Fluoxetine with Diazepam Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Diazepam

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 19, 2023

Interaction Effect

Increased diazePAM exposure

Interaction Summary

During coadministration of FLUoxetine with diazePAM, the FLUoxetine area under the concentration-time curve (AUC) was increased, but this was not associated with increased impairment. Conversely, a controlled study observed significant decreases in psychomotor performance when diazePAM was added to FLUoxetine . The metabolism of diazePAM is mediated by several P450 enzymes which may be inhibited by FLUoxetine . Concurrent administration of FLUoxetine with diazePAM may prolong the half-life of diazePAM in some patients .

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concurrent administration of FLUoxetine with diazePAM may prolong the half-life of diazePAM in some patients.

Mechanism Of Interaction

Inhibition of the hepatic P450 metabolism of diazePAM

Literature Reports

A) Coadministration of FLUoxetine and diazePAM resulted in prolonged half-life, reduced plasma clearance, and increased AUC for diazePAM. Oral diazePAM 10 mg was given alone, after a single dose of oral FLUoxetine 60 mg, and after 8 daily doses of FLUoxetine 60 mg. Psychometric data demonstrated no effect of FLUoxetine on the psychomotor response to diazePAM. Thus, although FLUoxetine decreases the clearance of diazePAM, this does not appear to be of clinical relevance and dosing adjustments are not required during combined therapy .

B) Combined therapy with diazePAM and FLUoxetine caused an increase in the half-life of the metabolite desmethyldiazePAM, but this did not appear to be clinically significant. diazePAM had no effect on the disposition of FLUoxetine or norFLUoxetine .

C) To date, in-vitro studies have found that diazePAM demethylation occurs via P450 1A2, 3A4, 2C9, and 2C19. Evidence with drugs known to be metabolized by these enzymes suggests that FLUoxetine strongly inhibits 2C9, moderately inhibits 2C19 and 3A4, and has no effect on 1A2 .

D) In a controlled study of performance of 90 healthy volunteers, the effects of FLUoxetine, amitriptyline, or placebo with diazePAM were studied. Volunteers received one of six treatment combinations, and were given performance tests including a critical tracking test, divided attention test, visual search task, memory test, and vigilance test. FLUoxetine alone did not affect performance, but when FLUoxetine was added to diazePAM, there was a significant increase in the divided attention tracking error and significant impairment on the vigilance test. For amitriptyline alone and during coadministration with diazePAM, significant impairment was observed. On most tests, the combination of amitriptyline and diazePAM resulted in additive effects. The authors concluded that the combination of diazePAM and an antidepressant may increase an individual's risk during driving and while performing other complex tasks .

E) A case was reported in which an 83-year old man developed delirium after the addition of FLUoxetine and diazePAM to a regimen of warfarin, lisinopril, furosemide, potassium, digoxin, and acetaminophen. The patient was given FLUoxetine 20 mg per day and diazePAM 2.5 mg three to four times per day for symptoms of depression, anxiety, and insomnia. The patient then developed symptoms of drug delirium, including confusion, incoherence, and irrational speaking. The patient also developed an increased international normalized ratio (INR), after which FLUoxetine was discontinued. The patient presented to the hospital with left-sided weakness and later died from complications of a large interparenchymal hemorrhage. The authors proposed that the addition of FLUoxetine to the patient's regimen resulted in increased serum levels of both warfarin and diazePAM, resulting in drug-induced delirium and loss of anticoagulant control .

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.

Diazepam Overview

• Diazepam is used to relieve anxiety and to control agitation caused by alcohol withdrawal. It is also used along with other medications to control muscle spasms and spasticity caused by certain neurological disorders such as cerebral palsy (condition that causes difficulty with movement and balance), paraplegia (inability to move parts of the body), athetosis (abnormal muscle contractions), and stiff-man syndrome (a rare disorder with muscle rigidity and stiffness). Diazepam is also used along with other medications to control seizures. Diazepam is in a class of medications called benzodiazepines. It works by calming abnormal overactivity 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.