Summary

Fluconazole can significantly increase losartan plasma concentrations by inhibiting CYP2C9-mediated metabolism, potentially leading to enhanced hypotensive effects. This interaction is considered clinically significant and requires careful monitoring when both medications are used concurrently.

Introduction

Fluconazole is a triazole antifungal medication commonly prescribed for treating various fungal infections, including candidiasis and cryptococcal infections. It works by inhibiting fungal cytochrome P450 enzymes, particularly CYP51. Losartan is an angiotensin II receptor blocker (ARB) used primarily for treating hypertension and diabetic nephropathy. It is a prodrug that requires metabolic conversion to its active metabolite, losartan carboxylic acid (E-3174), primarily through the CYP2C9 enzyme system.

Mechanism of Interaction

The interaction between fluconazole and losartan occurs through cytochrome P450 enzyme inhibition. Fluconazole is a potent inhibitor of CYP2C9, the primary enzyme responsible for converting losartan to its active metabolite E-3174. When fluconazole inhibits CYP2C9, it reduces the formation of the active metabolite while increasing plasma concentrations of the parent compound losartan. This alteration in metabolism can lead to changes in the overall pharmacological effect, as both the parent drug and metabolite contribute to losartan's antihypertensive activity, though through different mechanisms and potencies.

Risks and Symptoms

The primary clinical risk of this interaction is an enhanced hypotensive effect, which may manifest as excessive blood pressure reduction, dizziness, lightheadedness, or orthostatic hypotension. Patients may experience symptoms such as fatigue, weakness, or fainting, particularly when standing up quickly. The risk is generally considered moderate, as the interaction can lead to clinically significant changes in blood pressure control. Elderly patients, those with pre-existing hypotension, or patients taking multiple antihypertensive medications may be at higher risk for adverse effects. The interaction typically develops within days of starting concurrent therapy and may persist for several days after discontinuing fluconazole due to its long half-life.

Management and Precautions

When concurrent use of fluconazole and losartan is necessary, close monitoring of blood pressure is essential, particularly during the first few days of combination therapy. Consider reducing the losartan dose by 25-50% when initiating fluconazole, with subsequent dose adjustments based on blood pressure response. Patients should be counseled about potential symptoms of hypotension and advised to change positions slowly to minimize orthostatic effects. Regular blood pressure monitoring, both in clinical settings and through home monitoring when appropriate, is recommended. If possible, consider alternative antifungal agents with less CYP2C9 inhibition potential, such as terbinafine for appropriate indications. Healthcare providers should review all concurrent medications for additional interactions and ensure patients understand the importance of reporting any concerning symptoms promptly.

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.

Losartan interactions with food and lifestyle

Losartan may interact with potassium-rich foods and salt substitutes containing potassium. Patients should avoid excessive consumption of high-potassium foods (such as bananas, oranges, potatoes, and spinach) and potassium-containing salt substitutes, as this combination may lead to dangerous elevations in blood potassium levels (hyperkalemia). Alcohol consumption should be limited as it may enhance the blood pressure-lowering effects of losartan, potentially causing excessive drops in blood pressure, dizziness, or fainting. Patients should also maintain adequate hydration and avoid becoming dehydrated, especially during hot weather or exercise, as dehydration can increase the risk of kidney problems when taking losartan.