Summary

Fluconazole can significantly increase theophylline blood levels by inhibiting its metabolism, potentially leading to theophylline toxicity. This interaction requires careful monitoring and possible dose adjustments when these medications are used together.

Introduction

Fluconazole is a triazole antifungal medication commonly used to treat various fungal infections, including candidiasis and cryptococcal infections. It works by inhibiting fungal cytochrome P450 enzymes. Theophylline is a methylxanthine bronchodilator used primarily for treating asthma and chronic obstructive pulmonary disease (COPD). It has a narrow therapeutic window and requires careful monitoring due to its potential for toxicity.

Mechanism of Interaction

The interaction between fluconazole and theophylline occurs through cytochrome P450 enzyme inhibition. Fluconazole inhibits CYP1A2, the primary enzyme responsible for theophylline metabolism. When CYP1A2 is inhibited, theophylline clearance decreases significantly, leading to increased plasma concentrations and prolonged half-life. This mechanism-based inhibition can result in theophylline levels rising to potentially toxic ranges, even with standard dosing.

Risks and Symptoms

The primary risk of this interaction is theophylline toxicity, which can manifest as nausea, vomiting, headache, insomnia, tremors, and cardiac arrhythmias. In severe cases, seizures and life-threatening cardiovascular complications may occur. The risk is particularly high in elderly patients, those with liver disease, or patients taking other medications that affect theophylline metabolism. Even therapeutic doses of fluconazole can cause clinically significant increases in theophylline levels, making this a major drug interaction requiring immediate attention.

Management and Precautions

When fluconazole and theophylline must be used concurrently, close monitoring is essential. Theophylline serum levels should be checked before starting fluconazole and within 2-3 days after initiation. Consider reducing theophylline dose by 25-50% when starting fluconazole therapy. Monitor patients for signs of theophylline toxicity including CNS symptoms, gastrointestinal effects, and cardiac abnormalities. Alternative antifungal agents with less CYP1A2 inhibition potential should be considered when possible. If fluconazole is discontinued, theophylline levels may decrease, requiring dose readjustment.

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.

Theophylline interactions with food and lifestyle

Theophylline has several important food and lifestyle interactions that patients should be aware of. Caffeine consumption should be limited as both theophylline and caffeine are methylxanthines, and concurrent use can increase the risk of side effects such as nervousness, irritability, and rapid heart rate. High-protein, low-carbohydrate diets may increase theophylline clearance and reduce drug levels, while high-carbohydrate, low-protein diets may decrease clearance and increase drug levels. Charcoal-broiled foods may increase theophylline metabolism and reduce effectiveness. Smoking tobacco significantly increases theophylline clearance, requiring higher doses in smokers, and dose adjustments are needed when patients quit smoking. Alcohol consumption should be limited as it may affect theophylline metabolism. Patients should maintain consistent dietary habits and inform their healthcare provider of any significant dietary changes or smoking status changes, as these may require dose adjustments to maintain therapeutic levels.