Amitriptyline with Fluconazole Interaction Details

Brand Names Associated with Amitriptyline

Brand Names Associated with Fluconazole

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

Interaction Effect

Increased amitriptyline exposure, an increased risk of amitriptyline toxicity and an increased risk of cardiotoxicity (QT interval prolongation, torsades de pointes, cardiac arrest)

Interaction Summary

Coadministration of fluconazole and amitriptyline may increase amitriptyline effects . Several case reports have described increased amitriptyline concentrations and signs of toxicity, including QT prolongation and torsades de pointes, when amitriptyline was used in combination with fluconazole . If concomitant use is required, measure S-amitriptyline levels prior to initiation of concomitant use and repeat measurement 1 week later. Adjust amitriptyline dosage if necessary .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant administration of amitriptyline and fluconazole may cause increased amitriptyline effects and an increased risk for cardiotoxic reactions, including QT prolongation and torsades de pointes. If concomitant use is required, consider measuring S-amitriptyline levels prior to initiation of concomitant use and repeat measurement 1 week later. Adjust amitriptyline dosage if necessary .

Mechanism Of Interaction

Additive QT interval prolongation

Literature Reports

A) Three case reports describe increased amitriptyline levels with fluconazole. Patient 1, a 39-year-old male, was taking fluconazole 200 mg daily and amitriptyline 25 mg three times daily. Three days after amitriptyline was increased to 50 mg three times daily to treat neuropathic pain, the patient experienced visual hallucinations and had a serum amitriptyline level of 724 ng/mL (therapeutic level, 150 ng/mL to 250 ng/mL). Patient 2, a 35-year-old male, was taking amitriptyline 50 mg per day. After fluconazole 100 mg daily was added following a loading dose of 200 mg, the patient had a serum amitriptyline level of 349 ng/mL on day 33 of combined therapy. The patient did not experience any behavioral changes. Patient 3, a 43-year-old male with end-stage renal disease, had received amitriptyline 100 mg per day for over a year. After receiving fluconazole doses of 200 mg to 400 mg daily for five days after a loading dose of 1000 mg, the patient's serum amitriptyline level was 1224 ng/mL. The patient experienced cardiac arrest eight days later and died after a complicated hospital course. In all of the cases, patients were on several other continuous medications. The authors suggest that the addition of fluconazole caused increases in serum amitriptyline, possibly due to fluconazole-induced inhibition of cytochrome P450 isozymes .

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 .

C) A 12-year-old boy with prostatic rhabdomyosarcoma experienced temporary loss of consciousness associated with concomitant fluconazole and amitriptyline treatment. The syncopal episodes occurred periodically over approximately seven months, and coincided with the addition of fluconazole to his drug regimen which included amitriptyline. The patient previously tolerated each medication when given exclusively. The patient experienced no further episodes of syncope after amitriptyline was discontinued .

Amitriptyline Overview

• Amitriptyline is used to treat symptoms of depression. Amitriptyline is in a class 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.

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.

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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.