Contraindications

• Hypersensitivity or allergy to domperidone 3, 5
• Presence of a prolactinoma, as domperidone causes prolactinemia through dopamine-2 receptor antagonism 5, 6
• Pregnancy and breastfeeding require extreme caution; in veterinary use, domperidone administered more than 15 days before expected delivery may cause premature birth, low birth weight, or neonatal morbidity 3

Relative Contraindications and High-Risk Situations

Patients Requiring Intensive Monitoring

• Any patient with risk factors for QT prolongation should be considered at high risk, as domperidone demonstrates a safety ratio of only 5.25 (far below the minimum acceptable safety ratio of 30), meaning therapeutic concentrations are dangerously close to proarrhythmic concentrations 7
• The European Medicines Agency recommends against long-term use of prokinetic agents like domperidone due to serious adverse effect risks 2

Clinical Context

• While domperidone may improve early satiety in cancer patients, clinicians must be aware of its potential adverse effects on cardiac rhythm, particularly QT prolongation and torsade de pointes 8
• The risk of QT prolongation with usual therapeutic doses of oral domperidone appears low, but intravenous bolus doses carry significantly higher risk 8

Critical Safety Monitoring Requirements

• Regular QTc monitoring via ECG is essential for any patient on domperidone therapy, particularly for long-term use 1, 2
• Baseline ECG should be obtained before initiating therapy to identify pre-existing QT prolongation 5, 4
• Electrolyte panels should be checked and corrected before starting domperidone 5, 4
• Medication reconciliation is mandatory to identify potential drug interactions with CYP3A4 inhibitors or other QT-prolonging agents 3, 4

Important Clinical Pitfalls

• Domperidone is not FDA-approved in the United States and is only available through an FDA investigational drug application, reflecting ongoing safety concerns 2
• Despite being available over-the-counter in some countries, domperidone carries significant cardiac risks that are often underappreciated; it should not be considered an "innocent" relief medication 7
• The compound's preclinical data unambiguously demonstrate marked hERG channel inhibition, action potential prolongation, and proarrhythmic potential at clinically relevant concentrations 4, 7