Fluconazole with Flibanserin Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Flibanserin
- Addyi®
- Flibanserin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 27, 2023
Interaction Effect
Increased flibanserin exposure and flibanserin adverse effects (hypotension, syncope, sedation)
Interaction Summary
Concomitant use of flibanserin, a CYP3A4 substrate, and a strong or moderate CYP3A4 inhibitor increases flibanserin concentrations, which may result in hypotension, syncope, or CNS depression (eg, sedation, somnolence). In pharmacokinetic studies, coadministration of flibanserin with the strong CYP3A4 inhibitors, ketoconazole and itraconazole increased flibanserin exposure by 4.5-fold and 2.6-fold, respectively. Coadministration of flibanserin with fluconazole (a moderate CYP3A4 inhibitor, moderate CYP2C9 inhibitor, and a strong CYP2C19 inhibitor) and grapefruit juice (moderate CYP3A4 inhibitors) increased flibanserin exposure by 7-fold and 1.4-fold, respectively. In the studies of ketoconazole and fluconazole, more subjects who received flibanserin concomitantly with the CYP3A4 inhibitor experienced hypotension or syncope compared with those who received flibanserin or the CYP3A4 inhibitor alone. Therefore, concurrent use of flibanserin with a strong or moderate CYP3A4 inhibitor is contraindicated. If coadministration is required, flibanserin should be discontinued at least 2 days before initiating the strong or moderate CYP3A4 inhibitor. In addition, the strong or moderate CYP3A4 inhibitor should be discontinued for 2 weeks prior to initiating or restarting flibanserin.
Severity
Contraindicated
Onset
Rapid
Evidence
Theoretical
How To Manage Interaction
Concomitant use of flibanserin and a strong or moderate CYP3A4 inhibitor is contraindicated due to increased flibanserin concentrations, which may result in hypotension, syncope, or CNS depression (eg, sedation, somnolence). If coadministration is required, discontinue flibanserin at least 2 days before initiating the strong or moderate CYP3A4 inhibitor. Discontinue the strong or moderate CYP3A4 inhibitor for 2 weeks prior to initiating or restarting flibanserin.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated flibanserin metabolism
Literature Reports
A) In a pharmacokinetic study of 24 healthy female subjects, coadministration of a single 50-mg dose of flibanserin with ketoconazole (a strong CYP3A4 inhibitor) 400 mg given once daily for 5 days following a light breakfast increased flibanserin AUC(0 to infinity) a significant 4.5-fold and Cmax a significant 1.8-fold compared with flibanserin 50 mg administered alone. Syncope was reported in 1 of 24 (4%) subjects who received concomitant flibanserin and ketoconazole, in 1 of 24 (4%) subjects who received flibanserin alone, and in no subjects who received ketoconazole alone in this study .
B) In a pharmacokinetic study of 12 healthy male and female subjects, coadministration of a single 50-mg dose of flibanserin given 2 hours after 5 days of itraconazole (a strong CYP3A4 inhibitor) 400 mg loading dose followed by 4 days of 200 mg once daily increased flibanserin AUC (0 to infinity) a significant 2.6-fold and Cmax a significant 1.7-fold compared with flibanserin 50 mg alone. The 200-mg itraconazole dose does not maximally inhibit the CYP3A4 enzyme .
C) In a pharmacokinetic study of 15 healthy female subjects, coadministration of a single 100-mg dose of flibanserin with fluconazole (a moderate CYP3A4 inhibitor, moderate CYP2C9 inhibitor, and a strong CYP2C19 inhibitor) 400-mg loading dose followed by 200 mg once daily for 5 days increased flibanserin AUC(0 to infinity) a significant 7-fold and Cmax a significant 2.2-fold compared with flibanserin 100 mg alone. The study was stopped early, because 3 of 15 subjects (20%) who received concomitant fluconazole and flibanserin experienced hypotension or syncope requiring a supine position with legs elevated compared with no such events in subjects treated with flibanserin or fluconazole alone. One of these 3 subjects became unresponsive with a blood pressure of 64/41 mmHg and required treatment with IV saline in the hospital emergency department .
D) In a pharmacokinetic study of 26 healthy female subjects, coadministration of a single 100-mg dose of flibanserin with 240 mL of grapefruit juice (a moderate CYP3A4 inhibitor) increased flibanserin AUC(0 to infinity) by 1.4-fold and Cmax 1.1-fold compared with flibanserin 100 mg alone .
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.
Flibanserin Overview
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Flibanserin is used to treat women with hypoactive sexual desire disorder (HSDD; a low sexual desire that causes distress or interpersonal difficulty) who have not experienced menopause (change of life; the end of monthly menstrual periods). Flibanserin should not be used for the treatment of HSDD in women who have gone through menopause or in men or to improve sexual performance. Flibanserin is in a class of medications called a serotonin receptor 1A agonist/serotonin receptor 2A antagonist. It works by changing the activity of serotonin and other natural substances 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:
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.