Fluconazole with Carbamazepine Interaction Details

Brand Names Associated with Fluconazole

Brand Names Associated with Carbamazepine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 27, 2023

Interaction Effect

Increased carBAMazepine exposure and an increased risk of carBAMazepine toxicity

Interaction Summary

The concomitant use of carBAMazepine, a CYP3A4 substrate, and fluconazole, a CYP3A4 inhibitor, may increase the serum levels of carBAMazepine and increase the risk of toxicity. Coadministration has resulted in a 30% increase in carBAMazepine serum levels. If carBAMazepine is used concomitantly with fluconazole, closely monitor carBAMazepine levels and adjust the carBAMazepine dosage as needed . Several cases of carBAMazepine toxicity attributed to the coadministration of fluconazole have also been reported .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of carBAMazepine, a CYP3A4 substrate, and fluconazole, a CYP3A4 inhibitor, may result in increased carBAMazepine exposure. If coadministering, closely monitor carBAMazepine levels and adjust the carBAMazepine dosage as needed.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of carBAMazepine by fluconazole

Literature Reports

A) A 33-year-old man with mental retardation and a history of seizures had been taking carBAMazepine 400 mg 3 times daily for more than 5 years. His last carBAMazepine concentration before the initiation of fluconazole therapy was 11.1 mcg/mL, which was consistent with his past levels. Fluconazole 150 mg daily, ciprofloxacin 250 mg twice daily, and an oral steroid taper were prescribed for a skin eruption which was thought to be candidiasis. Ciprofloxacin was discontinued after 2 days since no clinical improvement was noted. By the end of the third day of fluconazole therapy, the patient was lethargic and unarousable to painful stimuli. A carBAMazepine concentration was measured at 24.5 mcg/mL. Fluconazole was discontinued and carBAMazepine was held for 24 hours. By the next day, the carBAMazepine concentration was 12.4 mcg/mL and his symptoms had resolved. He was restarted on his prior dose of carBAMazepine and 4 days later had a level of 11.7 mcg/mL .

B) Fluconazole, a CYP inhibitor, inhibits the metabolism of carBAMazepine but undergoes metabolism itself via the CYP3A4 isoenzyme. A 38-year-old mentally retarded man was admitted to the hospital because of coffee ground emesis. His medications included lansoprazole, raNITIdine, carBAMazepine (200 mg 3 times a day and 400 mg at bedtime), cisapride, clonazePAM, docusate, lactulose, dantrolene, and a multivitamin tablet. The serum carBAMazepine level on admission was 6 mcg/mL. CarBAMazepine was increased to 1000 mg/day due to increased seizure activity. On hospital day 24, fluconazole was initiated at 200 mg/day for severe tinea cruris. Three days later, fluconazole was increased to 400 mg/day because blood culture was positive for candida albicans. After 10 days of fluconazole therapy the carBAMazepine level was 18 mg/mL. The patient showed no signs of toxicity. carBAMazepine was decreased to 200 mg 4 times daily which lead to therapeutic carBAMazepine levels. He was discharged on day 45 of hospitalization. This case report suggests that elevations in carBAMazepine serum concentrations can occur with concomitant fluconazole therapy .

C) Addition of fluconazole to a stable drug regimen containing carBAMazepine resulted in an increased carBAMazepine plasma level with associated symptoms of carBAMazepine toxicity (ataxia, nystagmus, diplopia, nausea, vomiting). A 29-year-old woman with a history of partial epilepsy had been taking carBAMazepine 1600 mg/day, lamotrigine 400 mg/day, and barbexaclone 100 mg/day for many years without incident. The carBAMazepine plasma level drawn 3 months prior to initiation of fluconazole was approximately 7.5 mcg/mL. Fluconazole was initiated at 150 mg/day for treatment of tinea corporis. On the first day of fluconazole administration the patient noted episodes of blurred vision and dizziness during head movements. After 11 days of fluconazole therapy the patient complained of severe diplopia, oscillopsia, nausea, vomiting, and gait instability. Lamotrigine and barbexaclone plasma levels remained mostly unchanged, but the carBAMazepine plasma level increased to approximately 18.5 mcg/mL. Neurological exam revealed a gaze-evoked nystagmus and smooth pursuit impairment. Twenty-four hours after fluconazole withdrawal, carBAMazepine plasma levels decreased to approximately 8 mcg/mL and neurological symptoms improved .

D) Fluconazole inhibits the metabolism of carBAMazepine and an increase in serum carBAMazepine of 30% has been observed .

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.

Carbamazepine Overview

• Carbamazepine is used alone or in combination with other medications to control certain types of seizures in people with epilepsy. It is also used to treat trigeminal neuralgia (a condition that causes facial nerve pain). Carbamazepine extended-release capsules (Equetro brand only) are also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen at the same time) in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in the brain.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.