Summary

Fluconazole and omeprazole have a moderate drug interaction primarily through CYP2C19 enzyme inhibition. Fluconazole can significantly increase omeprazole plasma concentrations, potentially leading to enhanced acid suppression and increased risk of omeprazole-related adverse effects.

Introduction

Fluconazole is a triazole antifungal medication commonly prescribed for treating candidiasis, cryptococcal infections, and other fungal infections. It works by inhibiting fungal cytochrome P450 enzymes, particularly CYP51, which is essential for ergosterol synthesis in fungal cell membranes. Omeprazole belongs to the proton pump inhibitor (PPI) class of medications and is widely used to treat gastroesophageal reflux disease (GERD), peptic ulcers, and other acid-related disorders. It works by irreversibly blocking the H+/K+-ATPase enzyme in gastric parietal cells, effectively reducing stomach acid production.

Mechanism of Interaction

The interaction between fluconazole and omeprazole occurs through competitive inhibition of the cytochrome P450 2C19 (CYP2C19) enzyme system. Fluconazole is a potent inhibitor of CYP2C19, which is the primary enzyme responsible for omeprazole metabolism. When fluconazole inhibits CYP2C19, it significantly reduces the clearance of omeprazole, leading to increased plasma concentrations and prolonged half-life of the PPI. This mechanism can result in omeprazole levels that are 2-4 times higher than normal, depending on the fluconazole dose and individual patient factors such as CYP2C19 genetic polymorphisms.

Risks and Symptoms

The primary clinical risk of this interaction is excessive acid suppression due to elevated omeprazole levels, which may increase the risk of several adverse effects. These include an increased susceptibility to gastrointestinal infections (such as Clostridioides difficile), reduced absorption of vitamin B12, iron, and magnesium, and potential bone fractures with long-term use. Patients may also experience more frequent omeprazole-related side effects such as headache, nausea, diarrhea, and abdominal pain. Additionally, the enhanced acid suppression may affect the absorption of other medications that require acidic conditions for optimal bioavailability, such as certain antifungals, antiretrovirals, and iron supplements.

Management and Precautions

Fluconazole interactions with food and lifestyle

Fluconazole can be taken with or without food as food does not significantly affect its absorption. However, patients should avoid excessive alcohol consumption while taking fluconazole, as both substances can potentially affect liver function. While moderate alcohol intake is generally considered acceptable, patients with liver conditions or those taking fluconazole for extended periods should discuss alcohol use with their healthcare provider. No specific dietary restrictions are required with fluconazole therapy.

Omeprazole interactions with food and lifestyle

Omeprazole should be taken on an empty stomach, preferably 30-60 minutes before meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be limited or avoided while taking omeprazole, as alcohol can increase stomach acid production and counteract the medication's acid-reducing effects. Additionally, alcohol may worsen gastroesophageal reflux disease (GERD) symptoms that omeprazole is treating. Smoking should be avoided or discontinued, as tobacco use increases stomach acid production and can reduce the effectiveness of omeprazole therapy. Patients should also be aware that omeprazole may interact with certain dietary supplements, particularly those containing magnesium, as long-term use of omeprazole can lead to magnesium deficiency.