GI Norm Drug Interactions

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.
Concomitant use of the following substances is contraindicated: QTc prolonging medicinal products: Class IA anti-arrhythmics (e.g., disopyramide, hydroquinidine, quinidine); Class III anti-arrhythmics (e.g., amiodarone, dofetilide, dronedarone, ibutilide, sotalol); Certain anti-psychotics (e.g., haloperidol, pimozide, sertindole); 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 medicines (e.g., cisapride, dolasetron, prucalopride); Certain antihistaminics (e.g., mequitazine, mizolastine); Certain medicines used in cancer (e.g., toremifene, vandetanib, vincamine); Other medicines (e.g., bepridil, diphemanil, methadone).
Potent CYP3A4 inhibitors (regardless of their QT prolonging effects): HIV protease inhibitors (e.g., amprenavir, atazanavir, fosamprenavir, indinavir, ritonavir, saquinavir); Systemic azole antifungals (e.g., ketoconazole, fluconazole, voriconazole); Some macrolides (erythromycin, clarithromycin, telithromycin).
Concomitant use of the following substances is not recommended: Calcium antagonists (e.g., diltiazem, verapamil).
Concomitant use of the following substances requires caution in use: Bradycardia- and hypokalemia-inducing drugs, as well as with macrolides involved in QT-interval prolongation, i.e., azithromycin and roxithromycin.
The previously mentioned list of substances is representative and not exhaustive.
Antacids or antisecretory agents lower the oral bioavailability of domperidone hence; they should not be given simultaneously.
Concomitant administration of anticholinergic drugs with domperidone may antagonize the anti-dyspeptic effect of domperidone.
Domperidone reduces the relaxant effect of atropine on the lower esophageal sphincter if given prior to atropine, but it has no reversing effect if atropine is administered first. Since domperidone has gastro-kinetic effects, it may influence the absorption of concomitantly administered oral medicines, particularly those of sustained-release or enteric-coated formulations.
If patients are already stabilized on digoxin, paracetamol or haloperidol, concomitant administration of domperidone does not influence the blood levels of these medicines.
Separate in vivo pharmacokinetic/pharmacodynamic interaction studies with oral ketoconazole or oral erythromycin in healthy subjects confirmed a marked inhibition of domperidone's CYP3A4 mediated first-pass metabolism by these drugs. The combination of oral domperidone 10 mg four times a day and ketoconazole 200 mg twice a day produced a mean QTc prolongation of 9.8 msec over the observation period, with changes at individual time points ranging from 1.2 to 17.5 msec.