Fluoxetine with Carbamazepine Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Carbamazepine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 25, 2023

Interaction Effect

Increased carBAMazepine exposure, an increased risk of carBAMazepine-related toxicity and an increased risk of serotonin syndrome

Interaction Summary

The concomitant use of carBAMazepine, a CYP3A4 substrate, and FLUoxetine, a CYP3A4 inhibitor, may increase the exposure of carBAMazepine and increase the risk of toxicity . Conversely, in 1 study of 8 patients no changes in steady state carBAMazepine levels have been reported with the addition of FLUoxetine . In a case report, symptoms of serotonin syndrome were reported with this combination . If carBAMazepine is used concomitantly with FLUoxetine, closely monitor for symptoms of serotonin syndrome  and carBAMazepine levels. Adjust the carBAMazepine dosage as needed .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of carBAMazepine, a CYP3A4 substrate, and FLUoxetine, a CYP3A4 inhibitor, may result in increased carBAMazepine exposure. If coadministering, closely monitor carBAMazepine levels and adjust the carBAMazepine dosage as needed. Exercise caution with coadministration of FLUoxetine and serotonergic agents, such as carBAMazepine, because it may result in a life-threatening condition called serotonin syndrome. If these agents are used together, discuss the risks of serotonin syndrome with the patient and monitor closely for symptoms of serotonin syndrome (mental status changes, autonomic instability, neuromuscular symptoms, seizures, and gastrointestinal symptoms), especially during treatment initiation and dose increases. If serotonin syndrome develops, discontinue FLUoxetine and any concomitant serotonergic agent and initiate supportive care .

Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of carBAMazepine by FLUoxetine; additive serotonergic effects

Literature Reports

A) An interaction between carBAMazepine and FLUoxetine was reported in 6 normal volunteers. CarBAMazepine was given for 28 days, and FLUoxetine was added to the regimen on day 7. The addition of FLUoxetine 20 mg daily to carBAMazepine 400 mg daily resulted in an increase in the AUC for both carBAMazepine and carBAMazepine-epoxide and a decrease in clearance of carBAMazepine. No significant changes were observed in absorption, volume of distribution, or elimination rate constant, indicating that FLUoxetine inhibits the metabolism of carBAMazepine .

B) The effect of FLUoxetine 20 mg daily was studied for 3 weeks in 8 epileptic patients who were stabilized on carBAMazepine therapy. Steady-state plasma levels of carBAMazepine and its epoxide metabolite were not significantly changed with concurrent use of FLUoxetine. These results differ from previous reports. The authors speculate that chronic carBAMazepine administration may have resulted in enzyme induction that caused decreased levels of FLUoxetine, thereby lowering the chances of a metabolic interaction. Unfortunately, FLUoxetine levels were not measured .

C) An interaction between carBAMazepine and FLUoxetine was reported in 2 patients receiving chronic carBAMazepine dosages of 600 mg and 1000 mg daily respectively. Within 7 to 10 days of initiation of FLUoxetine 20 mg daily, both patients developed symptoms of carBAMazepine toxicity. Symptoms disappeared within 2 weeks in one patient following carBAMazepine dosage reduction by 200 mg daily; in the other patient, FLUoxetine was discontinued with symptom resolution within 2 weeks .

D) Two cases of parkinsonism were reported after FLUoxetine was added to an existing carBAMazepine regimen. One patient, a 74-year old man, developed symptoms 3 days after FLUoxetine 20 mg per day was added to an existing 12-month regimen of carBAMazepine 200 mg twice daily. The patient developed cogwheel rigidity, a mask-like face, and a parkinsonian gait. After discontinuation of FLUoxetine and treatment with dexetimide, the patient showed only a slight hypertonia of the arms 17 days later. The other patient, a 53-year old woman, developed parkinsonian symptoms after FLUoxetine 20 mg per day was added to an existing regimen of carBAMazepine 200 mg twice daily. The patient had also been taking thioridazine 275 mg per day which was stopped when FLUoxetine was added. The patient developed cogwheel rigidity and a mask-like face 9 days after initiation of FLUoxetine therapy .

E) A female patient experienced a drug interaction 14 days after she had FLUoxetine 20 mg added to a regimen of carBAMazepine 200 mg daily. The patient presented with symptoms of serotonin syndrome, such as uncontrollable shivering, agitation, incoordination, myoclonus, hyperreflexia, and diaphoresis. The patient also had leukopenia and thrombocytopenia. After discontinuation of FLUoxetine, all symptoms of serotonin syndrome and hematological abnormalities resolved over the next 72 hours .

F) Patients on stable doses of carBAMazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant FLUoxetine treatment .

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.

Carbamazepine Overview

• Carbamazepine is used alone or in combination with other medications to control certain types of seizures in people with epilepsy. It is also used to treat trigeminal neuralgia (a condition that causes facial nerve pain). Carbamazepine extended-release capsules (Equetro brand only) are also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen at the same time) in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in the brain.

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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.