Nexium IV is extensively metabolized in the liver by CYP2C19 and CYP3A4.
In vitro and in vivo studies have shown that esomeprazole is not likely to inhibit CYPs 1A2, 2A6, 2C9,
2D6, 2E1 and 3A4. No clinically relevant interactions with drugs metabolized by these CYP enzymes would be expected.
Drug interaction studies have shown that esomeprazole does not have any clinically significant interactions with
phenytoin, warfarin, quinidine, clarithromycin or amoxicillin. Post-marketing reports of changes in prothrombin
measures have been received among patients on concomitant warfarin and esomeprazole therapy. Increases in INR and
prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and
warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Nexium IV may potentially interfere with CYP2C19, the major esomeprazole metabolizing enzyme.
Coadministration of esomeprazole 30 mg and diazepam, a CYP2C19 substrate, resulted in a 45% decrease in clearance of
diazepam. Increased plasma levels of diazepam were observed 12 hours after dosing and onwards. However, at that time,
the plasma levels of diazepam were below the therapeutic interval, and thus this interaction is unlikely to be of
Nexium IV inhibits gastric acid secretion. Therefore, esomeprazole may interfere with the
absorption of drugs where gastric pH is an important determinant of bioavailability (eg, ketoconazole, iron salts and
Coadministration of oral contraceptives, diazepam, phenytoin, or quinidine did not seem to change the
pharmacokinetic profile of esomeprazole.
Combination Therapy with Clarithromycin
Co-administration of esomeprazole, clarithromycin, and amoxicillin has resulted in increases in the
plasma levels of esomeprazole and 14-hydroxyclarithromycin.
Concomitant administration of clarithromycin with pimozide is contraindicated.