Domperidone interacts with a number of drugs and produces adverse reactions. For instance, ketoconazole and itraconazole are two anti-fungal drugs used to cure the infection; any one of these drugs when used in combination with domperidone, raises the concentration of domperidone in plasma. This adverse reaction is of great concern since both of the medications are used to exclusively treat gastroparesis. Furthermore, the administration of domperidone is also restricted to grapefruit juice.

Domperidone

The domperidone’s fundamental metabolic pathway is through CYP3A4. Both the in vitro as well as in vivo data have shown that simultaneous administration of both drugs adversely restricts the enzyme activity resulting in increased levels of domperidone in plasma. However, the concurrent administration of potent CYP3A4 inhibitors and domperidone has evidently shown the unusual prolongation in QT interval and is therefore contraindicated.

Potent CYP3A4 Inhibitors

Moreover, during the concurrent administration of potent CYP3A4 inhibitors with domperidone, if the patients have shown no prolongation in QT interval, the patient should be closely monitored for possible symptoms and signs of adverse reactions.

The examples of such drugs include “anti-arrhythmics class IA” (such as quinidine and disopyramide), “antiarrhythmics class III” (such as sotalol, ibutilide, dronedarone, dofetilide, amiodarone, etc.), certain calcium antagonists (like verapamil, diltiazem), azole antifungals (e.g., voriconazole, ketoconazole, itraconazole, etc.), certain antimalarial agents (such as halofantrine), certain antifungal agents (such as pentamidine), gastrointestinal drugs (such as dolasetron), certain antibiotics (like moxifloxacin, levofloxacin, etc.), certain antidepressants (such as escitalopram, citalopram), certain antipsychotics (such as sertindole, pimozide, haloperidol, etc.), HIV protease inhibitors (like ritonavir, nelfinavir, saquinavir, indinavir, fosamprenavir, atazanavir, amprenavir), certain anti-cancer medications (like vandetanib, toremifene, etc.), macrolide antibiotics (such as erythromycin, clarithromycin, etc.), as well as other drugs such as telithromycin, nefazodone, methadone, bepridil, aprepitant, etc.

Antisecretory Agents or Antacids

In addition, antisecretory agents or antacids may not be administered simultaneously with domperidone, since it will lead to decreased oral bioavailability of domperidone. However, if both are prescribed and should be taken essentially, the domperidone must be taken before the meal, whereas antisecretory agents (antacids) must be after before the meal.

Intolerance to lactose

Domperidone should be restrained while used in patients with lactose tolerance. Most of the film-coated tablets of domperidone comprise lactose, which is not found suitable for lactose intolerant patients, or individuals with galactose malabsorption, glucose malabsorption, or galactosemia.

Anticholinergic Drugs

The interaction between domperidone and anti-cholinergic drugs, when administered concurrently might antagonize the anti-dyspeptic effects of domperidone.

For instance,  the simultaneous administration of domperidone and atropine will decrease the relaxing outcome of atropine, particularly in the lower oesophageal sphincter; however, it could be minimized or presented with no reversing effect if the atropine is administered prior to the administration of domperidone. The domperidone’s fundamental metabolic pathway is through the “cytochrome P450 isoenzyme CYP3A4”.

The human in vitro data has presented that concurrent use of active molecules that potentially inhibit the isoenzyme CYP3A4, will induce a significant increase in the plasma levels of domperidone. In addition, the potent CYP3A4 inhibitors when co-administered with domperidone, it has shown remarkable as well as clinically relevant changes in QT interval prolongation.

Therefore, it is emphasized that the concurrent use of these drugs should be prohibited in clinical settings. It has been suggested that special cautions should be adopted during the co-administration of potent CYP3A4 inhibitors with domperidone in order to inhibit QT interval prolongation.

Other Drugs

Since domperidone also possesses particular gastro-kinetic effects, it may potentially affect the absorption of “concomitantly orally administered drugs”, such as enteric-coated or sustained-release formulations. However, particularly in patients who have already developed stabilization over the administration of paracetamol or digoxin, the concurrent administration of such drugs with domperidone would not affect the blood levels in such patients.