Paroxetine with Atomoxetine Interaction Details

Brand Names Associated with Paroxetine

Brand Names Associated with Atomoxetine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Increased atomoxetine exposure

Interaction Summary

Concomitant use of PARoxetine (a CYP2D6 inhibitor) with atomoxetine (a CYP2D6 substrate) may increase the atomoxetine exposure. If coadministration is required, decrease the atomoxetine dosage as necessary[1]; conversely, an increase in the atomoxetine dosage may be needed with discontinuation of PARoxetine [2].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of PARoxetine (a CYP2D6 inhibitor) with atomoxetine (a CYP2D6 substrate) may increase the atomoxetine exposure. If coadministration is required, decrease the atomoxetine dosage as necessary[1]; conversely, an increase in the atomoxetine dosage may be needed with discontinuation of PARoxetine [2].

Mechanism Of Interaction

Inhibition of CYP2D6-mediated metabolism of atomoxetine

Literature Reports

A) In drug interactions studies, PARoxetine demonstrated the following effects on drugs metabolized by CYP2D6. PARoxetine 20 mg once daily at steady-state increased a single dose of desipramine 100 mg Cmax, AUC, and t(1/2) by approximately 2-, 5-, and 3-fold, respectively. In patients stabilized on risperiDONE 4 to 8 mg/day, daily PARoxetine 20 mg increased mean plasma concentrations of risperiDONE by 4-fold, decreased 9-hydroxyrisperiDONE concentrations by 10%, and increased concentrations of the active moiety by 1.4-fold. In healthy volunteers who were extensive CYP2D6 metabolizes, steady-sate atomoxetine AUC values were 6- to 8-fold higher and Cmax values were 3- to 4-fold higher with concomitant PARoxetine compared with atomoxetine alone. Mean digoxin steady-state AUC decreased by 15% in the presence of PARoxetine. In a study with propranolol 80 mg twice daily for 18 days, the steady-state plasma concentrations of propranolol were unaltered during coadministration with PARoxetine 30 mg once daily for the final 10 days [3].

B) PARoxetine significantly inhibited the metabolism of perphenazine in 8 healthy volunteers, resulting in increased plasma concentrations and side effects of perphenazine. All subjects were extensive metabolizers in CYP2D6 isoenzyme activity as determined by a dextromethorphan metabolism study. Subjects were randomized to receive a single dose of perphenazine 0.11 mg/kg or placebo alone in a crossover design. Then subjects received PARoxetine 20 mg/day for 10 days and then another dose of perphenazine or placebo on the tenth day. The average Cmax of perphenazine was significantly increased from 2.2 nanomol/L when given alone, compared to 13.5 nmol/L when given with PARoxetine. The average AUC (0 to 8 hours) was significantly increased from 9.4 mg x hr/L, with perphenazine alone, to 65.4 mg x hr/L when perphenazine was given with PARoxetine. Side effects of perphenazine were significantly increased as demonstrated by oversedation, extrapyramidal side effects, and impaired performance on psychomotor tests. In patients receiving PARoxetine the dose of perphenazine should be reduced and patients should be monitored for perphenazine side effects [4].

References

1 ) Product Information: BRISDELLE(R) oral capsules, paroxetine oral capsules. Sebela Pharmaceuticals Inc (per FDA), Roswell, GA, 2023.

2 ) Product Information: PAXIL(R) oral tablets, oral suspension, paroxetine oral tablets, oral suspension. Apotex Corp (per FDA), Weston, FL, 2023.

3 ) Product Information: PEXEVA(R) oral tablets, paroxetine mesylate oral tablets. Sebela Pharmaceuticals Inc (per FDA), Roswell, GA, 2023.

4 ) Ozdemir V, Naranjo CA, Herrman N, et al: Paroxetine potentiates the central nervous system side effects of perphenazine. Contribution of cytochrome P4502D6 inhibition in vivo. Clin Pharmacol Ther 1997; 62:334-347.

Paroxetine Overview

• Paroxetine tablets, suspension (liquid), and extended-release (long-acting) tablets are used to treat depression, panic disorder (sudden, unexpected attacks of extreme fear and worry about these attacks), and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). Paroxetine tablets and suspension are also used to treat obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), generalized anxiety disorder (GAD; excessive worrying that is difficult to control), and posttraumatic stress disorder (disturbing psychological symptoms that develop after a frightening experience). Paroxetine extended-release tablets are also used to treat premenstrual dysphoric disorder (PMDD, physical and psychological symptoms that occur before the onset of the menstrual period each month). Paroxetine capsules (Brisdelle) are used to treat hot flashes (sudden feelings of warmth, especially in the face, neck, and chest) in women who are experiencing menopause (stage of life when menstrual periods become less frequent and stop and women may experience other symptoms and body changes). Paroxetine is in a class of medications called selective serotonin-reuptake inhibitors (SSRIs). It treats depression and other mental illnesses by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance. There is not enough information available at this time to know how paroxetine works to treat hot flashes.

Atomoxetine Overview

• Atomoxetine is used as part of a total treatment program to increase the ability to pay attention and decrease impulsiveness and hyperactivity in children and adults with ADHD. Atomoxetine is in a class of medications called selective norepinephrine reuptake inhibitors. It works by increasing the levels of norepinephrine, a natural substance in the brain that is needed to control behavior.

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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.