Sompraz IV Drug Interactions

Effects of esomeprazole on the pharmacokinetics of other drugs: The gastric acid suppression during treatment with esomeprazole IV and other PPIs may decrease or increase the absorption of drugs with a gastric pH dependent absorption. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, itraconazole and erlotinib can decrease while the absorption of drugs such as digoxin can increase during treatment with esomeprazole. Reported concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy subjects increased the bioavailability of digoxin by 10% (up to 30% in two out of ten subjects).
Esomeprazole inhibits CYP2C19, the major esomeprazole metabolizing enzyme. Reported concomitant administration of 30 mg esomeprazole resulted in a 45% decrease in clearance of the CYP2C19 substrate diazepam. This interaction is unlikely to be of clinical relevance. Reported concomitant administration of 40 mg esomeprazole resulted in a 13% increase in trough plasma levels of phenytoin in epileptic patients; dose adjustment was not required in this reported study.
Reported concomitant administration of 40 mg esomeprazole to warfarin-treated patients show that, despite a slight elevation in the trough plasma concentration of the less potent R-isomer of warfarin, the coagulation times were within the accepted range.
However, reported post-marketed use cases of elevated INR of clinical significance have been reported during concomitant treatment with warfarin. Close monitoring is recommended when initiating and ending treatment with warfarin or other coumarin derivatives.
Results from reported studies in healthy subjects have shown a pharmacokinetic/pharmacodynamic interaction between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and esomeprazole (40 mg p.o. daily) resulting in decreased exposure to the active metabolite of clopidogrel by an average of 40%, and resulting in decreased maximum inhibition of (ADP induced) aggregation by an average of 14%.
It is, however, uncertain to what extent this interaction is clinically important. Reported one prospective, randomized (but incomplete) study (in over 3,760 patients comparing placebo with omeprazole 20 mg in patients treated with clopidogrel and ASA) and reported non-randomized, post-hoc analyses of data from large, prospective, randomized clinical outcome studies (in over 47,000 patients) did not show any evidence of an increased of risk for adverse cardiovascular outcome when clopidogrel and PPIs, including esomeprazole, were given concomitantly.
Results from a number of reported observational studies are inconsistent with regard to increased risk or no increased risk for CV thromboembolic events when clopidogrel is given together with a PPI.
When clopidogrel was given together with a fixed dose combination of esomeprazole 20 mg + ASA 81 mg compared to clopidogrel alone in a reported study in healthy subjects there was a decreased exposure by almost 40% of the active metabolite of clopidogrel. However, the maximum levels of inhibition of (ADP induced) platelet aggregation in these reported subjects were the same in the clopidogrel and the clopidogrel + the combined (esomeprazole + ASA) product groups, likely due to the concomitant administration of low dose ASA.
Omeprazole as well as esomeprazole act as inhibitors of CYP2C19. Omeprazole, given in doses of 40 mg to healthy subjects in a reported cross-over study, increased C_max and AUC for cilostazol by 18% and 26% respectively, and one of its active metabolites by 29% and 69% respectively.
In healthy volunteers, reported concomitant oral administration of 40 mg esomeprazole resulted in a 32% increase in area under the plasma concentration-time curve (AUC) and a 31% prolongation of elimination half-life (t_½) but no significant increase in peak plasma levels of cisapride. The slightly prolonged QTc interval reported after administration of cisapride alone, was not further prolonged when cisapride was given in combination with esomeprazole.
Concomitant administration of esomeprazole has been reported to increase the serum levels of tacrolimus.
When given together with proton pump inhibitors, methotrexate levels have been reported to increase in some patients. In high-dose methotrexate administration a temporary withdrawal of esomeprazole may need to be considered.
Omeprazole has been reported to interact with some antiretroviral drugs. The clinical importance and the mechanisms behind these reported interactions are not always known. Increased gastric pH during omeprazole treatment may change the absorption of the antiretroviral drug. Other possible interaction mechanisms are via CYP2C19. For some antiretroviral drugs, such as atazanavir and nelfinavir, decreased serum levels have been reported when given together with omeprazole and concomitant administration is not recommended. For other antiretroviral drugs, such as saquinavir, increased serum levels have been reported. There are also some antiretroviral drugs for which unchanged serum levels have been reported when given with omeprazole. Due to the similar pharmacodynamic effects and pharmacokinetic properties of omeprazole and esomeprazole, concomitant administration with esomeprazole and antiretroviral drugs such as atazanavir and nelfinavir is not recommended.
Esomeprazole has been reported to have no clinically relevant effects on the pharmacokinetics of amoxicillin or quinidine.
Effects of other drugs on the pharmacokinetics of esomeprazole: Esomeprazole is metabolized by CYP2C19 and CYP3A4. Reported concomitant oral administration of esomeprazole and a CYP3A4 inhibitor, clarithromycin (500 mg b.i.d.), resulted in a doubling of the exposure (AUC) to esomeprazole. Reported concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP3A4, such as voriconazole, may result in more than doubling of the esomeprazole exposure.
However, those adjustment of esomeprazole is not required in either of these situations.
Drugs known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St. John's wort) may lead to decreased esomeprazole serum levels by increasing the esomeprazole metabolism.