What are the potential interactions between Diflucan (fluconazole) and Biaxin (clarithromycin)?

From the Guidelines

Diflucan (fluconazole) and Biaxin (clarithromycin) should be used together with caution due to potentially serious drug interactions, particularly the risk of QT interval prolongation and increased fluconazole blood levels. When taken together, these medications can increase the risk of QT interval prolongation, which may lead to dangerous heart rhythm problems, as noted in studies discussing the cardiovascular risks associated with macrolides like clarithromycin 1. Additionally, clarithromycin inhibits the CYP3A4 enzyme system, which can significantly increase fluconazole blood levels, potentially leading to enhanced side effects such as liver damage, nausea, and headaches.

Key Considerations

• Patients taking both medications may require dose adjustments, particularly a reduction in the fluconazole dose, and should be monitored closely for signs of toxicity.
• The interaction between fluconazole and clarithromycin occurs because both drugs compete for metabolism through similar liver enzyme pathways, with clarithromycin blocking the breakdown of fluconazole.
• Patients should inform their healthcare provider about all medications they are taking and report any unusual symptoms such as irregular heartbeat, severe dizziness, or fainting immediately.
• Those with existing heart conditions, electrolyte abnormalities, or liver disease face higher risks from this combination and may need alternative treatment options, as clarithromycin should not be given to patients with a history of QT prolongation or ventricular cardiac arrhythmia 1.

Monitoring and Precautions

• Concomitant administration of clarithromycin with certain drugs is contraindicated due to the risk of QT prolongation and cardiac arrhythmias, including ventricular tachycardia, ventricular fibrillation, and torsades de pointe 1.
• A full clinical and drug history should be undertaken to cover potential drug interactions, emphasizing the importance of careful patient evaluation before initiating therapy with these medications 1.

From the FDA Drug Label

Following administration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily to 21 healthy volunteers, the steady-state clarithromycin C minand AUC increased 33% and 18%, respectively Clarithromycin exposures were increased and steady-state concentrations of 14-OH clarithromycin were not significantly affected by concomitant administration of fluconazole.

The potential interaction between Diflucan (fluconazole) and Biaxin (clarithromycin) is that fluconazole increases clarithromycin exposure. Specifically, the steady-state clarithromycin C min and AUC increase by 33% and 18%, respectively, when fluconazole is administered concomitantly with clarithromycin 2.

From the Research

Potential Interactions between Diflucan and Biaxin

• The potential interactions between Diflucan (fluconazole) and Biaxin (clarithromycin) can be understood by examining their effects on the cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme 3.
• Fluconazole is a moderate inhibitor of the CYP3A4 isoenzyme, while clarithromycin is a strong inhibitor of this enzyme 3.
• When coadministered, these drugs may increase the plasma concentrations of other medications that are metabolized by CYP3A4, potentially leading to increased risk of adverse events 3, 4.
• A study examining the effect of clarithromycin and fluconazole on the pharmacokinetics of montelukast found that clarithromycin increased the plasma concentrations of montelukast, while fluconazole reduced the plasma concentrations of montelukast 4.
• Another study found that fluconazole did not significantly alter the pharmacokinetics of certain medications, such as oral contraceptives, but did affect the pharmacodynamics of warfarin and the pharmacokinetics of phenytoin and cyclosporin A 5.
• Clarithromycin has been shown to be a safe and efficacious choice for the treatment of community-acquired bacterial respiratory tract infections, but its use with other medications that inhibit CYP3A4, such as fluconazole, should be carefully monitored 6.

Clinical Implications

• Patients taking Diflucan and Biaxin concurrently should be closely monitored for potential adverse events, such as increased risk of gastrointestinal toxicity, bone marrow suppression, and multiorgan failure 3.
• Healthcare providers should be aware of the potential for drug-drug interactions between these medications and take steps to minimize the risk of adverse events, such as adjusting doses or selecting alternative therapies 3, 4.