Fluoxetine with Terfenadine Interaction Details
Brand Names Associated with Fluoxetine
- Fluoxetine
- Prozac®
- Prozac® Weekly
- Rapiflux®
- Sarafem®
- Selfemra®
- Symbyax® (as a combination product containing Fluoxetine, Olanzapine)
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 11, 2023
Interaction Effect
An increased risk of cardiotoxicity (QT interval prolongation, torsades de pointes, cardiac arrest)
Interaction Summary
Although 2 cases have been reported in which concomitant terfenadine and FLUoxetine resulted in cardiac toxicity in patients with no previous heart disease, a study of 12 healthy males demonstrated no significant pharmacokinetic or pharmacodynamic interaction between FLUoxetine and terfenadine. Terfenadine and FLUoxetine have been reported to cause QT prolongation at therapeutic doses. The administration of terfenadine with any other medication that may prolong the QT interval is contraindicated . Consider ECG assessment and periodic ECG monitoring if initiating treatment with FLUoxetine in patients with risk factors for QT interval prolongation and ventricular arrhythmia. Discontinue FLUoxetine and obtain a cardiac evaluation if patients develop signs or symptoms consistent with ventricular arrhythmia .
Severity
Contraindicated
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Terfenadine and FLUoxetine have been reported to cause QT prolongation at therapeutic doses. The administration of terfenadine with any other medication that may prolong the QT interval is contraindicated. Consider ECG assessment and periodic ECG monitoring if initiating treatment with FLUoxetine in patients with risk factors for QT interval prolongation and ventricular arrhythmia. Discontinue FLUoxetine and obtain a cardiac evaluation if patients develop signs or symptoms consistent with ventricular arrhythmia .
Mechanism Of Interaction
Reduced terfenadine metabolism; additive QT interval prolongation
Literature Reports
A) In a study of 12 healthy male volunteers, FLUoxetine did not inhibit the metabolism of terfenadine. FLUoxetine 60 mg daily was given for nine days. Terfenadine 60 mg was given alone and after eight days of the nine-day FLUoxetine regimen. A high dose of FLUoxetine was given to test the probability of interaction rigorously. Subject were monitored for changes in terfenadine pharmacokinetics and adverse effects. Concomitant FLUoxetine resulted in a slight decrease in terfenadine plasma concentration. In addition, the area under the plasma concentration time curve for terfenadine was significantly decreased by FLUoxetine. No change in blood pressure, heart rate, or cardiac electrographic tracings (EKG) were observed. One subjected reported dizziness after taking terfenadine alone and one subject had an abnormal EKG at baseline and during all observations during the study .
B) A 39-year old woman experienced cardiac toxicity due to a possible interaction of terfenadine and FLUoxetine . The patient's medications included acyclovir, beclomethasone, pseudoephedrine, and ibuprofen. During hospitalization for a substance abuse treatment program, the patient was started on FLUoxetine 40 mg daily, terfenadine 60 mg twice daily, and disulfiram 250 mg daily. Approximately 14 days later, the patient underwent a routine electrocardiogram (ECG) study that revealed a prolonged QT interval of 550 milliseconds. The patient was asymptomatic and had no prior history of heart disease. Terfenadine was discontinued, and an ECG taken one week later revealed a normal QT interval.
C) A case report describes a possible interaction with terfenadine and FLUoxetine in a 41-year-old male who experienced irregular heartbeat, skipped beats, and shortness of breath a month after institution of FLUoxetine 20 mg daily; he had no previous history of heart disease. His drug regimen included FLUoxetine, terfenadine 60 mg twice daily, ibuprofen 800 mg three times daily, misoprostol 100 mcg four times daily, Midrin(R) (acetaminophen 325 mg, dichloralphenazone 100 mg, isometheptene mucate 65 mg) as needed, and ranitidine 150 mg twice daily. A 24-hour Holter monitor showed intermittent frequent sinus tachycardia, three isolated atrial premature contractions, and three couplets. Terfenadine was discontinued and his previously reported symptoms did not reoccur. FLUoxetine is a known enzyme inhibitor and may have inhibited terfenadine metabolism resulting in the cardiac abnormalities seen in this patient .
Fluoxetine Overview
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Fluoxetine is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), some eating disorders, and panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks). Fluoxetine is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. It is also used along with olanzapine (Zyprexa) to treat depression that did not respond to other medications and episodes of depression in people with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Fluoxetine is in a class of medications 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.
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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.