Fluoxetine with Alprazolam Interaction Details

Brand Names Associated with Fluoxetine

Brand Names Associated with Alprazolam

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 27, 2024

Interaction Effect

An increased risk of ALPRAZolam toxicity (somnolence, dizziness, ataxia, slurred speech, hypotension, psychomotor impairment)

Interaction Summary

Coadministered FLUoxetine increases ALPRAZolam serum concentrations[1][2] and in further psychomotor performance decrement due to increased ALPRAZolam levels [3].

Severity

Moderate

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Coadministration of ALPRAZolam and FLUoxetine has resulted in increased ALPRAZolam plasma concentrations and in further psychomotor performance decrement due to increased ALPRAZolam levels[3].

Mechanism Of Interaction

Inhibition of CYP3A-mediated ALPRAZolam metabolism

Literature Reports

A) ALPRAZolam serum concentrations were analyzed in a double-blind, placebo-controlled study involving 80 healthy male volunteers [2]. Concurrent administration of ALPRAZolam 1 mg four times a day and FLUoxetine 60 mg each morning for four days resulted in a 30% increase in plasma ALPRAZolam levels and a 21% decrease in the ALPRAZolam elimination rate. The elevated ALPRAZolam concentrations caused increased psychomotor impairment, but did not affect mood status or sedation.

B) The effect of FLUoxetine on the pharmacokinetics of ALPRAZolam was analyzed in a 31-day, double-blind, crossover, placebo-controlled study, which included a 10-day washout period [1]. Twelve healthy male volunteers were given FLUoxetine 20 mg twice a day or placebo and a single dose of ALPRAZolam 1 mg on days 3 and 24. FLUoxetine significantly increased the half-life of ALPRAZolam from 17 hours to 20 hours and significantly decreased its clearance from 61 mL/min to 48 mL/min.

C) Inhibition of ALPRAZolam metabolism by FLUoxetine occurs via cytochrome P450 3A4. A randomized, double-blind, placebo-controlled with-in subject design was used to assess this potential interaction. Twenty healthy volunteers attended four study sessions: ALPRAZolam/placebo was given in the absence of an SSRI in the first two study sessions; ALPRAZolam/placebo while at steady-state with either citalopram 20 mg/day or FLUoxetine 20 mg/day was given in the last two study sessions. At each session they received ALPRAZolam 1 mg orally or placebo. FLUoxetine significantly prolonged the half-life of ALPRAZolam by 16% and increased the area under the concentration-time curve by 32%. Citalopram did not affect these parameters. The effects of ALPRAZolam were not altered by either SSRI. These findings suggest that citalopram and FLUoxetine differentially alter ALPRAZolam concentrations [4].

References

1 ) Greenblatt DJ, Preskorn SH, Cotreau MM, et al: Fluoxetine impairs clearance of alprazolam but not of clonazepam. Clin Pharmacol Ther 1992; 52:479-486.

2 ) Lasher TA, Fleishaker JC, Steenwyk RC, et al: Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine. Psycopharmacology 1991; 104:323-327.

3 ) Product Information: PROZAC(R) oral capsules, fluoxetine oral capsules. Lilly USA LLC (per FDA), Indianapolis, IN, 2023.

4 ) Hall J, Naranjo C, Sproule B, et al: Citalopram and fluoxetine differentially alter alprazolam concentrations (abstract TPII-43). Clin Pharmacol Ther 2002; 71(2):P52.

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.

Alprazolam Overview

• Alprazolam is used to treat anxiety disorders and panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks). Alprazolam is in a class of medications called benzodiazepines. It works by decreasing abnormal excitement 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.