Mitotane with Risperidone Interaction Details

Brand Names Associated with Mitotane

Brand Names Associated with Risperidone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 29, 2023

Interaction Effect

Reduced risperiDONE exposure, reduced 9-hydroxyrisperiDONE exposure and reduced efficacy of risperiDONE

Interaction Summary

Coadministration a CYP3A4 inducer and risperiDONE may lead to reduced risperiDONE and 9-hydroxyrisperiDONE (active metabolite) combined exposure. If a CYP3A4 inducer is initiated, closely monitor during the first 4 to 8 weeks. In patients receiving PERSERIS(TM) 90 mg, consider increasing the dose to 120 mg. In patients receiving UZEDY(TM) at a specific dose, consider increasing to the next highest dose. In patients receiving PERSERIS(TM) 120 mg or UZEDY(TM) 125 mg once monthly or 250 mg once every 2 months, additional oral risperiDONE may be necessary. Upon discontinuation of the CYP3A4 inducer, re-evaluate risperiDONE dosage and decrease as necessary. 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. For risperiDONE IM, decrease dose 2 to 4 weeks before the discontinuation of this drug. If patients are receiving risperiDONE 25 mg IM, treatment may be continued unless the clinician deems it necessary to interrupt or to lower the risperiDONE dosage; a risperiDONE 12.5 mg IM dose may be considered, but efficacy has not been established .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of a CYP3A4 inducer and risperiDONE may lead to reduced risperiDONE and 9-hydroxyrisperiDONE (active metabolite) combined exposure. If a CYP3A4 inducer is initiated, closely monitor during the first 4 to 8 weeks. In patients receiving PERSERIS(TM) 90 mg, consider increasing the dose to 120 mg. In patients receiving UZEDY(TM) at a specific dose, consider increasing to the next highest dose. In patients receiving PERSERIS(TM) 120 mg or UZEDY(TM) 125 mg once monthly or 250 mg once every 2 months, additional oral risperiDONE may be necessary. Upon discontinuation of the CYP3A4 inducer, re-evaluate risperiDONE dosage and decrease as necessary. 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. For risperiDONE IM, decrease dose 2 to 4 weeks before the discontinuation of this drug. If patients are receiving risperiDONE 25 mg IM, treatment may be continued unless the clinician deems it necessary to interrupt or to lower the risperiDONE dosage; a risperiDONE 12.5 mg IM dose may be considered, but efficacy has not been established .

Mechanism Of Interaction

Induction of CYP3A4-mediated metabolism of risperiDONE

Literature Reports

A) In an drug interaction study, carBAMazepine induced the metabolism of risperiDONE in a 22-year-old male patient with chronic schizophrenia, resulting in low risperiDONE levels and lack of effectiveness. The patient was started on carBAMazepine 600 mg daily and risperiDONE 4 mg daily. The plasma concentration of 9-hydroxyrisperiDONE was less than half the expected concentration when the dose of risperiDONE was doubled to 8 mg daily. After achieving a therapeutic plasma concentration of 9-hydroxyrisperiDONE (19 mcg/L), the dose of carBAMazepine was tapered and stopped. Plasma levels of 9-hydroxyrisperiDONE increased to 49 mcg/L, necessitating a decrease in the dose of risperiDONE .

B) Plasma concentrations of risperiDONE and 9-hydroxyrisperiDONE decreased when carBAMazepine was added or increased when it was discontinued in a pharmacokinetic study in 34 patients with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder. All patients were stabilized on risperiDONE alone or in combination with carbamazepine for at least 4 weeks. Steady-state plasma concentrations of risperiDONE and 9-hydroxyrisperiDONE were compared in patients treated with risperiDONE alone and patients comedicated with carbamazepine. The plasma concentrations of both 9-hydroxyrisperiDONE and the sum of risperiDONE and 9-hydroxyrisperiDONE (active moiety) differed significantly among groups. In five patients evaluated with and without comedication, the plasma concentrations of risperiDONE and 9-hydroxyrisperiDONE decreased when carbamazepine was added or increased when it was discontinued. The results demonstrate that in patients receiving risperiDONE alone, the concentration of the active moiety (risperiDONE plus its active metabolite 9-hydroxyrisperiDONE) was reduced by approximately 70% when carbamazepine was given concomitantly .

C) The concomitant use of carBAMazepine and risperiDONE lead to a marked decrease in the steady-state plasma concentrations of risperiDONE and 9-hydroxyrisperiDONE through stimulation of an inducible cytochrome as well as the influence of the cytochrome P450 2D6 genotype. A 50-year-old man with chronic schizophrenia and deficient CYP2D6 activity was given carBAMazepine with his existing risperiDONE therapy. carBAMazepine 800 mg/day for 5 days was added to his medication regimens as a mood stabilizer. After 4 weeks of carBAMazepine treatment, the patient exhibited psychotic symptoms including hallucinations, paranoid delusions, ideas of reference, and mild excitement. Plasma concentrations of risperiDONE and its active metabolite 9-hydroxyrisperiDONE, had decreased from 22 and 30 ng/mL, respectively. carBAMazepine concentration was 8.2 mcg/mL. The risperiDONE dose was increased to 9 mg/day, carBAMazepine was discontinued, and lorazepam 5 mg/day was added. Psychotic symptoms improved over the following 3 weeks and concentrations of risperiDONE and 9-hydroxyrisperiDONE increased to 40 and 57 ng/mL, respectively. A resultant decrease in the plasma concentrations of risperiDONE and 9-hydroxyrisperiDONE suggest that the CYP2D6 genotype may influence susceptibility to a clinically important interaction with risperiDONE and carBAMazepine .

D) Eleven patients with schizophrenia in a drug interaction study received oral risperiDONE titrated to 6 mg/day for 3 weeks, followed by concurrent administration of carBAMazepine for an additional 3 weeks. The plasma concentrations of risperiDONE and its pharmacologically active metabolite, 9-hydroxyrisperiDONE, were decreased by about 50% .

E) In a drug interaction study, carBAMazepine coadministered with oral risperiDONE decreased the steady-state plasma concentrations of risperiDONE and 9-hydroxyrisperiDONE by about 50%. Plasma concentrations of carBAMazepine did not appear to be affected. Coadministration of other known CYP3A4 enzyme inducers (e.g., phenytoin, rifAMPin, and PHENobarbital) with risperiDONE may cause similar decreases in the combined plasma concentrations of risperidone and 9-hydroxyrisperiDONE, which could lead to decreased efficacy of risperiDONE .

Mitotane Overview

• Mitotane is used to treat cancer of the adrenal gland that can not be treated with surgery. Mitotane is in a class of medications called antineoplastic agents. It works by slowing growth or reducing the size of the tumor.

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.

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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.