Paroxetine with Clozapine Interaction Details

Brand Names Associated with Paroxetine

Brand Names Associated with Clozapine

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

Interaction Effect

Increased risk of anticholinergic toxicity, gastrointestinal adverse reactions, and QT prolongation

Interaction Summary

Concomitant use of clozapine (CYP2D6 substrate) with this drug (CYP2D6 inhibitor) may lead to increased clozapine levels and increased risk for adverse effects. Use caution and closely monitor during coadministration, consider clozapine dose reduction as necessary. When the inhibitor is discontinued monitor for lack of clozapine effectiveness and consider increasing the clozapine dose as necessary. Additionally, clozapine may result in CNS and peripheral anticholinergic toxicity, especially at higher doses. Treatment with clozapine and other drugs with anticholinergic activity (eg, this drug) may increase the risk for anticholinergic toxicity and severe gastrointestinal adverse reactions, ranging from constipation to paralytic ileus, related to hypomotility. Avoid concomitant use whenever possible. Clozapine may lead to QT prolongation, Torsade de pointes, and other life-threatening ventricular arrhythmias, cardiac arrest, or sudden cardiac death. Use caution when administering clozapine concomitantly with other medications that prolong the QT interval. Correct any electrolyte abnormalities. Discontinue clozapine if the QTc interval exceeds 500 msec. Cardiac evaluation and treatment discontinuation are warranted if the patient develops symptoms of torsade de pointes or other arrhythmias.

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant use of clozapine (CYP2D6 substrate) with this drug (CYP2D6 inhibitor) may lead to increased clozapine levels and increased risk for adverse effects. Use caution and closely monitor during coadministration, consider clozapine dose reduction as necessary. When the inhibitor is discontinued, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose as necessary. Additionally, clozapine may result in CNS and peripheral anticholinergic toxicity, especially at higher doses. Treatment with clozapine and other drugs with anticholinergic activity (eg, this drug) may increase the risk for anticholinergic toxicity and severe gastrointestinal adverse reactions, ranging from constipation to paralytic ileus, related to hypomotility. Avoid concomitant use whenever possible. Clozapine may lead to QT prolongation, Torsade de pointes, and other life-threatening ventricular arrhythmias, cardiac arrest, or sudden cardiac death. Use caution when administering clozapine concomitantly with other medications that prolong the QT interval. Correct any electrolyte abnormalities. Discontinue clozapine if the QTc interval exceeds 500 msec. Cardiac evaluation and treatment discontinuation are warranted if the patient develops symptoms of torsade de pointes or other arrhythmias.

Mechanism Of Interaction

Inhibition of CYP2D6-mediated metabolism of clozapine, additive anticholinergic effects and QT prolongation

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.

Clozapine Overview

• Clozapine is used to treat the symptoms of schizophrenia (a mental illness that causes disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions) in people who have not been helped by other medications or who have tried to kill themselves and are likely to try to kill or harm themselves again. Clozapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances 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.