Paroxetine with Paliperidone Interaction Details

Brand Names Associated with Paroxetine

Brand Names Associated with Paliperidone

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

Interaction Effect

Increased paliperidone exposure and an increased risk of QT interval prolongation

Interaction Summary

Concurrent use of paliperidone and PARoxetine may result in increased paliperidone plasma concentrations. Paliperidone (9-hydroxyrisperiDONE) is the major active metabolite of risperiDONE. Concomitant use of PARoxetine and risperiDONE has resulted in increased plasma concentrations of both risperiDONE and 9-hydroxyrisperiDONE, particularly at higher (40 mg) PARoxetine doses . PARoxetine is associated with ventricular tachycardia and torsade de pointes. Hence, coadministration of PARoxetine with other QT prolonging drugs such as paliperidone may increase the risk of QT interval prolongation .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Use caution when paliperidone and PARoxetine are used concomitantly as this may result in increased paliperidone plasma concentrations. PARoxetine is associated with ventricular tachycardia and torsade de pointes. Hence, coadministration of PARoxetine with other QT prolonging drugs such as paliperidone may increase the risk of QT interval prolongation .

Mechanism Of Interaction

Inhibition of the CYP2D6-mediated metabolism of paliperidone; additive QT interval prolongation

Literature Reports

A) In a drug interaction study, paliperidone exposures were a significant 16% (90% confidence interval, 4% to 30%) higher on average in CYP2D6 extensive metabolizers who were treated concomitantly with a single dose of paliperidone 3 mg and PARoxetine 20 mg/day. Studies with higher PARoxetine doses have not been conducted. The clinical relevance is not known .

B) PARoxetine, a potent inhibitor of cytochrome CYP2D6, may impair the elimination of risperiDONE, primarily by inhibiting CYP2D6-mediated alpha-hydroxylation and, to a lesser extent, by simultaneously affecting the further metabolism of 9-hydroxyrisperiDONE (9-OH-risperiDONE) or other pathways of risperiDONE biotransformation. In a study including 10 patients diagnosed with schizophrenia (n=7) or schizoaffective disorder depressive type (n=3), risperiDONE plasma concentrations increased when PARoxetine was coadministered with risperiDONE. Patients were stabilized on risperiDONE therapy 4 to 8 mg/day and received adjunctive PARoxetine 20 mg/day to treat negative symptoms, concomitant depression, or both. RisperiDONE dosage remained constant throughout the duration of the study. A significant elevation in risperiDONE plasma concentrations (p less than 0.01) and a slight, nonsignificant decrease in 9-OH-risperiDONE occurred. After 4 weeks of PARoxetine treatment, the total concentration of risperiDONE and 9-OH-risperiDONE was increased by 45% (p less than 0.05). The mean plasma risperiDONE to 9-OH-risperiDONE ratio also changed significantly (p less than 0.001) with concomitant PARoxetine treatment. Extrapyramidal side effects occurred in one patient during the second week of PARoxetine coadministration. Total plasma levels of risperiDONE in this patient increased 62% over baseline values during PARoxetine coadministration. The occurrence of extrapyramidal symptoms in patients after addition of SSRIs to antipsychotics might also be caused by an additive pharmacodynamic effect of PARoxetine .

C) RisperiDONE plasma concentrations increased when risperiDONE-treated inpatients (n=12) with schizophrenia and negative symptoms were coadministered incremental doses of PARoxetine. Prior to initiating PARoxetine, patients were receiving risperiDONE 2 mg twice daily for at least 6 weeks and steady-state plasma concentrations of risperiDONE and 9-hydroxyrisperiDONE (9-OH-risperiDONE) had been achieved. PARoxetine doses were administered in 3 consecutive 4-week increments of 10 mg/day, 20 mg/day, and 40 mg/day. Mean risperiDONE plasma concentrations during 10-, 20-, and 40-mg PARoxetine treatment were 3.8- (95% confidence interval (CI), 3.2 to 5.8; p less than 0.01) , 7.1- (95% CI, 5.3 to 16.5; p less than 0.01), and 9.7-fold (95% CI, 7.8 to 22.5; p less than 0.01) higher compared with baseline. Increases in 9-OH-risperiDONE concentrations were not significant with PARoxetine use. Mean active moiety (risperiDONE plus 9-OH-risperiDONE) plasma concentrations increased by 1.8-fold (95% CI, 1.4 to 2.7; p less than 0.05) during the 40-mg PARoxetine dose; increases were not significant with 10- or 20-mg doses. Metabolic ratio was significantly increased (p less than 0.01) by 4.2-fold (95% CI, 3.4 to 6.2) with 10 mg of PARoxetine, by 8.2-fold (95% CI, 6 to 16) with 20 mg, and by 12.6-fold (95% CI, 9.6 to 26.8) with 40 mg. Negative symptom scores were significantly improved during all PARoxetine doses; however, extrapyramidal symptoms scores were significantly higher during 20- and 40-mg doses. The authors suggest that low-dose coadministration of paroxetine with risperiDONE may be safe and effective for treating schizophrenia with negative symptoms .

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.

Paliperidone Overview

• Paliperidone 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). Paliperidone 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.