Paroxetine with Cimetidine Interaction Details

Brand Names Associated with Paroxetine

Brand Names Associated with Cimetidine

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

Interaction Effect

Increased PARoxetine exposure and possibly PARoxetine toxicity (dizziness, somnolence, nausea, headache)

Interaction Summary

Coadministered cimetidine may increase serum concentrations of PARoxetine by as much as 50% to 80% in some patients. The clinical significance of this interaction is unclear. In one study, no adverse clinical effects were reported. In another study, tiredness, dizziness, headache, muscle tension, and GI distress were observed; these effects were also reported with PARoxetine alone, but to a lesser extent. The mechanism of this interaction is thought to be inhibition by cimetidine of P450 isoenzymes responsible for PARoxetine metabolism. Also since cimetidine is known to inhibit the CYP2D6 isoenzyme, cimetidine and PARoxetine coadministration could result in increased PARoxetine plasma concentrations, and possibly PARoxetine toxicity. Monitor clinical effect of PARoxetine .

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Monitor clinical effect of PARoxetine. Since cimetidine is known to inhibit the CYP2D6 isoenzyme, cimetidine and PARoxetine coadministration could result in increased PARoxetine plasma concentrations, and possibly PARoxetine toxicity.

Mechanism Of Interaction

Inhibition of CYP2D6-mediated PARoxetine metabolism; inhibition of CYP450-mediated PARoxetine metabolism

Literature Reports

A) In a multiple-dose study in 11 healthy volunteers, concurrent administration of oral cimetidine and PARoxetine resulted in a mean increase of 51% in the area under the concentration-time curve (AUC) for PARoxetine. Maximum concentration (Cmax) of PARoxetine increased by 45%. Volunteers received PARoxetine 30 mg once a day for 28 days, with cimetidine 300 mg three times daily given during the last 7 days. No changes in half-life or elimination rate constant occurred. The increases in the PARoxetine AUC and maximum concentration were attributed to inhibition of first-pass metabolism of PARoxetine by cimetidine. No adverse clinical effects were observed during the study .

B) Effects of cimetidine on a single dose of PARoxetine were studied in 10 healthy male subjects . Subjects received 8 days of cimetidine 200 mg four times daily followed by a 30 mg dose of PARoxetine. Pharmacokinetic values were compared with those of the same dose of PARoxetine given before initiation of the H-2 blocker. The mean AUC of PARoxetine increased from 195.98 to 308.36 ng-h/mL (a 57% increase), but, due to high interindividual variation, this increase did not attain statistical significance. In two subjects, the increases were 55% and 81%, respectively.

C) Cimetidine inhibits many cytochrome P450 enzymes. In a study in which PARoxetine (30 mg once daily) was dosed orally for 4 weeks, steady-state plasma concentrations of PARoxetine were increased by approximately 50% during coadministration with oral cimetidine (300 mg three times daily) for the final week

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.

Cimetidine Overview

• Cimetidine is used to treat ulcers; gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus); and conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome. Over-the-counter cimetidine is used to prevent and treat symptoms of heartburn associated with acid indigestion and sour stomach. Cimetidine is in a class of medications called H₂ blockers. It decreases the amount of acid made in the stomach.

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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.