The main metabolic pathway of domperidone is through CYP3A4. In vitro and human data show that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone.
When domperidone was co-administered with potent CYP3A4 inhibitors which have been shown to cause QT interval prolongation, clinically relevant changes in QT intervals were observed. Therefore, co-administration of domperidone with certain drugs is contraindicated (see Contraindications).
Caution should be exercised when domperidone is co-administered with potent CYP3A4 inhibitors which have not been shown to cause QT interval prolongation or drugs which have been shown to cause QT interval prolongation (see Precautions).
Concomitant administration of anticholinergic drugs (e.g., dextromethorphan, diphenhydramine) may antagonize the anti-dyspeptic effect of MOTILIUM.
Theoretically, since MOTILIUM has gastro-kinetic effects, it could influence the absorption of concomitantly orally administered drugs, particularly those with sustained-release or enteric-coated formulations. However, in patients already stabilized on digoxin or paracetamol, concomitant administration of domperidone did not influence the blood levels of these drugs.
MOTILIUM may also be given with: neuroleptics, the action of which it does not potentiate; dopaminergic agonists (bromocriptine, L-dopa), whose unwanted peripheral effects such as digestive disorders, nausea and vomiting it suppresses without counteracting their central properties.