Drug interactions with esomeprazole
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Esomeprazole Drug Interactions: Key Mechanisms and Clinical Implications
Esomeprazole and CYP2C19-Mediated Drug Interactions
Esomeprazole is known to inhibit the CYP2C19 enzyme, which can affect the metabolism of drugs that rely on this pathway. For example, when esomeprazole is taken with voriconazole, a drug metabolized mainly by CYP2C19, it can significantly increase voriconazole blood levels, leading to adverse effects such as visual abnormalities. In such cases, dose adjustments and therapeutic drug monitoring are recommended to avoid toxicity . Similarly, esomeprazole increases the systemic exposure of proguanil (a CYP2C19 substrate) and decreases its metabolite cycloguanil, indicating a significant pharmacokinetic interaction . These findings highlight the need for caution when esomeprazole is co-administered with drugs metabolized by CYP2C19.
Esomeprazole and Antidiabetic Drugs
Studies show that at therapeutic doses, esomeprazole does not significantly interact with sulfonylureas (such as tolbutamide and glibenclamide) or with metformin and DPP-4 inhibitors. No changes in hypoglycemic effects or pharmacokinetics were observed at standard doses, suggesting that dose adjustments are not necessary when these drugs are used together. However, at very high doses, esomeprazole can enhance the hypoglycemic effect of sulfonylureas, although this is not relevant at typical clinical doses 14. Additionally, esomeprazole may help reduce gastrointestinal side effects of metformin and DPP-4 inhibitors, making it a preferred PPI in diabetic patients .
Esomeprazole and Antiplatelet Therapy
There has been concern that esomeprazole, by inhibiting CYP2C19, could reduce the effectiveness of clopidogrel, an antiplatelet drug that requires activation by this enzyme. However, clinical studies indicate that esomeprazole does not significantly affect the antiplatelet effect of dual antiplatelet therapy (aspirin and clopidogrel) in patients after percutaneous coronary intervention. The influence of esomeprazole is much less significant than genetic variations in CYP2C19, and no clinically meaningful interaction was observed 68.
Esomeprazole and Other Drug Interactions
- Atogepant: Esomeprazole does not have a clinically meaningful effect on the pharmacokinetics of atogepant, a migraine medication, though it may slightly delay absorption and reduce peak concentration without affecting overall exposure .
- RLY-4008 (FGFR2 inhibitor): Esomeprazole does not significantly alter the pharmacokinetics of RLY-4008, indicating it can be safely co-administered with this cancer therapy .
- Antibiotics: In animal studies, long-term esomeprazole use impairs gastrointestinal motility, and co-administration with antibiotics can worsen intestinal transit delays while improving gastric emptying. This suggests that gut microbiota play a role in esomeprazole-induced GI side effects, and caution is advised when combining PPIs with antibiotics .
Esomeprazole and Inflammation
Inflammation, particularly elevated interleukin-6 (IL-6), can downregulate CYP3A and CYP2C19 activity, further influencing drug interactions with esomeprazole. Predictive models show that both inflammation and esomeprazole can impact the metabolism of drugs processed by these enzymes, especially after surgery or in disease states .
Conclusion
Esomeprazole is generally safe and has a low risk of clinically significant drug interactions at standard doses. However, it can inhibit CYP2C19, affecting the metabolism of certain drugs like voriconazole and proguanil, and may interact with other medications in the presence of inflammation. For most antidiabetic and antiplatelet drugs, esomeprazole does not require dose adjustments. Careful monitoring is recommended when esomeprazole is combined with drugs highly dependent on CYP2C19 metabolism or when used alongside antibiotics or in inflammatory conditions.
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