Fluconazole with Tretinoin Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Tretinoin
- Tretinoin
- Vesanoid®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
An increased risk of tretinoin toxicity and an increased risk of CNS-related undesirable effects (such as pseudotumor cerebri)
Interaction Summary
In a case report, CNS-related undesirable effects in the form of pseudotumor cerebri has been developed in one patient receiving combination therapy with all-trans-retinoid acid (an acid form of vitamin A) and fluconazole, which disappeared after discontinuation of fluconazole treatment. This combination may be used but the incidence of CNS-related undesirable effects should be borne in mind. Concurrent use of tretinoin and fluconazole may result in tretinoin toxicity, necessitating a decrease in tretinoin dose .
Severity
Moderate
Onset
Rapid
Evidence
Probable
How To Manage Interaction
Concomitant use of fluconazole with tretinoin (all-trans-retinoic acid) may result in CNS-related undesirable effects (such as pseudotumor cerebri). This combination may be used but the incidence of CNS-related undesirable effects should be borne in mind.
Mechanism Of Interaction
Inhibition of tretinoin metabolism by fluconazole
Literature Reports
A) In a case report, CNS-related undesirable effects in the form of pseudotumor cerebri has been developed in one patient receiving combination therapy with all-trans-retinoid acid (an acid form of vitamin A) and fluconazole, which disappeared after discontinuation of fluconazole treatment .
B) A case has been reported of a patient with tretinoin toxicity thought to be secondary to an interaction with fluconazole. CNS toxicity developed in a 4-year-old male patient with AML during treatment with a therapeutic dose of tretinoin that seems to have been potentiated by concurrent use of fluconazole. The responsible mechanism may be the inhibition of CYP450 system by fluconazole. The patient presented with fatigue, pallor and bruising. Following a diagnosis of APL, induction chemotherapy was begun with cytarabine, daunorubicin, and tretinoin. The patient developed febrile neutropenia and was treated with meropenem from day 2 to 20 of ATRA treatment and amphotericin B from day 14 to 20 for prolonged febrile neutropenia, until recovery of his counts on day 20. Fluconazole 100 mg/d was initiated for fungal prophylaxis on day 20, after discontinuation of amphotericin. On day 21 of tretinoin treatment, the patient complained of a headache. Headache, vomiting and papilledema occurred by day 27. A diagnosis of pseudotumor cerebri (PTC) was made. Tretinoin was discontinued on day 28, and symptoms of increased intracranial pressure resolved within 24 hours. Tretinoin was then restarted on day 30 at 75% of the therapeutic dose which caused headache and vomiting within 2 days, and it was discontinued again. On day 35 tretinoin was restarted at 30% of the therapeutic dose, and by day 38 he had a headache but only one episode of vomiting. Tretinoin was continued at 30% dosing. The patient clinically improved within 24 hours of discontinuation of fluconazole on day 41 with complete resolution of his headache and vomiting. The patient was able to tolerate an increase in tretinoin to full dose once fluconazole was stopped. The author suggests carefully monitoring patients for side effects of tretinoin, when used in conjunction with other medications that affect the cytochrome P450 system .
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.
Tretinoin Overview
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Tretinoin is used to treat acute promyelocytic leukemia (APL; a type of cancer in which there are too many immature blood cells in the blood and bone marrow) in people who have not been helped by other types of chemotherapy or whose condition has improved but then worsened following treatment with other types of chemotherapy. Tretinoin is used to produce remission (a decrease or disappearance of signs and symptoms of cancer) of APL, but other medications must be used after treatment with tretinoin to prevent the cancer from returning. Tretinoin is in a class of medications called retinoids. It works by slowing or stopping the growth of cancer cells by causing immature blood cells to develop into normal blood cells.
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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.