Summary

Rifampin and voriconazole have a clinically significant drug interaction where rifampin dramatically reduces voriconazole plasma concentrations through CYP450 enzyme induction. This interaction can lead to treatment failure of antifungal therapy and is generally considered a contraindication for concurrent use.

Introduction

Rifampin is a potent antibiotic belonging to the rifamycin class, primarily used for treating tuberculosis and other mycobacterial infections. It is known for its strong enzyme-inducing properties affecting hepatic metabolism. Voriconazole is a triazole antifungal medication used to treat serious invasive fungal infections, including aspergillosis and candidemia. It is metabolized primarily through the cytochrome P450 enzyme system, making it susceptible to drug interactions with enzyme inducers like rifampin.

Mechanism of Interaction

The interaction between rifampin and voriconazole occurs through rifampin's potent induction of cytochrome P450 enzymes, particularly CYP2C19, CYP2C9, and CYP3A4. These enzymes are responsible for voriconazole metabolism. When rifampin induces these enzymes, it significantly increases the clearance of voriconazole, leading to dramatically reduced plasma concentrations. Studies have shown that rifampin can decrease voriconazole levels by up to 96%, making the antifungal therapy ineffective.

Risks and Symptoms

The primary clinical risk of this interaction is antifungal treatment failure due to subtherapeutic voriconazole concentrations. This can result in progression of invasive fungal infections, which are often life-threatening conditions. The interaction is so significant that it may render voriconazole completely ineffective, potentially leading to increased morbidity and mortality in patients with serious fungal infections. Additionally, attempting to overcome this interaction by increasing voriconazole doses is generally not recommended due to unpredictable pharmacokinetics and potential toxicity.

Management and Precautions

The concurrent use of rifampin and voriconazole is generally contraindicated and should be avoided whenever possible. If both medications are absolutely necessary, alternative antifungal agents such as liposomal amphotericin B or echinocandins should be considered instead of voriconazole. If rifampin must be used in a patient requiring antifungal therapy, consultation with infectious disease specialists is essential to determine the most appropriate antifungal alternative. Therapeutic drug monitoring cannot reliably overcome this interaction due to the magnitude of the effect. Healthcare providers should carefully review all medications before prescribing either drug to prevent this dangerous interaction.

Rifampin interactions with food and lifestyle

Rifampin should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be avoided or limited while taking rifampin, as both rifampin and alcohol can cause liver toxicity, and the combination may increase the risk of hepatotoxicity. Patients should be counseled to take rifampin consistently either with or without food (preferably without) to maintain consistent blood levels.

Voriconazole interactions with food and lifestyle

Voriconazole should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, as food significantly reduces absorption and bioavailability. High-fat meals can decrease voriconazole absorption by up to 22%. Patients should avoid grapefruit and grapefruit juice during treatment, as these can increase voriconazole blood levels and risk of toxicity. Alcohol consumption should be avoided or limited, as both voriconazole and alcohol are metabolized by the liver and concurrent use may increase the risk of liver toxicity. Patients should also avoid prolonged sun exposure and use adequate sun protection, as voriconazole can cause photosensitivity reactions and increase risk of skin cancer with long-term use.