Domperidone -Drug Interactions- What we know.

DRUG INTERACTIONS

In vivo drug interactions studies have shown that ketoconazole strongly inhibits the CYP3A4-dependent metabolism of domperidone. Pharmacokinetic studies showed 3-10 fold increase in the area under curve (AUC) and the peak concentration (Cmax) of domperidone when ketoconazole was co-administered.
This co-administration resulted also in a prolongation of the QT interval (maximum of 10-20 msec) which was greater than the prolongation observed with ketoconazole alone. QT prolongation was not observed at oral doses of domperidone of up to 160 mg/day, i.e., twice the maximum recommended daily therapeutic dose. It is important to note that cardiac
arrhythmia and death were reported following high parenteral doses of domperidone.
Results of the interaction study should be considered when domperidone is prescribed with CYP3A4 inhibitors (which may increase plasma levels of domperidone) or with drugs that can cause QT prolongation or torsade de pointes, especially in patients at risk for torsade de pointes (see Contraindications, Warnings).
Co-administration of domperidone with potent CYP3A4 inhibitors is contraindicated
Co-administration of domperidone with drugs which prolong the QT interval is contraindicated (see Contraindications, Warnings).
List of QT prolonging drugs:
 Antiarrhythmics class IA (e.g., disopyramide, hydroquinidine, quinidine),
 Antiarrhythmics class III (e.g., amiodarone, dofetilide, dronedarone, ibutilide, sotalol),
 Certain antipsychotics (e.g., haloperidol, pimozide, sentindole),
 Certain antidepressants (e.g., citalopram, escitalopram),
 Certain antibiotics (e.g., erythromycin, levofloxacin, moxifloxacin, spiramycin),
 Certain antifungal agents (e.g., pentamidine),
 Certain antimalarial agents (in particular halofantrine, lumefantrine),
 Certain gastrointestinal agents (e.g., cisapride, dolasetron, prucalopride),
 Certain antihistamines (e.g., mequitazine, mizolastine),
 Certain medicines used in cancer (e.g., toremifene, vandetanib, vincamine),
 Certain other medicines (e.g., bepridil, diphemanil, methadone)
*The list of examples of QT-prolonging drugs may not be exhaustive
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The concomitant administration of anticholinergic drugs may compromise the beneficial effects of DOMPERIDONE (domperidone maleate).
The main metabolic pathway of domperidone is through CYP3A4. In vitro data suggest that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone. Examples of CYP3A4 inhibitors include the following:
 azole antifungals;
 macrolide antibiotics;
 HIV protease inhibitors; and
 nefazodone.
Since domperidone enhances gastric and small intestinal motility, it may accelerate absorption of drugs from the small bowel while slowing absorption of drugs taken up from the stomach, particularly those with sustained release or enteric-coated formulations.
Care should be exercised when domperidone is administered in combination with MAO inhibitors to avoid this drug interaction.
The concomitant administration of domperidone maleate with antacids or H2-receptor blockers does not decrease the absorption of domperidone maleate.

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