Fluconazole with Nortriptyline Interaction Details
Brand Names Associated with Fluconazole
- Diflucan®
- Fluconazole
Brand Names Associated with Nortriptyline
- Aventyl®
- Nortriptyline
- Pamelor®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 03, 2023
Interaction Effect
Increased nortriptyline exposure, an increased risk of nortriptyline toxicity and an increased risk of cardiotoxicity (QT interval prolongation, torsades de pointes, cardiac arrest)
Interaction Summary
Coadministration of fluconazole and nortriptyline may increase nortriptyline effects. Nortriptyline has been shown to prolong the QTc interval at the recommended therapeutic dose , and fluconazole use has been associated with case reports of QT prolongation and torsades de pointes . Individual case reports have described increased nortriptyline concentrations and signs of toxicity, including QT prolongation and torsades de pointes, when nortriptyline was used in combination with fluconazole . If concomitant use is required, consider measuring 5-nortriptyline levels prior to initiation of concomitant use and repeat measurement 1 week later. Adjust nortriptyline dosage if necessary .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant administration of fluconazole and nortriptyline may cause increased nortriptyline effects and increase the risk for cardiotoxicity, including QT prolongation and torsades de pointes . If concomitant use is required, consider measuring 5-nortriptyline levels prior to initiation of concomitant use and repeat measurement 1 week later. Adjust nortriptyline dosage if necessary .
Mechanism Of Interaction
Additive QT interval prolongation
Literature Reports
A) A 65-year-old woman taking nortriptyline 75 mg daily had a trough serum level of 149 nanogram/mL (ng/mL; 566 nanomol/L) before addition of fluconazole 200 mg once followed by 100 mg daily. Three days later she appeared to be somewhat sedated. Her drug regimen included cycloSPORINE, morphine, metoclopramide, bumetanide, and nortriptyline. Her morphine dose was decreased, and the nortriptyline dose was decreased to 50 mg daily for 4 days. She became more alert and nortriptyline was resumed at 75 mg daily. Five days later the nortriptyline level was 252 ng/mL (957 nanomol/L); nortriptyline was discontinued .
B) A 57-year-old female presented to an emergency department with complaints of several episodes of loss of consciousness, all occurring while the patient was seated. Chest pressure was present after each episode. Medications included amitriptyline for the previous five weeks, sertraline 100 mg daily for the previous seven months, fluconazole, lisinopril, and an iron supplement. An electrocardiogram (ECG) three months prior to presentation showed a normal sinus rhythm with a normal QT interval. Upon hospital admission, the patient had several episodes of torsades de pointes recorded in leads II and VI that were accompanied by near syncope while the patient was supine. Amitriptyline was discontinued and fluconazole was reduced to 200 mg daily. Follow-up ECGs showed progressive normalization of the QT interval and ECGs three and six months after hospitalization were normal .
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.
Nortriptyline Overview
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Nortriptyline is used to treat depression. Nortriptyline is in a group of medications called tricyclic antidepressants. It works by increasing the amounts of certain natural substances in the brain that are needed to maintain mental balance.
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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.