Risperidone with Bupropion Interaction Details

Brand Names Associated with Risperidone

Brand Names Associated with Bupropion

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 06, 2024

Interaction Effect

Increased risperiDONE exposure and reduced 9-hydroxyrisperiDONE exposure

Interaction Summary

Concomitant use of risperidone (a CYP2D6 substrate) and a strong CYP2D6 inhibitor may result in increased risperiDONE exposure and decreased exposure of the major active metabolite 9-hydroxyrisperiDONE. If initiating a strong CYP2D6 inhibitor, patients should be placed on the lowest dose of PERSERIS(TM) 90 mg or UZEDY(TM) 50 mg once monthly or 100 mg once every 2 months between 2 to 4 weeks prior to the planned start of the strong CYP2D6 inhibitor. If the patient is already receiving PERSERIS(TM) 90 mg or UZEDY(TM) 50 mg once monthly or 100 mg once every 2 months, continue treatment at the current dose unless clinical judgement necessitates interruption[1][2]. Consider a initial dosage of risperiDONE 12.5 mg IM in patients already receiving a strong CYP2D6 inhibitor. If initiating a strong CYP2D6 inhibitor, reduce risperiDONE dosage 2 to 4 weeks before a planned initiation of strong inhibitor and adjust dosage to desired effect. When initiating a strong inhibitor in patients already receiving risperiDONE 25 mg IM, continue treatment with the 25 mg dose unless clinical judgment requires lowering the dose to 12.5 mg or necessitates interruption The efficacy of risperiDONE 12.5 mg dose has not been established [3].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of risperidone (a CYP2D6 substrate) and a strong CYP2D6 inhibitor may result in increased risperiDONE exposure and decreased exposure of the major active metabolite 9-hydroxyrisperiDONE. If initiating a strong CYP2D6 inhibitor, patients should be placed on the lowest dose of PERSERIS(TM) 90 mg or UZEDY(TM) 50 mg once monthly or 100 mg once every 2 months between 2 to 4 weeks prior to the planned start of the strong CYP2D6 inhibitor. If the patient is already receiving PERSERIS(TM) 90 mg or UZEDY(TM) 50 mg once monthly or 100 mg once every 2 months, continue treatment at the current dose unless clinical judgement necessitates interruption[1][2]. Consider a initial dosage of risperiDONE 12.5 mg IM in patients already receiving a strong CYP2D6 inhibitor. If initiating a strong CYP2D6 inhibitor, reduce risperiDONE IM dosage 2 to 4 weeks before a planned initiation of strong inhibitor and adjust dosage to desired effect. When initiating a strong inhibitor in patients already receiving risperiDONE 25 mg IM, continue treatment with the 25 mg dose unless clinical judgment requires lowering the dose to 12.5 mg or necessitates interruption The efficacy of risperiDONE 12.5 mg dose has not been established [3].

Mechanism Of Interaction

Inhibition of CYP2D6-mediated metabolism of risperiDONE

Literature Reports

A) Approximately 3 to 9-fold increases in mean plasma concentrations of risperiDONE occurred with coadministration of paroxetine, a strong CYP2D6 inhibitor at a dosage of 20 mg/day. Paroxetine lowered the concentration of 9-hydroxyrisperiDONE by about 10% [3][2].

B) FLUoxetine (a strong CYP2D6 inhibitor) 20 mg/day has been shown to increase the plasma concentration of risperiDONE (a CYP2D6 substrate) 2.5- to 2.8-fold. FLUoxetine did not affect the concentration of 9-hydroxyrisperiDONE. The dosage of risperiDONE should be re-evaluated when FLUoxetine is initiated or discontinued [3][2].

C) In a 4-week, pharmacokinetic study including 9 patients with schizophrenia or schizoaffective disorder, coadministration with FLUoxetine resulted in an risperiDONE active moiety (risperiDONE plus 9-hydroxyrisperiDONE) concentration increase by 75% (range: 9% to 204%) compared with baseline. Patients were stabilized on a fixed dose of risperiDONE 4 to 6 mg/day for at least 4 weeks and received adjunctive FLUoxetine therapy 20 mg/day for the management of concomitant depression. Mean plasma risperiDONE concentrations increased from 12 nanograms (ng)/mL (ng/mL; 29 nanomol/L) at baseline to 49 ng/mL (119 nanomol/L) at week 2, and 56 ng/mL (136 nanomol/L) at week 4. 9-hydroxyrisperiDONE plasma concentrations showed no significant increase at 4 weeks. The mean plasma risperiDONE to 9-hydroxyrisperiDONE ratio also increased significantly. Two patients experienced parkinsonian symptoms during week 2 of concomitant therapy requiring anticholinergic medication. The authors suggest that monitoring plasma risperiDONE levels may be warranted in patients receiving concomitant FLUoxetine and risperiDONE treatment [4].

References

1 ) Product Information: PERSERIS(TM) subcutaneous extended-release injectable suspension, risperidone subcutaneous extended-release injectable suspension. Indivior Inc (per manufacturer), North Chesterfield, VA, 2018.

2 ) Product Information: UZEDY(TM) subcutaneous extended-release suspension, risperidone subcutaneous extended-release suspension. Teva Pharmaceuticals (per FDA), Parsippany, NJ, 2023.

3 ) Product Information: RYKINDO(R) intramuscular extended-release injection, risperidone intramuscular extended-release injection. Luye Pharma (USA) Ltd (per FDA), Princeton, NJ, 2023.

4 ) Spina E, Avenoso A, Scordo M, et al: Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia: a clinically relevant pharmacokinetic drug interaction. J Clin Psychopharmacol 2002; 22(4):419-423.

Risperidone Overview

• Risperidone 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 adults and teenagers 13 years of age and older. It is also used to treat episodes of mania (frenzied, abnormally excited, or irritated mood) or mixed episodes (symptoms of mania and depression that happen together) in adults and in teenagers and children 10 years of age and older with bipolar disorder (manic depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Risperidone is also used to treat behavior problems such as aggression, self-injury, and sudden mood changes in teenagers and children 5 to 16 years of age who have autism (a condition that causes repetitive behavior, difficulty interacting with others, and problems with communication). Risperidone is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.

Bupropion Overview

• Bupropion (Aplenzin, Wellbutrin, Wellbutrin SR, Wellbutrin XL) is used to treat depression. Bupropion (Aplenzin, Wellbutrin XL) is also used to treat seasonal affective disorder (SAD; episodes of depression that occur at the same time each year [usually in the fall and winter but rarely may occur in the spring or summer months]). Bupropion (Zyban) is used to help people stop smoking. Bupropion is in a class of medications called antidepressants. It works by increasing certain types of activity 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.