Amitriptyline with Fluvoxamine Interaction Details

Brand Names Associated with Amitriptyline

Brand Names Associated with Fluvoxamine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 13, 2023

Interaction Effect

Increased tricyclic antidepressant exposure and an increased risk of serotonin syndrome

Interaction Summary

Coadministration of fluvoxaMINE with serotonergic drugs such as tricyclic antidepressants (TCAs) may elevate the plasma levels of TCAs and may increase the risk of serotonin syndrome. Caution is indicated with the coadministration of fluvoxaMINE and TCAs. Monitor plasma TCA concentrations and reduce the dose of TCA as needed. Also, monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and as the dosage increases. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of fluvoxaMINE and/or concomitant serotonergic drugs.

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of fluvoxaMINE with serotonergic drugs such as tricyclic antidepressants (TCAs) may elevate the plasma levels of TCAs and may increase the risk of serotonin syndrome. Caution is indicated with the coadministration of fluvoxaMINE and TCAs. Monitor plasma TCA concentrations and reduce the dose of TCA as needed. Also, monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and as the dosage increases. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, consider discontinuation of fluvoxaMINE and/or concomitant serotonergic drugs.

Mechanism Of Interaction

Additive serotonergic effects

Literature Reports

A) The effect of fluvoxaMINE on the pharmacokinetics of imipramine and desipramine were studied in 12 healthy volunteers. Imipramine half-life was significantly increased (from 23 to 41 hours) and clearance decreased (from 1.02 to 0.28 L/h/kg) when coadministered with fluvoxaMINE. No significant alterations in the pharmacokinetics of desipramine were found .

B) The addition of fluvoxaMINE to imipramine or desipramine in four patients was reported to result in greatly increased tricyclic antidepressant plasma levels. Three of the four patients showed signs of tricyclic toxicity .

C) The effect of fluvoxaMINE, 100 mg/day for 10 days, on plasma concentrations of tricyclic antidepressants was studied in 15 depressed patients on maintenance therapy with imipramine (7 patients) or desipramine (8 patients). A slight, but insignificant, increase in desipramine concentrations was found after 10 days, when fluvoxaMINE was added to desipramine therapy. Imipramine plasma levels were three to four times higher during fluvoxaMINE coadministration. One patient complained of anticholinergic effects, along with tremor and confusion. The mechanism of this drug interaction was inhibition of demethylation of imipramine .

D) FluvoxaMINE has been shown to significantly increase plasma levels of amitriptyline and clomiPRAMINE and to mildly increase levels of their metabolites nortriptyline and desmethylclomiPRAMINE, respectively. This may be due to competitive inhibition of oxidative metabolism in the liver .

E) Metabolism of tricyclic antidepressants coadministered with fluvoxaMINE was studied in eight depressed patients (one patient received amitriptyline). FluvoxaMINE was found to interfere with N-demethylation of amitriptyline. The combination of fluvoxaMINE and amitriptyline led to increased plasma levels of amitriptyline and decreased concentrations of amitriptyline's N-demethylated metabolite, nortriptyline. In addition, plasma levels of fluvoxaMINE were increased .

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.

Fluvoxamine Overview

• Fluvoxamine is used to treat obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over) and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). Fluvoxamine 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:

• 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.