Fluconazole with Clarithromycin Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Clarithromycin
- Biaxin® Filmtab®
- Biaxin® Granules
- Biaxin® XL Filmtab
- Biaxin® XL Pac
- Clarithromycin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
Increased clarithromycin exposure and an increased risk of cardiotoxicity (QT interval prolongation, torsades de pointes, cardiac arrest)
Interaction Summary
Concomitant use of fluconazole with other drugs that are known to prolong the QT interval and are CYP3A4 substrates, such as clarithromycin, is contraindicated because of increased exposure to the CYP3A4 substrate and risk for additive QT-interval prolongation. Fluconazole-mediated CYP3A4 inhibition may continue for 4 to 5 days after discontinuation because of the long half-life. Case reports have described QT prolongation and torsades de points associated with fluconazole . Clarithromycin-associated QT prolongation and ventricular arrhythmias have been reported in postmarketing experience and fluconazole increased plasma levels of clarithromycin in 21 subjects .
Severity
Contraindicated
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant use of fluconazole with other drugs that are known to prolong the QT interval and are CYP3A4 substrates, such as clarithromycin, is contraindicated because of increased exposure to the CYP3A4 substrate and risk for additive QT-interval prolongation. Fluconazole-mediated CYP3A4 inhibition may continue for 4 to 5 days after discontinuation because of the long half-life.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated clarithromycin metabolism by fluconazole; additive effects on QT interval prolongation
Literature Reports
A) Simultaneous oral administration of fluconazole 200 mg daily and clarithromycin 500 mg twice daily resulted in an increase in minimum plasma concentration (Cmin) of clarithromycin of 33% and area under the concentration-time curve (AUC) of 18% in 21 healthy subjects. Concomitant administration of fluconazole did not result in a significant change in steady-state concentrations of 14-OH clarithromycin .
B) A prolonged QT interval and torsade de pointes occurred in a 59-year-old female with hepatic cirrhosis and Candida albicans peritonitis receiving intravenous fluconazole (400 to 800 milligrams (mg) daily for 5 weeks) followed by intraperitoneal fluconazole (150 mg daily for 2 days). Within 24 hours of the second intraperitoneal administration, the patient experienced palpitations, premature ventricular contractions (PVCs), and syncope. Electrocardiogram recordings demonstrated polymorphic PVCs, T-wave inversions, and a prolonged time-corrected QT interval of 606 milliseconds. Torsade de pointes tachycardia ensued, requiring cardiopulmonary resuscitation. During this period, an elevated fluconazole plasma level of 216 micrograms/ milliliter was noted. The arrhythmia resolved and QT interval normalized over 3 days following fluconazole discontinuation. No evidence for electrolyte imbalance or organic causes could be determined. The authors conclude that QT prolongation was a direct effect of fluconazole, due to the time course of events and the fact that the patient was receiving no other QT prolonging agents. Although the patient's renal function is not reported, a decline related to cirrhosis may have contributed to drug accumulation. The intraperitoneal route may lead to increased absorption through an inflamed peritoneal membrane .
C) A 25-year-old woman post-mitral valve replacement developed candida albicans sepsis which was treated with high-dose fluconazole (800 mg/day). The patient was on amiodarone for monomorphic ventricular tachycardia following mitral valve replacement surgery. After three days of fluconazole, she developed 2 episodes of torsades de pointes, the second associated with loss of consciousness. Amiodarone was discontinued, then after another episode, fluconazole was replaced by caspofungin. The arrhythmia resolved within 3 days. Risk factors the patient had for development of torsades included female sex, hypokalemia, hypomagnesemia, diuretic use, previous ventricular arrhythmias, and bradycardia .
Fluconazole Overview
-
Fluconazole is used to treat fungal infections, including yeast infections of the vagina, mouth, throat, esophagus (tube leading from the mouth to the stomach), abdomen (area between the chest and waist), lungs, blood, and other organs. Fluconazole is also used to treat meningitis (infection of the membranes covering the brain and spine) caused by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become infected because they are being treated with chemotherapy or radiation therapy before a bone marrow transplant (replacement of unhealthy spongy tissue inside the bones with healthy tissue). Fluconazole is in a class of antifungals called triazoles. It works by slowing the growth of fungi that cause infection.
Clarithromycin Overview
-
Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.
-
Antibiotics such as clarithromycin will not work for colds, flu, or other viral infections. Taking antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.