Fluoxetine with Amoxapine Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Amoxapine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 11, 2023

Interaction Effect

Increased risk of tricyclic antidepressant toxicity, QT interval prolongation and serotonin syndrome

Interaction Summary

FLUoxetine, a potent CYP2D6 inhibitor, is associated with an increased risk of serotonin syndrome, QT prolongation, and ventricular arrhythmias (including torsade de pointes). Concomitant therapy with CYP2D6-metabolized tricyclic antidepressants (TCAs) may potentiate these risks and introduce TCA toxicity; concurrent use of FLUoxetine and desipramine, nortriptyline, and imipramine has resulted in significant increases in TCA concentrations . Use caution with concurrent administration of FLUoxetine and TCAs. If FLUoxetine is added to an existing TCA regimen, consider TCA dose reduction. If FLUoxetine and a TCA are coadministered or FLUoxetine has been recently discontinued, consider plasma TCA monitoring. If serotonin syndrome occurs, immediately discontinue FLUoxetine and TCA. If ventricular arrhythmias develop, consider FLUoxetine discontinuation and cardiac evaluation .

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Use caution with concurrent administration of FLUoxetine and TCAs, as elevated TCA plasma concentrations may occur. If FLUoxetine is added to an existing TCA regimen, consider TCA dose reduction. If FLUoxetine and a TCA are coadministered or FLUoxetine has been recently discontinued, consider plasma TCA monitoring. If serotonin syndrome occurs, immediately discontinue FLUoxetine and TCA. If ventricular arrhythmias develop, consider FLUoxetine discontinuation and cardiac evaluation.

Mechanism Of Interaction

Reduced CYP2D6-mediated metabolism by FLUoxetine; additive QT interval prolongation; additive serotonergic effects

Literature Reports

A) Previously stable plasma levels of imipramine and desipramine rose more than 2- to 10-fold with FLUoxetine coadministration in 2 clinical studies. This effect may persist for 3 weeks or more after FLUoxetine discontinuation. Dose reduction and temporary monitoring of tricyclic antidepressant plasma concentrations may be indicated with concurrent FLUoxetine treatment or recent FLUoxetine discontinuation .

B) FLUoxetine statistically and clinically significantly increased desipramine concentrations in 18 healthy subjects. When FLUoxetine (20 mg daily) was added to desipramine (50 mg daily), the mean maximum concentration of desipramine increased by 278% and the AUC increased by 342%. Desipramine trough concentrations continued to be 198% above baseline 3 weeks after FLUoxetine was discontinued. The same study compared pharmacokinetics of desipramine when combined with sertraline. The impact of sertraline was modest, resulting in small and short-term increases in desipramine plasma concentrations .

C) Concomitant administration of FLUoxetine and desipramine was reported to result in an increased desipramine level and new onset of delirium in a 69-year-old male within 10 days of the addition of FLUoxetine to the patient's regimen .

D) FLUoxetine increased the level of tricyclic antidepressants (nortriptyline, imipramine, desipramine) in 4 patients. After the addition of FLUoxetine, the ratio of antidepressant level to dose increased by 109% to 486% in the patients. Three patients developed clinical symptoms (anticholinergic effects, constipation, urinary hesitancy, sedation, unstable gait) as a result of the increased levels .

E) A 39-year-old female experienced symptomatic increases in her desipramine levels with concomitant FLUoxetine therapy. Prior to FLUoxetine therapy, the patient's measured levels of desipramine had ranged from 148 to 160 nanograms/milliliter (ng/mL; 556 to 601 nanomol/L) on a regimen of 300 mg daily. Five weeks after the addition of FLUoxetine 20 mg daily, she reported anticholinergic symptoms, sedation, and confusion with a desipramine level of 527 ng/mL (1978 nanomol/L). The desipramine dose was lowered to 200 mg/day; 11 days later, the level was 244 ng/mL (916 nanomol/L); the patient reported decreased energy, impaired short-term memory, and some "garbled" speech, as well as an episode of nausea, dizziness, and syncope. The desipramine dose was reduced to 50 mg/day, and the adverse effects resolved in 6 days. Eight days later, the desipramine level was 122 ng/mL (458 nanomol/L) .

F) A 33-year-old depressed male developed adverse effects of dry mouth, tinnitus, and difficulties with alertness and memory while receiving FLUoxetine 40 mg daily and desipramine 150 mg daily for 5 weeks; FLUoxetine was discontinued and the blood levels of desipramine decreased from 938 to 48 nanograms/mL (3521 to 180 nanomol/L) with resolution of clinical symptoms .

G) A 75-year-old female experienced symptomatic increases in her desipramine serum concentrations when FLUoxetine was added. Desipramine serum levels ranged from 109 to 150 ng/mL (409 to 563 nanomol/L) with oral doses of 300 mg at bedtime prior to FLUoxetine therapy. Following the addition of oral FLUoxetine 20 mg daily to the regimen, the desipramine serum level increased to 212 ng/mL (796 nanomol/L) within five days. The FLUoxetine dose was increased to 40 mg/day three days later, and the desipramine serum level was 419 ng/mL (1573 nanomol/L) after four days. A worsening of depression and severe fatigue coincided with the increases in desipramine serum levels. Withdrawal of FLUoxetine and reduction in the desipramine dose to 200 mg daily reduced the desipramine serum level to 231 ng/mL (867 nanomol/L) within two weeks .

Fluoxetine Overview

• 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.

Amoxapine Overview

• Amoxapine is used to treat depression. Amoxapine is in a class of medications called tricyclic antidepressants (TCAs). 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:

• 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.