Citalopram with Fluconazole Interaction Details
Brand Names Associated with Citalopram
- Celexa®
- Citalopram
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
An increased citalopram exposure and an increased risk of QT interval prolongation and serotonin syndrome
Interaction Summary
Concomitant use of drugs known to prolong the QT interval and that are metabolized by CYP2C19, such as citalopram with fluconazole is contraindicated due to a potential for additive effects on QT interval prolongation and an increased risk of serious cardiac adverse events. Also, as fluconazole inhibits the CYP2C19-mediated metabolism of citalopram, increased citalopram exposure and adverse effects including signs and symptoms of serotonin syndrome may result from coadministration. If coadministered, do not exceed citalopram doses of 20 mg/day . Additionally, 2 case reports describe the development of serotonin toxicity in female oncology patients undergoing concomitant administration of citalopram and fluconazole .
Severity
Contraindicated
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concurrent use of drugs known to prolong the QT interval and that are metabolized by CYP2C19, such as citalopram, with fluconazole is contraindicated due to a potential for additive effects on QT interval prolongation and an increased risk of serious cardiac adverse events. Additionally, as fluconazole inhibits the CYP2C19-mediated metabolism of citalopram, increased citalopram exposure and adverse effects, including signs and symptoms of serotonin syndrome, may result from coadministration. If coadministered, do not exceed citalopram doses of 20 mg/day .
Mechanism Of Interaction
Inhibition of CYP2C19-mediated citalopram metabolism by fluconazole; additive QT interval prolongation
Literature Reports
A) A 46-year-old female developed signs and symptoms of serotonin syndrome several weeks after addition of citalopram 20 mg daily for depression while undergoing treatment of Philadelphia-positive acute lymphocytic leukemia prior to an allogeneic stem-cell transplant. Her medications included fluconazole 200 mg daily, dapsone 100 mg daily, acyclovir 800 mg twice daily, esomeprazole 20 mg daily, dexAMETHasone 2.5 mg daily, zolpidem controlled release 12.5 mg nightly as needed, and losartan/hydroCHLOROthiazide 50 mg/12.5 mg daily. The patient presented after 2 weeks of worsening confusion, which was diagnosed as steroid vs methotrexate-induced delirium and treated with OLANZapine 2.5 mg daily and a steroid taper. Eight days later, the patient presented again with worsening confusion and nonconvulsive seizures, and a clinical examination revealed severe perseveration, altered reflexes, impaired memory (short- and long-term), dull affect, and a Memorial Delirium Assessment Scale (MDAS) score of 9/30. After conditions such as central nervous system leukemia and viral encephalitis were ruled out, the patient was diagnosed with serotonin toxicity. Citalopram treatment was discontinued, and phenytoin 300 mg daily plus OLANZapine 2.5 mg daily were initiated. Overall improvement was noted after 24 hours, with a substantial reduction in MDAS score to 2/30 after 2 days and improvement in depression, affect, and walking after 3 days. After 10 days, all psychiatric parameters were normal with no evidence of depression. A postulated mechanism for this interaction included inhibition of CYP2C19 and CYP3A4-mediated citalopram metabolism by fluconazole (a strong CYP2C19 inhibitor and moderate CYP3A4 inhibitor) leading to elevated citalopram concentrations .
B) A 73-year-old female developed signs and symptoms of serotonin toxicity during treatment of mild chronic depression with citalopram 40 mg daily and while undergoing treatment for Burkitt's-like lymphoma diagnosed 3 months prior. Her medications included fluconazole 100 mg daily, clonazePAM 0.5 mg twice daily, levoFLOXacin 500 mg daily, metoprolol XL 100 mg daily, acyclovir 200 mg twice daily, vancomycin 1 gram twice daily, amLODIPine 10 mg daily, valsartan 160 mg daily, and pantoprazole 40 mg daily. Two days after initiation of a routine cycle of lymphoma treatment, the patient developed fever and signs of delirium, including somnolence and disorientation, which were attributed to ifosfamide treatment and did not improve with addition of methylene blue 50 mg every 8 hours and OLANZapine 2.5 mg/hour. A clinical examination revealed psychomotor impairment, disorientation with respect to time and place, absence of spontaneous speech, perplexed affect, dull thought process, and a Memorial Delirium Assessment Scale (MDAS) score of 13/30. The condition worsened over another 3 weeks, and the MDAS score increased to 18/30. After reevaluation, the patient was diagnosed with serotonin toxicity, which was attributed to inhibition of CYP2C19-mediated citalopram metabolism by fluconazole (a strong CYP2C19 inhibitor) leading to elevated citalopram concentrations and adverse events. Within 72 hours of discontinuing citalopram and increasing olanzapine to 7.5 mg daily, substantial improvement in delirium signs and symptoms as well as mood, affect, thought process, and MDAS score (10/30) were noted, and the patient was discharged after 1 week .
Citalopram Overview
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Citalopram is used to treat depression. Citalopram is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance.
Fluconazole Overview
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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.
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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:
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.