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  • CLASSES

    Serotonin-Dopamine Antagonist (SDA) Antipsychotics

    BOXED WARNING

    Dementia, geriatric

    Reported clinical experience has not identified differences in responses between elderly and younger patients receiving oral or injectable risperidone. In general, a lower starting dose is recommended for the geriatric patient, reflecting a decreased drug clearance in the elderly. Orthostatic risk in the elderly may be minimized using a lower initial dose of risperidone followed by careful titration. Monitor blood pressure and renal function. Antipsychotics, including risperidone, are not approved for the treatment of dementia-related psychosis in geriatric patients. All atypical antipsychotic labels include a boxed warning regarding increased morbidity and mortality (1.6 to 1.7 times vs. placebo) reported in geriatric patients with dementia receiving atypical antipsychotics. Deaths typically occurred due to heart failure, sudden death, or infections (primarily pneumonia). An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has been reported. Geriatric patients may also be at increased risk for developing a prolonged QT interval when using risperidone. According to the Beers Criteria, antipsychotics are considered potentially inappropriate medications (PIMs) in elderly patients, and use should be avoided except for treating schizophrenia or bipolar disorder, and for short-term use as antiemetics during chemotherapy. Avoid use of risperidone in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: delirium (possible new-onset or worsening delirium), dementia (adverse CNS effects), and Parkinson's disease (symptom exacerbation). There is an increased risk of stroke and a greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics. The Beers expert panel recommends avoiding antipsychotics to treat delirium- or dementia-related behavioral problems unless non-pharmacological options have failed or are not possible and the patient is a substantial threat to self or others. Avoid antipsychotics in elderly patients with a history of falls or fractures unless safer alternatives are not available since antipsychotics can cause ataxia, impaired psychomotor function, syncope, and new falls. If use is necessary, consider reducing the use of other CNS-active medications and implement other strategies to reduce fall risk. Because antipsychotics can cause or exacerbate hyponatremia and SIADH, particularly in the elderly, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). An antipsychotic should generally be used only for the conditions listed in the guidelines (e.g., schizophrenia, mood disorder, Tourette's disorder) and meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. The LTCF must identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic, as there is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. To initiate antipsychotic therapy, the patient must either be a danger to self or others or have symptoms due to mania or psychosis, and the plan of care should document attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less and evaluate/document within 7 days the contributors/causes to the symptoms. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. Treatment of non-acute, chronic, or prolonged BPSD must meet all of the OBRA criteria for BPSD treatment and ensure that the behavioral symptoms are not due to a treatable medical condition or correctable environmental or psychological stressors alone and the facility must provide documented evidence of persistence. The LTCF must evaluate the appropriateness of antipsychotic treatment during or within 2 weeks of admission for a newly admitted resident. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. In all cases, the lowest possible dose and the shortest duration should be prescribed and the facility should monitor for ongoing effectiveness and potential adverse effects. Antipsychotics are subject to periodic review for effectiveness, medical necessity/rationale for use, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and parenteral atypical antipsychotic of the benzisoxazole class
    Used orally and as an extended-release (ER) intramuscular injection in adults for schizophrenia and bipolar I disorder; a subcutaneous ER injection is used for schizophrenia in adults; in selected pediatric patients used orally for schizophrenia, bipolar I disorder, and irritability associated with autistic disorder
    As with all antipsychotics, boxed warning for increased mortality risk in elderly patients with dementia-related psychosis

    COMMON BRAND NAMES

    PERSERIS, Risperdal, Risperdal Consta, Risperdal M-Tab

    HOW SUPPLIED

    PERSERIS Subcutaneous Inj Susp ER: 90mg, 120mg
    Risperdal Consta Intramuscular Inj Pwd F/Sol: 12.5mg, 25mg, 37.5mg, 50mg
    Risperdal M-Tab/Risperidone Oral Tab Orally Dis: 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg
    Risperdal/Risperidone Oral Sol: 1mg, 1mL
    Risperdal/Risperidone Oral Tab: 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg

    DOSAGE & INDICATIONS

    For the treatment of schizophrenia.
    Oral dosage
    Adults

    To minimize the risk for orthostatic hypotension and syncope, initiate at 2 mg/day PO given as a single dose or as 1 mg PO twice per day. Adjust dose at intervals of at least 24 hours and in increments of 1 mg/day to 2 mg/day as tolerated to the recommended target dose of 4 mg/day to 8 mg/day PO. Effective range: 4 mg/day to 16 mg/day PO. The total daily dose of risperidone may be administered once daily or in 2 divided doses. During clinical trial evaluation, doses above 6 mg/day PO were not more effective than lower doses and they were associated with more extrapyramidal symptoms and other adverse effects. In one study, the efficacy results for 8 mg/day were generally greater than for 4 mg/day. Patient response to antipsychotics is variable. Individualize dosage. Use the lowest effective dose. Max: 16 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. A dose reduction should be considered if hypotension occurs. Maintenance treatment is typically recommended for patients who have responded to initial treatment. Periodically re-assess the need for continued treatment. In one controlled trial, doses of 2 mg/day to 8 mg/day effectively delayed relapse in adult patients who had been clinically stable for at least 4 weeks and were then followed for 1 to 2 years. RE-INITIATION OF TREATMENT: The initial dose titration should be followed in patients who have previously discontinued the drug.

    Geriatric Adults

    To minimize the risk of orthostatic hypotension and syncope, initiate with 0.5 mg PO twice per day followed by careful titration. The usual adult titration schedule includes dose adjustments at intervals of at least 24 hours and in increments of 1 mg/day to 2 mg/day as tolerated to the recommended target dose range of 4 mg/day to 8 mg/day PO. Slower titration may be needed in geriatrics due to the potential for impaired renal function. Effective dose range: 4 mg/day to 16 mg/day PO. May give the total daily dose once daily or in 2 divided doses. During clinical trial evaluation, doses above 6 mg/day were not more effective than lower doses and were associated with more extrapyramidal symptoms and other adverse effects. Individualize dosage. Use the lowest effective dose. Max: 16 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. A dose reduction should be considered if hypotension occurs. Maintenance treatment is typically recommended for patients who have responded to initial treatment. Periodically re-assess the need for continued treatment. RE-INITIATION OF TREATMENT: The initial dose titration should be followed in patients who have previously discontinued the drug.

    Adolescents

    0.5 mg PO once daily initially. May administer in divided doses to increase tolerability. Adjust dose at intervals of at least 24 hours and in increments of 0.5 to 1 mg/day as tolerated to the recommended target dose of 3 mg/day. The effective dose range is 1 to 6 mg/day PO; however, doses above 3 mg/day do not appear to provide additional therapeutic benefits and may result in more adverse events. Max: 6 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Responding patients generally continue treatment beyond the acute episode. Periodically reassess safety and efficacy during chronic use.

    Children† 8 to 12 years

    Dosage not established; not FDA-approved. Literature suggests 0.5 mg/day PO initially. May give in divided doses to increase tolerability. Follow with gradual titration based on response and tolerability. Max: 6 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In one randomized, controlled trial of pediatric patients with early-onset schizophrenia, schizoaffective disorder, or schizophreniform disorder, children 8 to 11 years received 0.5 mg/day PO on Day 1, with an increase to 1 mg/day on Day 6, 1.5 mg/day on Day 11, and 2 mg/day on Day 15 as clinically indicated; thereafter, gradual titration occurred as needed in increments of 1 mg/day, up to 6 mg/day PO. Children 12 years received 0.5 mg/day on Day 1, with titration up to 3 mg/day by Day 11, and titration thereafter as clinically indicated in increments of 1 mg/day, up to 6 mg/day PO.

    Intramuscular depot dosage (i.e., Risperdal Consta)
    Adults

    Usual dose: 25 mg IM (deep gluteal or deltoid injection) once every 2 weeks. Establish tolerability with oral risperidone or other antipsychotic prior to IM use. Supplement with oral dose for 3 weeks after first injection to ensure that adequate plasma concentrations of depot risperidone are attained prior to discontinuation of the previous therapy. Doses above 25 mg IM every 2 weeks do not appear to provide greater efficacy; however, some adult patients not responding to the 25 mg dose may benefit from 37.5 mg or 50 mg IM once every 2 weeks. Titrate dose at a minimum of every 4 weeks; response following titration should not be expected earlier than 3 weeks. Max dose: 50 mg IM once every 2 weeks. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. GERIATRIC PATIENTS: The recommended dose is 25 mg IM once every 2 weeks. In general, no differences in tolerability have been observed between otherwise healthy geriatric versus younger adult patients. Therefore, dosing recommendations for otherwise healthy elderly patients are the same as for younger adults. Advise the patient regarding risk for orthostasis and prevention; consider monitoring at-risk geriatric patients. OTHER DOSE ADJUSTMENTS: Initiation with 12.5 mg IM may be appropriate in those with impaired renal or hepatic function, during concurrent use of medications which increase risperidone plasma levels, and in those with a history of poor tolerability to the drug. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

    Subcutaneous depot once-monthly dosage (i.e., Perseris)
    Adults

    Initiate with 90 mg or 120 mg by abdominal subcutaneous injection once monthly, administered by a health care professional. Max: 120 mg/month. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. For patients who have never taken risperidone, establish tolerability with oral risperidone prior to starting the subcutaneous injection. Neither a loading dose nor oral supplementation of risperidone is recommended during Perseris treatment. Based on average plasma concentrations of risperidone and total active moiety, Perseris 90 mg corresponds to 3 mg/day of oral risperidone and Perseris 120 mg corresponds to 4 mg/day of oral risperidone.

    For the treatment of bipolar disorder (Bipolar I Disorder), including acute mania or mixed episodes and maintenance therapy.
    For the treatment of acute mania or mixed episodes associated with Bipolar I Disorder.
    Oral dosage
    Adults

    Initially, 2 mg/day to 3 mg/day PO once daily as monotherapy or as an adjunct to lithium or valproate. If needed, adjust the dose by 1 mg/day at intervals of no less than 24 hours. A dose range of 1 mg/day to 6 mg/day PO was evaluated and found effective in clinical trials; higher doses were not studied. Individualize according to response and tolerability. Slower titration or divided daily doses may be needed in some patients. Use the lowest effective dosage. Efficacy of risperidone as monotherapy for manic episodes was demonstrated in two 3-week, randomized, controlled trials. The mean modal dose ranged from 4.1 mg/day to 5.6 mg/day. Results from one study indicate that risperidone 6 mg has equivalent efficacy to lithium (800 mg/day to 1200 mg/day) and haloperidol (10 mg/day) in the monotherapy treatment of acute mania. In a 3-week, double-blind controlled trial, risperidone plus a mood stabilizer (i.e., lithium or divalproex) was shown to be more efficacious than a mood stabilizer alone and as efficacious as haloperidol plus a mood stabilizer for the rapid control of manic symptoms as assessed by the Young Mania Rating Scale (YMRS). Further significant reductions in the YMRS were seen during the 10-week, open-label extension phase of treatment with risperidone plus a mood stabilizer. Concerns about extrapyramidal symptoms have been noted in bipolar clinical trials; lower doses in bipolar disorder (vs. schizophrenia) should be considered. In general, pharmacological treatment is continued beyond acute stabilization; however, there are no systematically obtained data to support the use of risperidone beyond 3 weeks. Periodically re-assess the need for continued treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Geriatric Adults

    Initially, 0.5 mg PO twice per day followed by careful titration. If needed, adjust the dose by 1 mg/day at intervals of no less than 24 hours. Slower titration or divided doses may be needed in geriatric patients due to the potential for impaired renal function and an increase in drug toxicity. A dose range of 1 mg/day to 6 mg/day PO was evaluated and found effective in clinical trials in younger adults; higher doses were not studied. Individualize according to response and tolerability. Use the lowest effective dosage. Efficacy of risperidone as monotherapy or along with a mood stabilizer (i.e., lithium or divalproex) has been noted in trials for acute mania. Further significant reductions in the YMRS were seen during the 10-week, open-label extension phase of treatment with risperidone plus a mood stabilizer. Concerns about extrapyramidal symptoms have been noted in bipolar clinical trials; lower doses in bipolar disorder (vs. schizophrenia) should be considered. In general, pharmacological treatment is continued beyond acute stabilization; however, there are no systematically obtained data to support the use of risperidone beyond 3 weeks. Periodically re-assess the need for continued treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Children and Adolescents 10 to 17 years

    Initially, 0.5 mg PO once daily in the morning or evening as monotherapy. May administer in divided doses to increase tolerability. Adjust dose at intervals of at least 24 hours and in increments of 0.5 mg/day to 1 mg/day as tolerated to the recommended target dose range of 1 mg/day to 2.5 mg/day PO. Doses above 2.5 mg/day do not appear to provide additional therapeutic benefits and may result in more adverse events. Doses above 6 mg/day PO have not been studied. Safety and efficacy of risperidone as an adjunct treatment to lithium or valproate in pediatric patients have not been established. Safety and efficacy of the drug beyond 3 weeks in adolescents have not been systematically evaluated. Individualize dose according to response and tolerability. Use the lowest effective dosage. In general, pharmacological treatment is continued beyond acute stabilization; however, there are no systematically obtained data to support the use of risperidone in longer-term treatment (i.e., beyond 3 weeks). Periodically re-assess the need for continued treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the maintenance treatment of Bipolar I Disorder as monotherapy or adjunct therapy to lithium or valproate.
    Intramuscular depot dosage (i.e., Risperdal Consta)
    Adults

    Establish tolerability with oral risperidone prior to converting to IM extended-release risperidone (Risperdal Consta) in patients who have never received risperidone. Then initiate Risperdal Consta with 25 mg IM every 2 weeks. Oral risperidone (or another antipsychotic) should be given with the first injection of Risperdal Consta, and continued for 3 weeks to ensure adequate therapeutic plasma concentrations from Risperdal Consta. Some patients may benefit from doses of 37.5 mg to 50 mg IM every 2 weeks. Upward dose adjustments should not be made more frequently than every 4 weeks. Dosages above 50 mg every 2 weeks have not been studied in this patient population. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. GERIATRIC PATIENTS: The recommended dose for geriatric patients is 25 mg IM once every 2 weeks. During clinical trial evaluation, no differences in tolerability were observed between otherwise healthy geriatric versus younger adult patients. Therefore, dosing recommendations for otherwise healthy elderly patients are the same as for younger adults. However, because elderly patients have a greater tendency towards orthostatic hypotension, instructions on preventative measures for orthostasis should be provided. Monitoring of orthostatic vital signs should be considered in elderly patients for whom orthostatic hypotension is a concern. OTHER DOSE ADJUSTMENTS: A lower initial dose of 12.5 mg may be appropriate for those with renal impairment, hepatic impairment, a history of poor tolerability to psychotropic medications, or regimens with the potential for drug interactions with risperidone. It should be noted that efficacy of the 12.5 mg dose has not been established. Re-evaluate the need for continued treatment during long-term use.

    For the treatment of irritability associated with autistic disorder.
    Oral dosage
    Children and Adolescents 5 to 17 years and weighing 20 kg or more

    0.5 mg PO once daily, initially, for at least 4 days. Then may increase to recommended dose of 1 mg PO daily. May administer in divided doses to increase tolerability. Maintain this dose for at least 14 days. Thereafter, adjust as clinically necessary at intervals of at least 2 weeks and increments of 0.5 mg/day PO. Effective dose range: 0.5 mg to 3 mg/day PO. Once sufficient clinical response has been achieved and maintained, consider gradually lowering the dose to achieve the optimal balance of safety and efficacy, and periodically re-assess during long-term treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Children and Adolescents 5 to 17 years and weighing 15 to 19 kg

    0.25 mg PO once daily, initially, for at least 4 days. Then may increase to recommended dose of 0.5 mg PO daily. May administer in divided doses to increase tolerability. Maintain this dose for at least 14 days. Thereafter, adjust as clinically necessary at intervals of at least 2 weeks and increments of 0.25 mg/day PO. Effective dose range: 0.5 mg to 3 mg/day PO. Once sufficient clinical response has been achieved and maintained, consider gradually lowering the dose to achieve the optimal balance of safety and efficacy, and periodically re-assess during long-term treatment. No dosing data are available for autistic disorder in pediatric patients weighing less than 15 kg. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of moderate to severe tics associated with Tourette's syndrome† or chronic tic disorders†.
    Oral dosage
    Adults

    A dosage range of 0.25 mg to 6 mg per day PO is recommended in evidence-based guidelines for the treatment of tic disorders. Initiate at the low end of the dosage range and titrate to response and tolerability. Results from small randomized studies suggest that the mean effective dose is approximately 2.5 to 4 mg/day. In one study, a mean risperidone dose of 3.8 mg/day (range: 0.5 mg/day to 6 mg/day) was similar in efficacy to a mean pimozide dose of 2.9 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The American Academy of Neurology (AAN) practice guideline states that risperidone is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; however, there is insufficient evidence to determine the efficacy of risperidone relative to other antipsychotics used to treat tics.

    Children and Adolescents 7 to 17 years


    Low initial doses are suggested (e.g., 0.25 to 0.5 mg/day PO); the usual effective dose range is 1 to 4 mg/day. Results from small randomized studies suggest the mean effective dose is approximately 2.5 mg/day. A separate study that included adolescents 14 years and older used a maximum of 6 mg/day PO; a median dose of 2.5 mg/day (range 1 to 6 mg/day) was superior to placebo. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. The American Academy of Child and Adolescent Psychiatry (AACAP) recommends atypical antipsychotics as a treatment option for patients with moderate to severe tics and in patients with tics with other comorbidities suitable for treatment with an antipsychotic. The American Academy of Neurology (AAN) practice guideline states that risperidone is probably more likely than placebo to reduce tic severity in patients with Tourette's syndrome or chronic tic disorders; however, there is insufficient evidence to determine the efficacy of risperidone relative to other antipsychotics used to treat tics.

    For the treatment of moderate to severe disruptive behaviors† (e.g., aggression) associated with oppositional defiant disorder† or other disruptive behavioral disorders†.
    Oral dosage
    Adolescents

    In one study, body weight was used to determine dosage. Those weighing less than 50 kg received 0.25 mg/day PO initially; if weight 50 kg or more, 0.5 mg/day PO was given initially. Thereafter, the dose was increased gradually by 0.25 mg for patients less than 50 kg or 0.50 mg for those weighing 50 kg or more to a maximum daily dose of 0.75 mg/day PO for patients less than 50 kg or 1.5 mg/day PO for those 50 kg or more. The mean risperidone dosage was approximately 0.02 mg/kg/day.] Doses have varied among studies. In a comprehensive review, the mean risperidone dose ranged from 0.98 to 1.5 mg/day at study end for all studies evaluated. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    Children 5 to 12 years

    0.01 mg/kg/day PO for at least 2 days is a suggested initial weight-based dose. Then, may titrate to 0.02 mg/kg/day for 5 days, and subsequently adjust weekly as clinically indicated by 0.02 mg/kg/day. Max: 0.06 mg/kg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In one study, body weight was used to determine dosage. Those weighing less than 50 kg received 0.25 mg/day PO initially; if weight was 50 kg or more, 0.5 mg/day PO was given initially. Thereafter, the dose was increased gradually by 0.25 mg for patients less than 50 kg or 0.5 mg for those weighing 50 kg or more to a maximum daily dose of 0.75 mg/day PO for patients less than 50 kg or 1.5 mg/day PO for those 50 kg or more. The mean risperidone dosage was approximately 0.02 mg/kg/day.] Doses have varied among studies, with mean risperidone doses ranging from 0.98 to 1.7 mg/day at the end of the studies. In a double-blind, placebo-controlled study of 110 children with a disruptive behavior disorder (DBD) and subaverage IQ, the decline in symptom ratings was 47.3% in the risperidone group vs. 20.9% in the placebo group. At study end, 25% of children in the placebo group were rated by the investigator as improved to some degree compared to 77% of children in the risperidone group. Some data have demonstrated sustained long-term improvement. In a 9-week randomized trial of 168 children (age: 6 to 12 years) with attention-deficit/hyperactivity disorder (ADHD) and a DBD (ODD or conduct disorder), the addition of risperidone to a psychostimulant and parent training showed significant improvements in measures of aggression and serious behavioral problems compared to those receiving stimulant and parent training only. Risperidone therapy (mean dose: 1.7 +/- 0.75 mg/day) was added at weeks 4 to 6 only if there was a need for improvement. For children weighing less than 25 kg, risperidone 0.5 to 2.5 mg/day was given; for children 25 kg or more, doses ranged from 0.5 to 3.5 mg/day. In a post-hoc analysis of children with ADHD and a DBD, risperidone-treated children had clinically and statistically significant reductions in disruptive behavior and hyperactivity subscale scores compared to placebo, regardless of concomitant stimulant use. However, further study is needed on the use of risperidone in the treatment of ADHD. Efficacy in children with ADHD alone or in long term settings has not been established, and the drug is not without adverse effects.

    For the treatment of delirium† in the pediatric intensive care unit (PICU).
    Oral dosage
    Children and Adolescents

    Limited data available, particularly in young children. Maintenance doses ranging from 0.2 to 2 mg/day PO have been reported as efficacious with no adverse events noted (n = 30; age range: 4 months to 17 years). One small case series (n = 11; age range: 4 months to 16 years) used a loading dose of 0.1 to 0.2 mg PO. Begin at the lower end of the dosing range for younger, smaller patients. A mode individual dose of 0.5 mg has been reported in a small case series of older children and adolescents (n = 6; age range: 5 to 15 years). Some experts have suggested 0.5 to 2.5 mg/day PO given in 2 to 4 divided doses for patients 5 to 16 years of age. Max dosing is based on weight: less than 20 kg = 1 mg/day; 20 to 45 kg = 2.5 mg/day; more than 45 kg = 3 mg/day. In a review of data from 110 seriously-ill patients with delirium who were treated with atypical antipsychotics, a limited number of the same or lower doses were used as needed to control persistent symptoms and a routine daily dose was established based on the total amount needed to gain control of symptoms. Of those receiving risperidone (n = 13; mean age: 8.6 years; range: 1 to 16 years), a mean starting dose of 0.6 mg/day (range: 0.25 to 1 mg/day), mean ending dose of 0.7 mg/day (range: 0.25 to 2 mg/day), mean maximum dose of 1 mg/day (range: 0.25 to 2 mg/day), and average dose of 1.3 mg/day (range: 0.375 to 4 mg/day) was used. Antipsychotic was discontinued as soon as possible; mean length of therapy was 17.5 days (range: 2 to 54 days). Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

    For the treatment of severe behavioral or psychological symptoms of dementia†.
    Oral dosage
    Geriatric Adults

    If treatment is deemed necessary, 0.25 mg PO once or twice daily is a common initial dose. Based on study findings, risperidone 1 mg/day to 2 mg/day PO, given in divided doses, is more efficacious than placebo in improving dementia-related behavioral symptoms, especially psychosis and aggression. Suggested Max: 2 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. According the Agency for Healthcare Research and Quality efficacy review, risperidone is efficacious as treatment for behavioral symptoms of dementia. Risperidone is the only atypical antipsychotic with moderate to high quality in strength of evidence in efficacy of all 3 dementia categories reviewed: dementia-overall behavioral symptoms, dementia-psychosis symptoms, and dementia-agitation symptoms. Antipsychotics are not FDA-approved for this indication and the labeling of all antipsychotics contains a boxed warning noting an increased risk of death in geriatric patients being treated for behavioral problems associated with dementia. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antipsychotics in long-term care facility (LTCF) residents with dementia-related behavioral symptoms. OBRA Max: 2 mg/day PO in residents meeting the OBRA criteria for treatment, except when documentation is provided showing that higher doses are necessary to maintain or improve the resident's functional status. In addition, the facility must attempt a gradual dose reduction (GDR) in 2 separate quarters, at least 1 month apart, within the first year of admission to the facility or after the facility has initiated an antipsychotic, unless clinically contraindicated. After the first year, a GDR must be attempted annually unless clinically contraindicated. The GDR may be considered clinically contraindicated if the target symptoms returned or worsened after the most recent GDR attempt within the facility and the physician has documented justification for why attempting additional dose reductions at that time would likely impair the resident's function or increase distressed behavior.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    16 mg/day PO for schizophrenia; 6 mg/day PO for bipolar disorder; 50 mg depot IM (Risperdal Consta) every 2 weeks for schizophrenia or bipolar disorder; 120 mg depot subcutaneously (Perseris) once monthly for schizophrenia.

    Geriatric

    16 mg/day PO for schizophrenia; 6 mg/day PO for bipolar disorder; 50 mg depot IM (Risperdal Consta) every 2 weeks for schizophrenia or bipolar disorder; 120 mg depot subcutaneously (Perseris) once monthly for schizophrenia.

    Adolescents

    6 mg/day PO for schizophrenia or bipolar I disorder; 3 mg/day PO for autistic disorder; 0.06 mg/kg/day PO has been suggested for the treatment of tics or severe behavior disorders associated with Tourette's or ADHD; safety and efficacy of injectables have not been established.

    Children

    10 to 12 years: 6 mg/day PO for bipolar I disorder; 3 mg/day PO for autistic disorder; 0.06 mg/kg/day PO has been suggested in developmental disability with severe disruptive behaviors; safety and efficacy of injectables have not been established.
    5 to 9 years: 3 mg/day PO for autistic disorder; 0.06 mg/kg/day PO has been suggested in developmental disability with severe disruptive behaviors; safety and efficacy of injectables have not been established.
    1 to 4 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Oral formulations: In adult patients with a Child Pugh score of 10 to 15, the recommended initial starting dose is 0.5 mg PO twice daily; titrate in increments of 0.5 mg or less. For doses more than 1.5 mg PO twice daily, titrate in weekly intervals. Specific guidelines for pediatric patients are not available.
     
    Intramuscular depot injection (Risperdal Consta): Adult patients with hepatic impairment should be treated with titrated doses of oral risperidone prior to initiating treatment with IM depot risperidone. In adults, the recommended oral titration starting dose is 0.5 mg PO twice a day during week 1; increase to 1 mg PO twice a day or 2 mg PO once daily during week 2. If at least 2 mg/day PO is well tolerated, 25 mg IM every 2 weeks may be considered; higher dosages are not recommended. Continue oral risperidone for 3 weeks after the first depot injection, then discontinue. A slower titration beginning with 12.5 mg IM may be more appropriate for some patients. Efficacy of the 12.5 mg dose has not been evaluated in clinical trials.
     
    Subcutaneous depot injection once-monthly (Perseris): Prior to initiating treatment, it is advisable that adult patients with hepatic impairment be carefully titrated up to at least 3 mg/day PO risperidone. If the patient can tolerate 3 mg/day PO risperidone and is psychiatrically stable, a dose of 90 mg subcutaneously once monthly may be considered. The subcutaneous depot injection has not been studied in patients with hepatic impairment.

    Renal Impairment

    Oral formulations: In adult patients with a CrCl less than 30 mL/minute, the recommended initial starting dose is 0.5 mg PO twice daily; titrate in increments of 0.5 mg or less. For doses more than 1.5 mg PO twice daily, titrate in weekly intervals. Specific guidelines for pediatric patients are not available.
     
    Intramuscular depot injection (Risperdal Consta): Adult patients with renal impairment should be treated with titrated doses of oral risperidone prior to initiating treatment with IM depot risperidone. In adults, start with 0.5 mg PO twice a day during week 1; increase to 1 mg PO twice a day or 2 mg PO once daily during week 2. If a dose of at least 2 mg/day PO is well tolerated, 25 mg IM every 2 weeks of the depot injection may be considered. Continue oral risperidone for 3 weeks after the first depot injection, then discontinue. A slower titration beginning with 12.5 mg IM may be more appropriate for some patients. Efficacy of the 12.5 mg dose has not been evaluated in clinical trials.
     
    Subcutaneous depot injection once-monthly (Perseris): Prior to initiating treatment, it is advisable that adult patients with renal impairment be carefully titrated up to at least 3 mg/day PO risperidone. If the patient can tolerate 3 mg/day PO risperidone and is psychiatrically stable, a dose of 90 mg subcutaneously once monthly may be considered. The subcutaneous depot injection has not been studied in patients with renal impairment.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Conventional Tablets: May be administered without regard to meals.
     
    Orally-disintegrating tablets (ODT, e.g., Risperdal M-tab):
    Do not open the blister or child-resistant pouch until ready to administer. Peel back foil to expose the tablet. Do not push the tablet through the foil because this could damage the tablet. Using dry hands, remove the tablet from the package unit.
    Immediately place the entire tablet on the tongue. Allow the tablet to disintegrate in the mouth (will occur within seconds); the patient can then swallow the dissolved medicine with or without liquid. The patient should not split or chew the tablet.

    Oral Liquid Formulations

    Oral solution:
    Can be administered directly from the calibrated pipette, or can be mixed with a beverage prior to administration. The minimum volume accurately measured with the pipette is 0.25 mL and the maximum is 3 mL.
    Compatible beverages for dilution include water, coffee, orange juice, and low-fat milk.
    The solution is NOT compatible with cola or tea.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intramuscular Administration

    Reconstitution, Preparation, Administration, and Disposition Instructions for the Risperdal Consta Single-Use Dose Pack:
    Only for intramuscular (IM) administration; do not administer intravenously. Avoid inadvertent injection into a blood vessel.
    Do not substitute any components of the dose pack, including the Risperdal Consta vial, the pre-filled syringe with 2 mL of diluent for Risperdal Consta, the vial adapter, and the 2 Terumo SurGuard needles for IM injection.
    To ensure correct dose delivery, administer full contents of the vial. Administer immediately after reconstitution.
    Prior to admixing, remove dose pack from refrigerator and allow to come to room temperature for at least 30 minutes. Do not allow to warm any other way.
    Remove cap from vial: Flip off colored cap from the vial without removing grey rubber stopper. Wipe top of grey stopper with an alcohol swab and allow to air dry.
    Prepare vial adapter: Hold sterile blister; peel back and remove the paper backing. Do not remove vial adapter from blister. Do not touch the spike tip. This will result in contamination.
    Connect vial adapter to vial: Place vial on a hard surface and hold by the base. Center the vial adapter over the grey rubber stopper and push straight down onto the vial top until it snaps securely into place. Do not place the vial adapter at an angle or diluent may leak upon transfer to vial.
    Remove sterile blister: Remove vial adapter from sterile blister only when ready to remove the white cap from prefilled syringe. Keep vial vertical to prevent leaks. Hold base of vial and pull up on the sterile blister to remove. Do not shake. Do not touch exposed luer opening on vial adapter. This will result in contamination.
    Use proper grip: Hold by white collar at the tip of the syringe. Do not hold syringe by the glass barrel during assembly.
    Remove cap: Holding the white collar, snap off white cap; do not twist or cut off. Do not touch syringe tip due to contamination. Discard broken off cap.
    Connect syringe to vial adapter: Hold vial adapter by skirt to keep stationary. Hold syringe by white collar then insert tip into the luer opening of the vial adapter. Do not hold glass syringe barrel. This may cause white collar to loosen or detach. Attach syringe to vial adapter with a firm clockwise twisting motion until it feels snug. Do not over-tighten since this may cause the syringe tip to break.
    Inject diluent: Inject entire amount of diluent from syringe into vial. Vial contents will now be under pressure. Keep holding down the plunger rod with thumb.
    Suspend microspheres in diluent: While holding down the plunger rod, shake vigorously for at least 10 seconds. The suspension should appear uniform, thick and milky in color. Microspheres will be visible in the liquid. Immediately proceed to next step to keep suspension from settling.
    Transfer suspension to syringe: Invert vial completely. Slowly pull plunger rod down to withdraw entire contents from the vial into syringe.
    Remove vial adapter: Hold white collar on the syringe and unscrew from vial adapter. Tear section of vial label at the perforation and apply to syringe for ID. Discard both vial and vial adapter appropriately.
    Select and attach needle: Use 1-inch needle for deltoid and 2-inch needle for gluteal administration. Peel blister pouch partially and use to grasp base of needle. Holding the white collar on the syringe, attach syringe to needle luer connection with a firm clockwise twisting motion until snug. Do not touch needle luer opening.
    Just before injection - re-suspend injection suspension microspheres: Settling will occur after reconstitution. Fully remove blister pouch. Just before injection, shake syringe vigorously.
    Remove transparent needle protector: Move needle safety device back towards the syringe. Then hold white collar on syringe and carefully pull the transparent needle protector straight off.
    Remove air bubbles: Gently tap the syringe and slowly depress the plunger with the needle in an upright position.
    Inject: Immediately inject (to avoid settling) entire contents of syringe in the upper outer quadrant of the gluteal area or the deltoid muscle of the arm.
    Secure needle in safety device and discard: Using 1 hand, place needle safety device at a 45-degree angle on a hard, flat surface. Press down with a firm, quick motion until the needle is fully engaged in safety device. Check to confirm needle safety device is fully engaged. Discard in an approved sharps container along with unused needle in dose pack.
    Avoid a needle stick injury: Do not use 2 hands. Do not intentionally disengage or mishandle the needle safety device. Do not straighten the needle or engage the safety device if the needle is bent or damaged.
    Dispose of properly: Do not re-use dose pack components since this may affect device integrity or lead to performance deterioration.
    Rotate injection sites: Alternate site with each injection. Alternate gluteal injections between buttocks and alternate arms between deltoid injection.
    Refer to the Instructions for Use section of the product labeling for detailed visual aids which accompany the written instructions.

    Subcutaneous Administration

    Reconstitution, Preparation, Administration, and Disposition Instructions for Perseris Single-Dose Kit:
    For abdominal subcutaneous injection only. Do NOT administer by any other route.
    Each injection must be administered by a healthcare professional.
    Do not substitute any components of the prepackaged single-dose kit, which includes 1 liquid syringe pre-filled with the delivery system, one powder syringe pre-filled with risperidone powder, and 1 sterile 18-gauge, 5/8-inch safety needle.
    As a universal precaution, always wear gloves.
    Neither a loading dose nor supplemental oral risperidone is recommended. A patient who misses a dose should receive the next dose as soon as possible.
    Allow package to come to room temperature for at least 15 minutes prior to preparation. Only prepare medication when you are ready to administer the dose.
    Tap Powder Syringe: Hold syringe upright and tap the barrel of the syringe to dislodge any powder that became packed during shipping.
    Uncap Liquid and Powder Syringes: Remove cap from liquid syringe, then remove cap from powder syringe. Holding both syringes in your non-dominant hand can help with this step.
    Connect the Syringes: Place liquid syringe on top of the powder syringe to prevent powder spillage and connect the syringes by twisting about 3/4 turn.
    Premixing the Product: Failure to fully mix the medication could result in the incorrect dosage.
    Transfer contents of the liquid syringe into the powder syringe.
    Gently push the powder syringe plunger until you feel resistance (to wet powder and avoid compacting).
    Repeat this gentle back-and-forth process for 5 cycles.
    Complete Mixing: Continue mixing syringes for an additional 55 cycles. This mixing can be more vigorous than when premixing.
    When fully mixed, the suspension should be cloudy and uniform in color.
    Color may vary from white to yellow-green.
    If clear areas are seen in the mixture, mix until the color distribution is uniform.
    Prepare Injection Syringe: Failure to aspirate the liquid from the powder syringe may result in an incorrect dosage. 
    First, transfer all contents into the liquid syringe. 
    Next, perform the following 2 actions SIMULTANEOUSLY: maintain slight pressure on the powder syringe plunger, AND pull back gently on the liquid syringe plunger while twisting the syringes apart.
    Finally, attach the safety needle by twisting until finger tight.
    Check that the medication is uniform in color and free from foreign particles.
    Prepare the Abdominal Injection Site: Choose an injection site on the abdomen with adequate subcutaneous tissue free of skin conditions. It is recommended that the patient is in the supine position. Do not inject into an area where the skin is irritated, reddened, bruised, infected, or scarred in any way.
    Clean injection site well with an alcohol pad. 
    Rotate injection sites following a pattern similar that shown in the product labeling to help minimize irritation.
    Remove Excess Air from Syringe: Hold syringe upright for several seconds to allow air bubbles to rise.
    Remove needle cover and slowly depress the plunger to push out excess air from syringe.
    If medication is seen at needle tip, pull back slightly on the plunger to prevent medication spillage.
    Bubbles will not rise as quickly as those in an aqueous solution due to suspension viscosity.
    Pinch Injection Site: Pinch enough skin around injection area to accommodate needle size. Lift adipose tissue from underlying muscle to prevent IM injection.
    Inject the Medication: Insert needle fully into the subcutaneous tissue. Inject medication slow and steady. Actual angle of injection will depend on the amount of subcutaneous tissue.
    Withdraw Needle: Withdraw the needle at the same angle used for insertion and release pinched skin. Do not rub injection area after injection. If bleeding occurs, apply a gauze pad or bandage, but use minimal pressure.
    Lock the Needle Guard and Dispose of Syringe: Lock the needle guard into place by pushing it against a hard surface. Dispose of all syringe components in a secure sharps disposal container.
    Instruct the Patient: Advise the patient that they may have a lump for several weeks that will decrease in size over time. It is important that the patient not rub or massage the injection site and to be aware of the placement of any belts or clothing waistbands.
    Refer to the Instructions for Use section of the product labeling for detailed visual aids which accompany the written instructions.

    STORAGE

    Generic:
    - Protect from light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 degrees F)
    PERSERIS:
    - See package insert for detailed storage information
    - Store in refrigerator (36 to 46 degrees F) or at 77 degrees F, excursions permitted 59 to 86 degrees F
    Risperdal:
    - Protect from light
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Risperdal Consta:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard reconstituted product if not used within 6 hours
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    - Store at temperatures not exceeding 77 degrees F for no more than 7 days if refrigeration is not available
    Risperdal M-Tab:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Serious hypersensitivity reactions or anaphylaxis

    Risperidone is contraindicated in patients with a known hypersensitivity to risperidone or paliperidone, or to any of the excipients in the risperidone formulation. There is a risk of serious hypersensitivity reactions or anaphylaxis. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been observed in patients treated with risperidone and in patients treated with paliperidone. Paliperidone is an active metabolite of risperidone; therefore, cross-sensitivity is likely.

    CNS depression, coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion

    Risperidone has the potential to impair cognitive and motor skills. The sedative effects of risperidone may be most evident in the initial days of treatment. Patients should be advised to use caution when engaging in activities requiring coordination and concentration, such as driving or operating machinery, until they know how this drug affects them. Somnolence due to antipsychotic use could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate somnolence. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. In general, avoid use in patients with significant CNS depression. Given the primary CNS effects of risperidone, caution should be used during coadministration with other CNS depressants and alcohol. Ethanol ingestion may further impair cognitive and motor skills and patients should be advised to avoid use of alcoholic beverages.

    Abrupt discontinuation

    Abrupt discontinuation of antipsychotics is generally not advisable unless required by the patient's medical condition. Abrupt discontinuation of antipsychotics can be associated with withdrawal dyskinesias and a risk of developing neuroleptic malignant syndrome. Because of the strong alpha-adrenergic receptor blocking effects of risperidone, abrupt discontinuation may cause rebound anxiety, restlessness, sweating, tremors, abdominal pain, heart palpitations, headache, and increased blood pressure. During drug discontinuation, patients should be carefully observed for the recurrence of symptoms from the psychiatric disorder (e.g., schizophrenia, bipolar disorder) being treated. A drug withdrawal syndrome (unspecified) was reported during clinical trial evaluation of risperidone; however, the frequency is unknown and causality to the drug has not been established.

    Tardive dyskinesia

    Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotics. Periodic evaluation for movement disorders is recommended (e.g., AIMS). Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the initiation of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotics differ in their potential to cause tardive dyskinesia is unknown. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotics administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief periods at low doses or may even arise after drug discontinuation. The syndrome may remit, partially or completely, if the antipsychotic is withdrawn. Antipsychotics may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, risperidone should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that is known to respond to antipsychotics, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic therapy, the smallest dose and the shortest duration producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically. If signs and symptoms of tardive dyskinesia appear, risperidone discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

    Cardiac disease, cerebrovascular disease, heart failure, hypotension, hypovolemia, myocardial infarction, orthostatic hypotension, syncope

    Secondary to alpha-blockade, risperidone can inhibit vasoconstriction and can produce vasodilation. The resultant drop in blood pressure through decreased peripheral resistance can precipitate orthostatic hypotension associated with dizziness, tachycardia, and, in some patients, syncope. This effect may especially occur during the initial dose-titration period. Limiting the initial risperidone dose and titration of the dosage according to recommended schedules might minimize the risk of orthostatic hypotension and syncope. Monitoring of orthostatic vital signs should be considered in patients for whom hypotension is of concern. Orthostatic hypotension could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate orthostasis. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider dose reduction if hypotension occurs. Use with particular caution in patients with known cardiac disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, or with conditions that would predispose patients to hypotension (e.g., dehydrated state or hypovolemia). Of note, heart failure and myocardial infarction may also increase the risk of prolonging the QT interval when using risperidone. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothyroidism, long QT syndrome, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Use risperidone with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, abnormally low body temperature, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Pooled data from controlled trials indicate there are no statistically significant differences in mean changes from baseline in ECG parameters including QT, corrected QT (QTc), and PR intervals when risperidone is compared to placebo. However, postmarketing reports of overdose indicate that QT prolongation and torsade de pointes (TdP) have occurred. Paliperidone, the active metabolite of risperidone, modestly increases the QTc interval. Causality has not been established; however, one expert source considers risperidone to have a conditional risk for QT prolongation and TdP because there are reports of TdP in risperidone-treated patients who also have bradycardia, hypokalemia, hypomagnesemia, or are receiving other medications known to prolong the QT interval.[59321]

    Agranulocytosis, hematological disease, leukopenia, neutropenia, thrombotic thrombocytopenic purpura (TTP)

    Risperidone should be used with caution in patients with a hematological disease. Hematologic effects including leukopenia, neutropenia, and agranulocytosis (severe neutropenia) have been associated with antipsychotic use. A history of drug-induced leukopenia or neutropenia or pre-existing low white blood cell (WBC) count may increase the likelihood of developing hematologic effects during treatment with an antipsychotic medication. Patients with a history of clinically significant low WBC count or drug-induced leukopenia/neutropenia should have frequent complete blood count (CBC) assessments during the first few months of treatment. Consider discontinuation of the antipsychotic if a clinically significant decline in WBC occurs in the absence of an identifiable cause. Monitor patients with clinically significant neutropenia closely for fever and infection, and institute appropriate medical intervention if necessary. Discontinue risperidone in patients with severe neutropenia (ANC less than 1,000/mm3); provide ongoing medical care and follow the WBC count until neutropenia resolves. A single case of thrombotic thrombocytopenic purpura (TTP) was reported in an adult patient receiving oral risperidone in a large, open premarketing experience (approximately 1,300 patients); the patient eventually recovered after receiving plasmapheresis. The relationship to risperidone therapy is unknown.

    Hyponatremia, seizure disorder, seizures

    Patients with a history of seizures or with a known seizure disorder should be treated cautiously with risperidone. In clinical trials, risperidone was associated with seizures in a small number of adult patients (0.3%); 2 cases occurred in association with hyponatremia. Seizures have also been reported during postmarketing use.

    Renal disease, renal failure, renal impairment

    Because the active metabolite of risperidone is substantially excreted by the kidneys, the risk of toxicity is greater in patients with renal disease or renal impairment, including renal failure. In adult patients with moderate to severe renal impairment (CrCl 15 to 59 mL/minute), the clearance of oral risperidone and its active metabolite is decreased by 60% compared to healthy subjects. Reduced oral dosages are recommended for adult patients with severe renal impairment (CrCl less than 30 mL/minute). The manufacturers of the extended-release intramuscular injection (Risperdal Consta) and extended-release subcutaneous injection (Perseris) recommend careful titration with oral risperidone in patients with renal impairment before depot therapy is initiated. Guidelines for adjustments in pediatric patients are not available.

    Hepatic disease

    In adult patients with hepatic disease, the mean free fraction of risperidone in plasma is increased by about 35%. Therefore, reduced oral dosages are recommended for adult patients with hepatic disease. The manufacturers of the extended-release intramuscular injection (Risperdal Consta) and extended-release subcutaneous injection (Perseris) recommend careful titration with oral risperidone in patients with hepatic impairment before depot therapy is initiated. Guidelines for dosage adjustment in pediatric patients are not available.

    Ambient temperature increase, dehydration, hyperthermia, hypothermia, strenuous exercise

    Antipsychotics have been reported to disrupt the body's ability to reduce core body temperature presumably through effects in the hypothalamus, and they predispose patients to hyperthermia. Patients receiving risperidone should be advised of conditions that contribute to an elevation in core body temperature (e.g., strenuous exercise, ambient temperature increase, or dehydration). A less frequently described alteration in thermoregulatory processes reported with both conventional and atypical antipsychotics is hypothermia. Thermoregulation is multi-factorial; however, the dopaminergic system appears to have a primary role, and serotonin may also have modulatory activity (5-HT2a receptors). Most cases of hypothermia associated with antipsychotics have occurred in conjunction with other potential precipitating factors such as hypothyroidism, sepsis, organic brain injury, or environmental temperature. Hypothermia appears to occur more frequently during initiation of antipsychotic therapy or after dose increases. Hypothermia may also increase the risk of prolonging the QT interval when using risperidone.  

    Dysphagia

    Patients with dysphagia or who are at risk for aspiration pneumonia should be closely monitored while receiving risperidone. Esophageal dysmotility and aspiration of gastric contents have been associated with antipsychotic use, which may increase the incidence of aspiration pneumonia in certain patient populations, such as elderly patients with advanced Alzheimer's disease.

    Neurological disease, Parkinson's disease

    Antipsychotics can cause motor and sensory instability, which may lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with diseases (e.g., neurological disease), conditions, or concurrent medication use that could exacerbate motor and sensory instability. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Risperidone should be used with caution in patients with Parkinson's disease because of possible development of extrapyramidal symptoms. However, atypical antipsychotics such as risperidone are less likely to interfere with treatments for Parkinson's disease than traditional antipsychotic agents. In general, avoid risperidone use during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.

    Dementia, geriatric

    Reported clinical experience has not identified differences in responses between elderly and younger patients receiving oral or injectable risperidone. In general, a lower starting dose is recommended for the geriatric patient, reflecting a decreased drug clearance in the elderly. Orthostatic risk in the elderly may be minimized using a lower initial dose of risperidone followed by careful titration. Monitor blood pressure and renal function. Antipsychotics, including risperidone, are not approved for the treatment of dementia-related psychosis in geriatric patients. All atypical antipsychotic labels include a boxed warning regarding increased morbidity and mortality (1.6 to 1.7 times vs. placebo) reported in geriatric patients with dementia receiving atypical antipsychotics. Deaths typically occurred due to heart failure, sudden death, or infections (primarily pneumonia). An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has been reported. Geriatric patients may also be at increased risk for developing a prolonged QT interval when using risperidone. According to the Beers Criteria, antipsychotics are considered potentially inappropriate medications (PIMs) in elderly patients, and use should be avoided except for treating schizophrenia or bipolar disorder, and for short-term use as antiemetics during chemotherapy. Avoid use of risperidone in geriatric patients with the following conditions due to the potential for symptom exacerbation or adverse effects: delirium (possible new-onset or worsening delirium), dementia (adverse CNS effects), and Parkinson's disease (symptom exacerbation). There is an increased risk of stroke and a greater rate of cognitive decline and mortality in persons with dementia receiving antipsychotics. The Beers expert panel recommends avoiding antipsychotics to treat delirium- or dementia-related behavioral problems unless non-pharmacological options have failed or are not possible and the patient is a substantial threat to self or others. Avoid antipsychotics in elderly patients with a history of falls or fractures unless safer alternatives are not available since antipsychotics can cause ataxia, impaired psychomotor function, syncope, and new falls. If use is necessary, consider reducing the use of other CNS-active medications and implement other strategies to reduce fall risk. Because antipsychotics can cause or exacerbate hyponatremia and SIADH, particularly in the elderly, sodium levels should be closely monitored when starting or changing dosages of antipsychotics in older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). An antipsychotic should generally be used only for the conditions listed in the guidelines (e.g., schizophrenia, mood disorder, Tourette's disorder) and meet the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for use. The LTCF must identify and address all possible causes of behavioral or psychological symptoms of dementia (BPSD) before considering an antipsychotic, as there is an increased risk of morbidity and mortality in elderly patients treated with antipsychotics for dementia-related psychosis. To initiate antipsychotic therapy, the patient must either be a danger to self or others or have symptoms due to mania or psychosis, and the plan of care should document attempted behavioral interventions (except in an emergency). Limit emergency treatment to 7 days or less and evaluate/document within 7 days the contributors/causes to the symptoms. For acute conditions persisting beyond 7 days, appropriate non-pharmacologic interventions must be attempted, unless clinically contraindicated and documented. Treatment of non-acute, chronic, or prolonged BPSD must meet all of the OBRA criteria for BPSD treatment and ensure that the behavioral symptoms are not due to a treatable medical condition or correctable environmental or psychological stressors alone and the facility must provide documented evidence of persistence. The LTCF must evaluate the appropriateness of antipsychotic treatment during or within 2 weeks of admission for a newly admitted resident. OBRA provides general dosing guidance for antipsychotic treatment of BPSD. In all cases, the lowest possible dose and the shortest duration should be prescribed and the facility should monitor for ongoing effectiveness and potential adverse effects. Antipsychotics are subject to periodic review for effectiveness, medical necessity/rationale for use, and the potential for gradual dose reduction (GDR) or discontinuation. Refer to the OBRA guidelines for complete information.

    Phenylketonuria

    Risperidone orally disintegrating tablets (e.g., Risperdal M-Tab ODT, others) contain aspartame, a source of phenylalanine. For example, Risperdal M-Tabs contain phenylalanine in the following quantities: each 4 mg ODT contains 0.84 mg phenylalanine; each 3 mg ODT contains 0.63 mg phenylalanine; each 2 mg ODT contains 0.42 mg phenylalanine; each 1 mg ODT contains 0.28 mg phenylalanine; and each 0.5 mg ODT contains 0.14 mg phenylalanine. Caution is advised in patients with phenylketonuria.

    Diabetes mellitus, diabetic ketoacidosis, hypercholesterolemia, hyperglycemia, hyperlipidemia, hyperosmolar hyperglycemic state (HHS), hypertriglyceridemia, obesity

    Atypical antipsychotics, including risperidone, have been associated with metabolic changes that may increase cardiovascular or cerebrovascular risk over time, including loss of blood glucose control, dyslipidemia, and weight gain. Use risperidone with caution in patients with pre-existing conditions such as obesity, pre-diabetes, established diabetes mellitus, or hyperlipidemia. All patients treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia (polydipsia, polyuria, polyphagia, weakness), worsening of glucose control, dyslipidemia, and weight gain. Evaluate weight gain against expected normal growth patterns in pediatric patients. Perform fasting blood glucose testing at the beginning of treatment in patients with risk factors for diabetes mellitus (e.g., obesity, family history). Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing. Hyperglycemia or diabetes was reported in rare instances during risperidone clinical trials. Hyperglycemia, in some cases associated with diabetic ketoacidosis or hyperosmolar hyperglycemic state (HHS) with coma or death, has been reported in patients treated with atypical antipsychotics. Hyperglycemia resolved in some cases when the antipsychotic was discontinued; however, some patients required continuation of antidiabetic agents despite discontinuation of the suspect drug. Metabolic changes in patients treated with atypical antipsychotics have also included dyslipidemias such as hypercholesterolemia and/or hypertriglyceridemia. Prior to initiating risperidone or shortly after that, obtain a fasting lipid profile. Periodic monitoring of serum lipids is recommended during long-term treatment. Inform all patients of the importance of maintaining a nutritionally balanced diet during treatment with an antipsychotic. 

    Priapism

    Priapism has been reported during postmarketing use of risperidone. Drugs with alpha-adrenergic blocking effects have been reported to induce priapism. Priapism requires medical treatment and severe cases may require surgical intervention. Advise male patients to seek medical intervention if they experience a prolonged or painful erection lasting more than 4 hours. The patient should call their healthcare provider or go to the nearest emergency room right away if this occurs.

    Breast cancer, hyperprolactinemia, infertility

    Risperidone can cause hyperprolactinemia, likely due to central dopamine D2 receptor antagonism, and is associated with higher elevations in prolactin than many other antipsychotics. Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Elevations in prolactin may result in infertility in either men or women, or other endocrine abnormalities in adults and pediatric patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both females and males. Close monitoring for adverse endocrine effects is advisable during use of risperidone. In animal studies, an increase in pituitary gland, mammary gland, and pancreatic islet cell neoplasia have been observed during administration of some antipsychotics, including risperidone, and may be mediated by prolactin. Although the clinical significance of these findings is unknown, some human breast cancers may be prolactin-dependent and therefore risperidone should be used cautiously in those who have a history of breast cancer. Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of antipsychotics and tumorigenesis in humans; however, the available evidence is considered too limited to be conclusive at this time.

    Neonates, pregnancy, pregnancy testing

    When considering the use of risperidone during pregnancy, the possibility of risperidone-related adverse outcomes in the fetus or neonate should be weighed against the risks of an untreated maternal psychiatric condition, which may include hospitalization, relapse, suicide, and increased adverse perinatal outcomes (e.g., pre-term birth). A prospective observational study of women (n = 6) treated with risperidone demonstrated placental passage of risperidone and its metabolite paliperidone. A retrospective cohort study from a Medicaid database of 9,258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects. There was a small increase in major birth defects and cardiac malformations in a subgroup of 1,566 women exposed to risperidone during their first trimester of pregnancy; however, there is no mechanism of action to explain the increased malformation rate, and the overall available data from published epidemiologic studies of pregnant women exposed to atypical antipsychotics have not established a drug-associated risk of birth defects, miscarriages, or adverse maternal or fetal outcomes. There is a human case report of agenesis of the corpus callosum occurring in utero. Neonates exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity and have ranged from self-limited to those requiring intensive care unit support and prolonged hospitalization. Neonates exhibiting signs or symptoms of extrapyramidal effects or withdrawal should be carefully monitored. The knowledge about long-term neurobehavioral effects in offspring is limited for all antipsychotic agents and requires further investigation. According to the American Psychiatric Association treatment guidelines for schizophrenia, consider pregnancy testing in women of childbearing potential prior to initiation of an antipsychotic. The National Pregnancy Registry for Psychiatric Medications is dedicated to evaluating the safety of psychiatric medications that may be taken by women during pregnancy to treat a wide range of mood, anxiety, or psychiatric disorders. The primary goal of this Registry is to determine the frequency of major malformations, such as heart defects, cleft lip, or neural tube defects, in babies exposed to various psychiatric drugs during pregnancy. While the research concentrates on atypical antipsychotics and antidepressant use, pregnant women using other psychiatric medications are encouraged to register. For more information, contact the registry at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by phone 1-866-961-2388. It is not known if antipsychotics, through their effect on prolactin, would affect labor or delivery.

    Children, infants, suicidal ideation

    Oral risperidone is indicated for use in children and adolescents 5 to 17 years of age dependent on the selected indications. Risperidone depot injections are not indicated for use in pediatric patients under 18 years of age. Adverse psychiatric effects, including aggression and suicidal behaviors (e.g., suicidal ideation, suicide attempt), have occurred in pediatric patients receiving risperidone. Although causality to the drug has not been established, careful monitoring for changes in mood and behavior is advisable as well as prescribing risperidone in the smallest quantity consistent with good management in order to reduce the risk of overdose. Close monitoring for adverse endocrine effects is advisable during use of risperidone in children and adolescents. Risperidone has been associated with hyperprolactinemia in children and adolescents; sequelae have included galactorrhea and gynecomastia. Weight gain should be evaluated against expected normal growth patterns in pediatric patients periodically during treatment. Weight gain in children and adolescents may be substantial, particularly during chronic treatment. The long-term effects of risperidone on growth and sexual maturation have not been fully evaluated; however, decreases in bone length and density, delays in sexual maturation, and impairment in cognitive performance have been documented in studies in juvenile animals. There is no known indication for the drug in infants. Additionally, adverse effects have been reported after delivery in newborns exposed to antipsychotics during the third trimester. These effects have varied in severity ranging from self-limited to requiring intensive care unit stays and prolonged hospitalization.

    Breast-feeding

    Data related to the safety of antipsychotics during breast-feeding are limited and a careful benefit to risk assessment should be performed if chronic administration of any antipsychotic is being considered. Consider the developmental and health benefits of breast-feeding along with the mother's need for risperidone and any potential drug-related adverse effects on the breast-fed child or from the mother's underlying condition. Risperidone and 9-hydroxyrisperidone are present in human breast milk. There are reports of sedation, failure to thrive, jitteriness, and extrapyramidal symptoms (tremors and abnormal muscle movements) in breast-fed infants exposed to risperidone. Risperidone has been detected in plasma in adult subjects up to 8 weeks after a single-dose administration of long-acting intramuscular risperidone (Risperdal Consta), and the clinical significance on the breast-fed infant is not known. There is no information regarding the effects of risperidone on milk production; antipsychotics may cause elevated prolactin levels and galactorrhea to varying degrees, and thus may interfere with proper lactation. Four case reports document the excretion of risperidone and 9-hydroxyrisperidone into breast milk; the milk/plasma ratio for all 4 women was less than 0.5 for both compounds. The calculated relative doses each infant received were 2.3%, 2.8%, 4.3%, and 4.7% of the maternal doses (weight adjusted). When the infant plasma samples were assayed, risperidone and 9-hydroxyrisperidone were not detectable. Each infant was thriving and no reported adverse effects were attributable to risperidone. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding. However, if an alternative antipsychotic is needed, other atypical agents such as olanzapine or quetiapine may be considered. Combination treatment with antipsychotics may increase the risk of adverse events.

    ADVERSE REACTIONS

    Severe

    tardive dyskinesia / Delayed / 0.1-5.3
    seizures / Delayed / 0-0.3
    suicidal ideation / Delayed / Incidence not known
    apnea / Delayed / Incidence not known
    akinesia / Delayed / Incidence not known
    neuroleptic malignant syndrome / Delayed / Incidence not known
    water intoxication / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    bradycardia / Rapid / Incidence not known
    atrial fibrillation / Early / Incidence not known
    cardiac arrest / Early / Incidence not known
    AV block / Early / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    diabetic ketoacidosis / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    ocular hypertension / Delayed / Incidence not known
    retinal thrombosis / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    pancreatitis / Delayed / Incidence not known
    stroke / Early / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    tissue necrosis / Early / Incidence not known

    Moderate

    pseudoparkinsonism / Delayed / 0-28.0
    constipation / Delayed / 5.0-17.0
    hyperglycemia / Delayed / 0.8-12.6
    akathisia / Delayed / 0-11.0
    urinary incontinence / Early / 1.0-7.0
    blurred vision / Early / 1.0-7.0
    hypercholesterolemia / Delayed / 4.3-6.3
    hyperlipidemia / Delayed / 2.5-6.3
    dystonic reaction / Delayed / 0-6.0
    hypertension / Early / 0-3.0
    sinus tachycardia / Rapid / 1.0-3.0
    cystitis / Delayed / 1.0-3.0
    hypertriglyceridemia / Delayed / 2.5-2.7
    orthostatic hypotension / Delayed / 0-2.0
    chest pain (unspecified) / Early / 2.0-2.0
    dyspnea / Early / 1.0-2.0
    anemia / Delayed / 0-1.0
    diabetes mellitus / Delayed / 0-0.4
    hyperprolactinemia / Delayed / 10.0
    mania / Early / Incidence not known
    depression / Delayed / Incidence not known
    confusion / Early / Incidence not known
    dysphonia / Delayed / Incidence not known
    teeth grinding (bruxism) / Delayed / Incidence not known
    dysarthria / Delayed / Incidence not known
    dyskinesia / Delayed / Incidence not known
    hyperthermia / Delayed / Incidence not known
    hyponatremia / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    peripheral edema / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    erythema / Early / Incidence not known
    eosinophilia / Delayed / Incidence not known
    atopic dermatitis / Delayed / Incidence not known
    hypotension / Rapid / Incidence not known
    bundle-branch block / Early / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hypoglycemia / Early / Incidence not known
    glycosuria / Early / Incidence not known
    gastritis / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    fecal incontinence / Early / Incidence not known
    dysphagia / Delayed / Incidence not known
    galactorrhea / Delayed / Incidence not known
    infertility / Delayed / Incidence not known
    precocious puberty / Delayed / Incidence not known
    urinary retention / Early / Incidence not known
    dysuria / Early / Incidence not known
    priapism / Early / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    ejaculation dysfunction / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    photophobia / Early / Incidence not known
    conjunctival hyperemia / Early / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    blepharospasm / Early / Incidence not known
    jaundice / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    wheezing / Rapid / Incidence not known
    ocular infection / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    hematoma / Early / Incidence not known
    skin ulcer / Delayed / Incidence not known

    Mild

    drowsiness / Early / 5.0-63.0
    appetite stimulation / Delayed / 1.7-44.0
    weight gain / Delayed / 8.0-32.6
    insomnia / Early / 0-32.0
    fatigue / Early / 1.0-31.0
    headache / Early / 0-21.0
    vomiting / Early / 10.0-20.0
    cough / Delayed / 2.0-17.0
    anxiety / Delayed / 0-16.0
    dizziness / Early / 3.0-16.0
    nausea / Early / 3.0-16.0
    abdominal pain / Early / 13.0-16.0
    fever / Early / 1.0-16.0
    rhinorrhea / Early / 12.0-12.0
    tremor / Early / 0-11.0
    hypersalivation / Early / 0-10.0
    dyspepsia / Early / 3.0-10.0
    xerostomia / Early / 0-10.0
    nasal congestion / Early / 4.0-10.0
    rhinitis / Early / 9.0-9.0
    rash / Early / 1.0-8.0
    diarrhea / Early / 1.0-8.0
    polydipsia / Early / 0-7.0
    nocturia / Early / 7.0-7.0
    back pain / Delayed / 1.0-6.8
    anorexia / Delayed / 6.0-6.0
    musculoskeletal pain / Early / 0-5.2
    weight loss / Delayed / 1.0-4.0
    amenorrhea / Delayed / 4.0-4.0
    arthralgia / Delayed / 2.0-4.0
    xerosis / Delayed / 0-3.0
    dental pain / Delayed / 1.0-3.0
    muscle cramps / Delayed / 0-2.6
    lethargy / Early / 2.0-2.0
    hypoesthesia / Delayed / 0-2.0
    asthenia / Delayed / 1.0-2.0
    epistaxis / Delayed / 0-2.0
    acne vulgaris / Delayed / 2.0-2.0
    syncope / Early / 1.0-2.0
    sinusitis / Delayed / 1.0-2.0
    injection site reaction / Rapid / 5.0
    agitation / Early / Incidence not known
    restlessness / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    somnambulism / Early / Incidence not known
    vertigo / Early / Incidence not known
    hypothermia / Delayed / Incidence not known
    malaise / Early / Incidence not known
    chills / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    maculopapular rash / Early / Incidence not known
    hyperkeratosis / Delayed / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known
    seborrhea / Delayed / Incidence not known
    night sweats / Early / Incidence not known
    skin discoloration / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    polyuria / Early / Incidence not known
    dysgeusia / Early / Incidence not known
    cheilitis / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    mastalgia / Delayed / Incidence not known
    menorrhagia / Delayed / Incidence not known
    oligomenorrhea / Delayed / Incidence not known
    vaginal discharge / Delayed / Incidence not known
    libido decrease / Delayed / Incidence not known
    breast enlargement / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    breast discharge / Delayed / Incidence not known
    increased urinary frequency / Early / Incidence not known
    orgasm dysfunction / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    ocular discharge / Delayed / Incidence not known
    xerophthalmia / Early / Incidence not known
    lacrimation / Early / Incidence not known
    blepharedema / Early / Incidence not known
    otalgia / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    flushing / Rapid / Incidence not known
    hyperventilation / Early / Incidence not known
    influenza / Delayed / Incidence not known
    infection / Delayed / Incidence not known
    pharyngitis / Delayed / Incidence not known
    ecchymosis / Delayed / Incidence not known
    skin irritation / Early / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation including risperidone. Prescribers need to weigh the potential benefits and risks of abarelix use in patients that are taking drugs that can cause QT prolongation.
    Acarbose: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Acebutolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of acebutolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving acebutolol concomitantly.
    Acetaminophen; Butalbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Acetaminophen; Butalbital; Caffeine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of dihydrocodeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known. (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Drugs that can cause CNS depression, including dichloralphenazone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness if used concomitantly with atypical antipsychotics.
    Acetaminophen; Diphenhydramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Acetaminophen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
    Acetaminophen; Pentazocine: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
    Acetaminophen; Propoxyphene: (Moderate) Concomitant use of propoxyphene with other CNS depressants, such as risperidone, can potentiate the effects of propoxyphene on respiratory depression and/or sedation.
    Acetaminophen; Tramadol: (Major) Concurrent use of tramadol and risperidone should be avoided if possible due to a possible increased risk of seizures. Seizures have been reported in patients receiving monotherapy with tramadol or antipsychotics at recommended doses. In addition, due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally-acting medications such as tramadol.
    Aclidinium; Formoterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Acrivastine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Albiglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Albuterol: (Minor) Use risperidone and short-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol; Ipratropium: (Minor) Use risperidone and short-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS or psyhcotropic activity. Use with caution.
    Alfentanil: (Moderate) Due to the sedative effects of risperidone, caution should be used when risperidone is given in combination with other centrally-acting medications including opiate agonists such as alfentanil.
    Alfuzosin: (Moderate) Use risperidone and alfuzosin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Alfuzosin may prolong the QT interval in a dose-dependent manner.
    Aliskiren; Amlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Alogliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alogliptin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alogliptin; Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alpha-glucosidase Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Alprazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Amifampridine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
    Amiodarone: (Major) Avoid coadministration of amiodarone and risperidone if possible due to the potential for an increased risk of QT prolongation and torsade de pointes (TdP). If coadministration is necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then closely monitor for QT interval prolongation and adjust the risperidone dosage as appropriate. Risperidone has been associated with a possible risk for QT prolongation and TdP; however, data are primarily in the overdose setting. Amiodarone is associated with a well-established risk of QT prolongation and TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
    Amitriptyline: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Amitriptyline; Chlordiazepoxide: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics. (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Amlodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Atorvastatin: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Benazepril: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Celecoxib: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Olmesartan: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Telmisartan: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Amlodipine; Valsartan: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Amobarbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Amoxapine: (Moderate) Use caution during co-administration of amoxapine and risperidone. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include risperidone.
    Angiotensin II receptor antagonists: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of angiotensin II receptor antagonists. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving angiotensin II receptor antagonists concomitantly.
    Angiotensin-converting enzyme inhibitors: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Apalutamide: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer like apalutamide. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting apalutamide. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of apalutamide to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing apalutamide, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating apalutamide in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of apalutamide in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Apomorphine: (Moderate) Use risperidone and apomorphine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, risperidone and apomorphine may reduce the effectiveness of each other due to opposing effects on dopamine. Apomorphine causes considerable somnolence, and concomitant administration of apomorphine and CNS depressants like risperidone could result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
    Arformoterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Aripiprazole: (Moderate) Use risperidone and aripiprazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    Arsenic Trioxide: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include arsenic trioxide.
    Artemether; Lumefantrine: (Major) Concomitant use of drugs with a possible risk of QT prolongation and torsade de pointes, including artemether; lumefantrine and risperidone, should be avoided if possible. Consider ECG monitoring if risperidone must be used with artemether; lumefantrine.
    Articaine; Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
    Asenapine: (Major) Avoid coadministration of risperidone and asenapine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Asenapine has also been associated with QT prolongation.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment. (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of dihydrocodeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
    Atazanavir: (Major) Avoid coadministration of atazanavir and risperidone when possible. Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of risperidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and risperidone.
    Atazanavir; Cobicistat: (Major) Avoid coadministration of atazanavir and risperidone when possible. Caution should be used in patients receiving atazanavir concurrently with drugs metabolized via CYP3A4 and known to cause QT prolongation. Atazanavir inhibits the CYP3A4 isoenzyme at clinically relevant concentrations, which may lead to increased serum concentrations of risperidone and an increased potential for QT prolongation or other adverse effects. Serious and/or life-threatening drug interactions could potentially occur between atazanavir and risperidone. (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
    Atenolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of atenolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving atenolol concomitantly.
    Atenolol; Chlorthalidone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of atenolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving atenolol concomitantly.
    Atomoxetine: (Moderate) Use risperidone and atomoxetine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with risperidone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Diphenoxylate: (Moderate) Concurrent administration of diphenoxylate/difenoxin with risperidone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Azithromycin: (Major) Avoid coadministration of azithromycin with risperidone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Barbiturates: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with risperidone. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Risperidone has also been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Belladonna; Opium: (Moderate) Additive CNS depression may occur if opiate agonists are used concomitantly with risperidone. The dose of one or both drugs should be reduced.
    Bendroflumethiazide; Nadolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of nadolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving nadolol concomitantly.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with risperidone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with risperidone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking risperidone, reduce initial dosage and titrate to clinical response. If risperidone is initiated a patient taking an opioid agonist, use a lower initial dose of risperidone and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Benzodiazepines: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Bepridil: (Severe) Bepridil administration is associated with a well-established risk of QT prolongation and torsades de pointes and is contraindicated in combination with other drugs that may also prolong the QT interval including risperidone.
    Betaxolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of betaxolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving betaxolol concomitantly.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Use risperidone and metronidazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Potential QT prolongation has been reported in limited case reports with metronidazole.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Use risperidone and metronidazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Potential QT prolongation has been reported in limited case reports with metronidazole.
    Bisoprolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of bisoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving bisoprolol concomitantly.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of bisoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving bisoprolol concomitantly.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering risperidone with boceprevir due to an increased potential for risperidone-related adverse events. If risperidone dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of risperidone. Risperidone is a substrate of the drug efflux transporter P-glycoprotein (PGP) and of the hepatic isoenzyme CYP3A4; boceprevir is an inhibitor of both the efflux protein and the isoenzyme. Coadministration may result in elevated risperidone plasma concentrations.
    Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as risperidone. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary.
    Brimonidine; Timolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of timolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving timolol concomitantly.
    Bromocriptine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
    Brompheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Brompheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Budesonide; Formoterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Bumetanide: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Buprenorphine: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of risperidone and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Risperidone has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of risperidone and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of risperidone and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Risperidone has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of risperidone and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
    Bupropion: (Major) Initiate risperidone at a reduced dose in patients receiving bupropion. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when bupropion is initiated or discontinued. An adjustment of the dose may be required. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Bupropion is a strong CYP2D6 inhibitor. Risperidone is a CYP2D6 substrate.
    Bupropion; Naltrexone: (Major) Initiate risperidone at a reduced dose in patients receiving bupropion. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when bupropion is initiated or discontinued. An adjustment of the dose may be required. Additionally, bupropion is associated with a dose-related increase in seizures; antipsychotics may increase this risk. Bupropion is a strong CYP2D6 inhibitor. Risperidone is a CYP2D6 substrate.
    Buspirone: (Moderate) The combination of buspirone and CNS depressants like the antipsychotics can increase the risk for drowsiness, sedation, and dizziness.
    Butabarbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Butorphanol: (Moderate) Concomitant use of butorphanol with risperidone can potentiate the effects of butorphanol on respiratory depression, CNS depression (e.g., dizziness, impaired mental function), and sedation. Use together with caution. If a centrally acting medication needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
    Cabergoline: (Moderate) Cabergoline should not be coadministered with risperidone due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of risperidone may diminish the prolactin-lowering ability of cabergoline while the dopamine agonist effects of cabergoline may exacerbate a psychotic disorder, reducing the effectiveness of antipsychotics such as risperidone.
    Calcium-channel blockers: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Canagliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Canagliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and atypical antipsychotics. CNS depressants can potentiate the effects of cannabidiol.
    Carbamazepine: (Moderate) Carbamazepine may decrease risperidone plasma concentrations. A risperidone dosage increase may need to be considered. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Carbamazepine is an enzyme-inducing medication. Additive sedation or other CNS effects are also possible. When oral risperidone is given with an enzyme inducer, slowly titrate the risperidone dose upwards; do not exceed twice the patient's usual dose. Upon discontinuation of the enzyme inducer, the risperidone dose should be re-evaluated and decreased if necessary. For the long-acting intramuscular risperidone injection (Risperdal Consta), adult patients should be closely monitored for the first 4 to 8 weeks after initiation of an enzyme inducer. A dose increase, or additional oral risperidone, may need to be considered. Upon discontinuation of the enzyme inducer, the dosage of Risperdal Consta should be re-evaluated and decreased if necessary. Patients may need to be placed on a lower dose of Risperdal Consta 2 to 4 weeks before the planned discontinuation of an enzyme inducer to adjust for the expected increase in risperidone plasma concentrations. For patients receiving 25 mg of Risperdal Consta, it is recommended to maintain the 25 mg dose upon discontinuation of the enzyme inducer unless clinical judgment warrants lowering the dose to 12.5 mg or interrupting risperidone treatment. The efficacy of the 12.5 mg dose has not been evaluated in clinical trials. When initiating carbamazepine in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of carbamazepine in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics. (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbidopa; Levodopa: (Moderate) Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of either agent during coadministration.
    Carbidopa; Levodopa; Entacapone: (Moderate) Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. Monitor for changes in movement, moods, or behaviors. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other antiparkison's agents than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, or diminished effectiveness of either agent during coadministration. (Moderate) Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of either agent during coadministration.
    Carbinoxamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Carbinoxamine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Cariprazine: (Moderate) The risk of adverse effects may be increased during concurrent use of cariprazine with other antipsychotics, such as risperidone. Similar to other antipsychotics, cariprazine administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. The incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, but the risk appears to be increased.
    Carteolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of carteolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving carteolol concomitantly.
    Carvedilol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of carvedilol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving carvedilol concomitantly.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and risperidone. Concurrent use may result in additive CNS depression.
    Central-acting adrenergic agents: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Ceritinib: (Major) Avoid coadministration of ceritinib with risperidone if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Reports of QT prolongation and torsade de pointes (TdP) during risperidone therapy are also noted by the manufacturer, primarily in the overdose setting.
    Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Cetrorelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs including cetrorelix.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Chlorcyclizine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Chlordiazepoxide: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Chlordiazepoxide; Clidinium: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Chloroquine: (Major) Avoid coadministration of chloroquine with risperidone due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Chlorpheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Dextromethorphan: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of dihydrocodeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of dihydrocodeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as chlorpheniramine. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Chlorpromazine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include chlorpromazine. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Cinacalcet: (Major) Initiate risperidone at a reduced dose in patients receiving cinacalcet as increased plasma concentrations of risperidone and toxicity may occur. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when cinacalcet is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; cinacalcet is a potent CYP2D6 inhibitor.
    Ciprofloxacin: (Moderate) Use risperidone and ciprofloxacin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Rare cases of QT prolongation TdP have been reported with ciprofloxacin during postmarketing surveillance.
    Cisapride: (Severe) Risperidone has been associated with a possible risk for QT prolongation and torsade de pointes (TdP); however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Because of the potential for TdP, use of cisapride with risperidone is contraindicated.
    Citalopram: (Major) Because both citalopram and risperidone are associated with a possible risk for QT prolongation and torsade de pointes (TdP), caution is advisable during concurrent use. Citalopram causes dose-dependent QT interval prolongation and risperidone is associated with a risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended.
    Clarithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with risperidone. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Clarithromycin is associated with an established risk for QT prolongation and TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Clemastine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Clevidipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Clobazam: (Moderate) Benzodiazepines such as clobazam should be combined cautiously with antipsychotics because of the potential for additive CNS depressant effects, and reduced effectiveness of clobazam as an anticonvulsant due to the possible lowering of the seizure threshold by antipsychotics.
    Clofazimine: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with risperidone. QT prolongation and torsade de pointes (TdP) have been reported in patients receiving clofazimine in combination with QT prolonging medications. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Clomipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Clonazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Clorazepate: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Clozapine: (Moderate) Because both clozapine and risperidone have a possible risk for QT prolongation and/or torsade de pointes (TdP), caution is advisable during concurrent use. Reports of QT prolongation and TdP during risperidone therapy are noted primarily in the overdosage setting. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death. If coadministration is required, the patient's underlying medical conditions and additional potential risk factors should be considered. Patients with known risk factors for cardiac disease or arrhythmia should be closely monitored. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, or seizures. Chronic administration of clozapine and risperidone may decrease the clearance of risperidone.
    Cobicistat: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
    Cocaine: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsades de pointes and should be used cautiously in combination with other drugs that also prolong the QT interval, including local anesthetics.
    Codeine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Codeine; Promethazine: (Moderate) Concomitant use of codeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of codeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of codeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    COMT inhibitors: (Moderate) Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. Monitor for changes in movement, moods, or behaviors. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other antiparkison's agents than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, or diminished effectiveness of either agent during coadministration.
    Crizotinib: (Major) Avoid coadministration of crizotinib with risperidone due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Risperidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting.
    Cyclizine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Cyproheptadine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Dacomitinib: (Major) Initiate risperidone at a reduced dose in patients receiving dacomitinib as increased plasma concentrations of risperidone and toxicity may occur. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when dacomitinib is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; dacomitinib is a strong CYP2D6 inhibitor.
    Dantrolene: (Moderate) Simultaneous use of skeletal muscle relaxants and other CNS depressants, such as antipsychotics, can increase CNS depression.
    Dapagliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Dapagliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Dapagliflozin; Saxagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Darunavir: (Major) Decreased risperidone doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the risperidone, resulting in increased risperidone concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
    Darunavir; Cobicistat: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required. (Major) Decreased risperidone doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the risperidone, resulting in increased risperidone concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required. (Major) Decreased risperidone doses may be required when coadministered with darunavir/ritonavir. Darunavir/ritonavir is expected to decrease the hepatic metabolism of the risperidone, resulting in increased risperidone concentrations. If coadministration of these drugs is warranted, do so with caution and careful monitoring.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
    Dasatinib: (Moderate) Use dasatinib with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Degarelix: (Major) Avoid coadministration of degarelix with risperidone due to the risk of reduced efficacy of degarelix; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; degarelix is a GnRH analog. Additionally, risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
    Desipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Desvenlafaxine: (Major) Coadministration of risperidone, a CYP2D6 substrate, and desvenlafaxine, a CYP2D6 inhibitor, may increase plasma concentrations of risperidone. Clinical studies have shown desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at doses less than 100 mg/day; hence, per desvenlafaxine product labeling, CYP2D6 substrates can be dosed at the original level when desvenlafaxine doses are 100 mg or less or when desvenlafaxine is discontinued. For desvenlafaxine doses more than 400 mg, product labeling recommends to reduce the risperidone dose by one-half.
    Deutetrabenazine: (Moderate) Assess the QTc interval before and after increasing the dosage of either medication for patients taking a deutetrabenazine dosage more than 24 mg/day with risperidone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, monitor for excessive hypotension and sedation during coadministration as risperidone can potentiate the effects of CNS depressants. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Clinically relevant QTc prolongation may occur with deutetrabenazine.
    Dexchlorpheniramine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Dexmethylphenidate: (Moderate) Atypical antipsychotics and dexmethylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Dexmethylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of dexmethylphenidate.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Dextromethorphan; Promethazine: (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Dextromethorphan; Quinidine: (Severe) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include risperidone.
    Diazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with other central nervous system (CNS) depressants, such as risperidone, can potentiate the effects of dihydrocodeine and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of dihydrocodeine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of dihydrocodeine and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Diltiazem: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Dimenhydrinate: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Diphenhydramine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone. (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Diphenhydramine; Ibuprofen: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Diphenhydramine; Naproxen: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Diphenhydramine; Phenylephrine: (Moderate) Due to the primary CNS effects of risperidone, caution is advisable when risperidone is given with other centrally acting medications including sedating H1-blockers such as diphenhydramine. This combination is commonly used in clinical practice; however, additive drowsiness or other CNS effects may occur. Patients should be informed of the risk of driving or performing other tasks requiring mental alertness until the effects of these medicines are known.
    Disopyramide: (Major) Risperidone should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
    Dofetilide: (Major) Coadministration of dofetilide and risperidone is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Dolasetron: (Moderate) Administer dolasetron with caution in combination with risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Donepezil: (Moderate) Use donepezil with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with risperidone as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Dopamine: (Minor) The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone.
    Dorzolamide; Timolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of timolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving timolol concomitantly.
    Doxazosin: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Doxepin: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Doxylamine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Doxylamine; Pyridoxine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
    Dronabinol: (Moderate) Drugs that can cause CNS depression such as dronabinol, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
    Dronedarone: (Severe) Concomitant use of dronedarone with risperidone is contraindicated due to the potential risk of QT prolongation and torsade de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Risperidone has been associated with a possible risk of QT prolongation and/or TdP, primarily in the overdose setting. In addition, dronedarone is an inhibitor of CYP2D6. Risperidone is a substrate for CYP2D6. Concomitant use of dronedarone with risperidone may increase risperidone concentration and further increase the risk for adverse cardiac effects.
    Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
    Dulaglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Efavirenz: (Major) Coadministration of efavirenz and risperidone may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, efavirenz may induce the CYP3A4 metabolism of risperidone, potentially reducing the efficacy of risperidone by decreasing its systemic exposure.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of efavirenz and risperidone may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, efavirenz may induce the CYP3A4 metabolism of risperidone, potentially reducing the efficacy of risperidone by decreasing its systemic exposure.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and risperidone may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. In addition, efavirenz may induce the CYP3A4 metabolism of risperidone, potentially reducing the efficacy of risperidone by decreasing its systemic exposure.
    Elbasvir; Grazoprevir: (Moderate) Administering risperidone with elbasvir; grazoprevir may result in elevated risperidone plasma concentrations. Risperidone is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Eliglustat: (Moderate) Use risperidone and eliglustat together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of risperidone, a CYP2D6 substrate, and cobicistat, a potent CYP2D6 inhibitor, may increase plasma concentrations of risperidone. When oral risperidone is given with a potent CYP2D6 inhibitor, the dose of risperidone should not exceed 8 mg/day PO in adults. When initiating therapy, titrate risperidone slowly. Upon discontinuation of the CYP2D6 inhibitor, the risperidone dose should be re-evaluated and increased if necessary. For the long-acting risperidone injection, the current adult dosage should be closely monitored when a potent CYP2D6 inhibitor is initiated or discontinued. An adjustment of the dose may be required.
    Empagliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Empagliflozin; Linagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Empagliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Use risperidone and rilpivirine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Enalapril; Felodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Encainide: (Major) Since risperidone has a possible risk for QT prolongation and torsade de pointes, caution is advisable during concurrent use of other agents also known to have these effects, including encainide.
    Encorafenib: (Major) Avoid coadministration of encorafenib and risperidone due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy have been reported, primarily in the overdosage setting.
    Entacapone: (Moderate) Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. Monitor for changes in movement, moods, or behaviors. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other antiparkison's agents than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, or diminished effectiveness of either agent during coadministration.
    Entrectinib: (Major) Avoid coadministration of entrectinib with risperidone due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Enzalutamide: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer like enzalutamide. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting enzalutamide. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of enzalutamide to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing enzalutamide, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating enzalutamide in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of enzalutamide in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Epinephrine: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed.
    Eplerenone: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Epoprostenol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Eribulin: (Moderate) Monitor ECG if risperidone is coadministered with eribulin due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Eribulin has also been associated with QT prolongation.
    Ertugliflozin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ertugliflozin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ertugliflozin; Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Erythromycin: (Major) Use erythromycin and risperidone together with caution since there is an increased risk for QT prolongation and torsade de pointes (TdP). Monitor patients with known risk factors for cardiac disease or arrhythmia closely during coadministration. Erythromycin has been associated with QT prolongation and TdP. Risperidone has also been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Dose adjustment is not recommended for risperidone when co-administered with erythromycin, as pharmacokinetic studies did not indicate a significant effect of erythromycin on risperidone pharmacokinetics, including risperidone exposure (AUC) and maximum concentrations (Cmax).
    Erythromycin; Sulfisoxazole: (Major) Use erythromycin and risperidone together with caution since there is an increased risk for QT prolongation and torsade de pointes (TdP). Monitor patients with known risk factors for cardiac disease or arrhythmia closely during coadministration. Erythromycin has been associated with QT prolongation and TdP. Risperidone has also been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Dose adjustment is not recommended for risperidone when co-administered with erythromycin, as pharmacokinetic studies did not indicate a significant effect of erythromycin on risperidone pharmacokinetics, including risperidone exposure (AUC) and maximum concentrations (Cmax).
    Escitalopram: (Moderate) Use risperidone and escitalopram together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Escitalopram has also been associated with a risk of QT prolongation and TdP.
    Esketamine: (Major) Closely monitor patients receiving esketamine and risperidone for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Esmolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of esmolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving esmolol concomitantly.
    Estazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as antipsychotics, to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Antipsychotics with a higher incidence of sedation, such as olanzapine, clozapine, quetiapine, lurasidone, chlorpromazine, and thioridazine, are more likely to interact with eszopiclone. In one evaluation, concurrent use of eszopiclone and olanzapine reduced psychomotor function as measured by the Digit Symbol Substitution Test (DSST).
    Ethacrynic Acid: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Ethanol: (Moderate) Alcohol may potentiate the CNS effects of the atypical antipsychotics, which have the potential to cause increased sedation, or to impair judgment, thinking, or motor skills. Patients should be appropriately cautioned.
    Ethotoin: (Major) Because antipsychotics such as risperidone can lower the seizure threshold, the effectiveness of ethotoin as an anticonvulsant may be reduced. In addition, inducers of CYP3A4, such as ethotoin, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials.
    Exenatide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Ezogabine: (Moderate) Use risperidone and ezogabine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Ezogabine has also been associated with QT prolongation.
    Felodipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and risperidone. Concurrent use may result in additive CNS depression.
    Fentanyl: (Moderate) Concomitant use of fentanyl with other central nervous system (CNS) depressants such as risperidone can potentiate the effects of fentanyl and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of fentanyl in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If these agents are used together, a reduced dosage of fentanyl and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Fingolimod: (Moderate) Monitor ECG continuously overnight in a medical facility after the first fingolimod dose if risperidone is coadministered due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering risperidone with flecainide. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is recommended. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdosage setting. Flecainide, a Class IC antiarrhythmic, increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
    Fluconazole: (Moderate) Use fluconazole and risperidone together with caution since there is an increased risk for QT prolongation and torsade de pointes (TdP). Monitor patients with known risk factors for cardiac disease or arrhythmia closely during coadministration. Fluconazole has been associated with QT prolongation and rare cases of TdP. Risperidone has also been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Fluoxetine: (Major) Initiate risperidone at a reduced dose in patients receiving fluoxetine as increased plasma concentrations of risperidone and toxicity may occur; additive QT prolongation is also possible. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when fluoxetine is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; fluoxetine is a potent CYP2D6 inhibitor. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation and TdP have also been reported in patients treated with fluoxetine.
    Fluoxetine; Olanzapine: (Major) Initiate risperidone at a reduced dose in patients receiving fluoxetine as increased plasma concentrations of risperidone and toxicity may occur; additive QT prolongation is also possible. Do not exceed 8 mg PO per day of risperidone if these drugs are coadministered. For the long-acting risperidone injection, the current adult dosage should be closely monitored when fluoxetine is initiated or discontinued. An adjustment of the dose may be required. Risperidone is a CYP2D6 substrate; fluoxetine is a potent CYP2D6 inhibitor. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. QT prolongation and TdP have also been reported in patients treated with fluoxetine. (Moderate) Use risperidone and olanzapine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
    Fluphenazine: (Moderate) Use risperidone and fluphenazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Flurazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Fluticasone; Salmeterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluvoxamine: (Moderate) Use risperidone and fluvoxamine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
    Food: (Major) It is recommended that patients avoid the use of marijuana, by any route, if they are treated for a psychiatric history, including psychosis and bipolar disorder, as the cannabinoids (the psychoactive ingredients, such as THC) in marijuana can produce psychotoxic effects and may exacerbate psychiatric disorders. A high frequency of use and use of products with high-potency of THC are potential risk factors for psychiatric effects. Additionally, additive CNS effects, such as sedation or CNS depression are possible. Clinical studies suggest that cannabis use may reduce the efficacy of some antipsychotic drugs. In addition, several cannabinoids in marijuana appear to influence the activity of CYP enzymes and P-glycoprotein, which may alter the concentrations of antipsychotics and influence either safety or efficacy, For example, the smoking of marijuana influences the metabolism of some medications in a manner similar to tobacco by inducing CYP1A2.
    Formoterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Formoterol; Mometasone: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fosamprenavir: (Major) Concomitant use of risperidone and fosamprenavir may result in altered risperidone plasma concentrations. Risperidone is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is an inducer of P-gp and a potent inhibitor and moderate inducer of CYP3A4.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as risperidone. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Risperidone has also been associated with a possible risk for QT prolongation and TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosphenytoin: (Major) Because antipsychotics such as risperidone can lower the seizure threshold, the effectiveness of fosphenytoin may be reduced. In addition, potent inducers of CYP3A4, such as fosphenytoin, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Fostemsavir: (Moderate) Use risperidone and fostemsavir together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
    Furosemide: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of antihypertensive agents. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly. Furthermore, two of four placebo-controlled trials showed that elderly patients with dementia-related psychosis receiving the combination of risperidone and furosemide had a higher incidence of mortality than those receiving either agent alone. The mechanism for this adverse association is unknown. Caution should be exercised when the combined use of risperidone and furosemide is necessary in those with dementia-related psychosis.
    Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and risperidone. Concomitant use of gabapentin with risperidone may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Ganirelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to ganirelix, a gonadotropin-releasing hormone (GnRH) analog.
    Gemifloxacin: (Moderate) Use risperidone and gemifloxacin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and risperidone together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Gilteritinib: (Moderate) Use caution and closely monitor for additive QT prolongation if concurrent use of gilteritinib and risperidone is necessary. Gilteritinib has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) during risperidone therapy have primarily occurred in the overdosage setting.
    Glasdegib: (Major) Avoid coadministration of glasdegib with risperidone due to the potential for additive QT prolongation. If coadministration cannot be avoided, consider the patient's underlying disease state(s) and additional potential risk factors. Monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Glimepiride; Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Glimepiride; Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Glipizide; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Glyburide; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Glycopyrrolate; Formoterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Goserelin: (Major) Avoid coadministration of goserelin with risperidone due to the risk of reduced efficacy of goserelin; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
    Granisetron: (Moderate) Use risperidone and granisetron together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Guaifenesin; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Halofantrine: (Severe) Halofantrine is considered to have a well-established risk for QT prolongation and torsades de pointes and should be avoided in patients receiving drugs which may induce QT prolongation including risperidone.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with risperidone. Halogenated anesthetics can prolong the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors.
    Haloperidol: (Major) Caution is advisable when coadministering medications that have a possible risk of QT prolongation and torsade de pointes (TdP), including risperidone and haloperidol. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation than with routine oral dosing. Coadministration of haloperidol with risperidone may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Histrelin: (Major) Avoid coadministration of histrelin with risperidone due to the risk of reduced efficacy of histrelin; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
    Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of metoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving metoprolol concomitantly.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of propranolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving propranolol concomitantly.
    Hydrocodone: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Hydrocodone; Phenylephrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of hydrocodone with other CNS depressants may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use of hydrocodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Drugs that may cause additive CNS effects include risperidone.
    Hydromorphone: (Moderate) Concomitant use of hydromorphone with other central nervous system (CNS) depressants can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma. Examples of drugs associated with CNS depression include risperidone. Prior to concurrent use of hydromorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If hydromorphone is used concurrently with a CNS depressant, a reduced dosage of hydromorphone and/or the CNS depressant is recommended; start with one-third to one-half of the estimated hydromorphone starting dose when using hydromorphone extended-release tablets. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Hydroxychloroquine: (Major) Avoid coadministration of risperidone and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de points (TdP), primarily in the overdose setting.
    Hydroxyzine: (Moderate) Use risperidone and hydroxyzine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
    Ibuprofen; Oxycodone: (Moderate) Concomitant use of oxycodone with other CNS depressants, such as risperidone, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking risperidone, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxycodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also, consider using a lower risperidone dose. Monitor patients for sedation and respiratory depression.
    Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as risperidone. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Imipramine: (Moderate) Use risperidone and tricyclic antidepressants together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Additionally, coadministration may result in additive CNS effects. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Tricyclic antidepressants share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
    Incretin Mimetics: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Indacaterol: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with risperidone due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Insulin Degludec; Liraglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Insulin Glargine; Lixisenatide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Insulins: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Isocarboxazid: (Moderate) Due to the potential for additive sedative and cardiovascular effects (e.g., hypotension), MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp like rifampin. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating rifampin in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of rifampin in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Isoniazid, INH; Rifampin: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp like rifampin. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating rifampin in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of rifampin in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Isradipine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Itraconazole: (Moderate) Use risperidone and itraconazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Itraconazole has also been associated with prolongation of the QT interval.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with risperidone due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Ketoconazole: (Moderate) Use risperidone and ketoconazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Ketoconazole has also been associated with prolongation of the QT interval.
    Labetalol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of labetalol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving labetalol concomitantly.
    Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with risperidone. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and risperidone. Concurrent use may result in additive CNS depression.
    Lefamulin: (Major) Avoid coadministration of lefamulin with risperidone as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with risperidone due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Risperidone has also been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting.
    Leuprolide: (Major) Avoid coadministration of leuprolide with risperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with risperidone due to the risk of reduced efficacy of leuprolide; QT prolongation may also occur. Risperidone can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
    Levalbuterol: (Minor) Use risperidone and short-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with atypical antipsychotics should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
    Levodopa: (Moderate) Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of either agent during coadministration.
    Levofloxacin: (Moderate) Use risperidone and levofloxacin together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Levofloxacin has been associated with a risk of QT prolongation and TdP. Although extremely rare, torsade de pointes has been reported during postmarketing surveillance of levofloxacin.
    Levomethadyl: (Severe) Levomethadyl is associated with an established risk of QT prolongation and/or torsades de pointes and is contraindicated in combination with other agents that may prolong the QT interval, such as risperidone.
    Levorphanol: (Moderate) Concomitant use of levorphanol with other CNS depressants such as risperidone can potentiate the effects of levorphanol on respiration, blood pressure, and alertness. Severe hypotension, respiratory depression, profound sedation, or coma may occur. Prior to concurrent use of levorphanol in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. When concomitant treatment with levorphanol with another CNS depressant is necessary, reduce the dose of 1 or both drugs. The initial dose of levorphanol should be reduced by approximately 50% or more when levorphanol is used with another drug that may depress respiration.
    Linagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Linagliptin; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Liraglutide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Lithium: (Moderate) Use risperidone and lithium together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, it is advisable to monitor patients for neurotoxicity. Neuroleptic malignant syndrome (NMS) has been observed occasionally during concurrent use of lithium and either atypical or conventional antipsychotics. Additive extrapyramidal effects have also been noted. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Lithium has also been associated with QT prolongation.
    Lixisenatide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with risperidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Additionally, monitor for excessive hypotension and sedation during coadministration as lofexidine can potentiate the effects of CNS depressants. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
    Lomefloxacin: (Moderate) Quinolones have been associated with QT prolongation and in rare cases, torsades de pointes and should be used with caution in patients receiving drugs that prolong the QT interval, such as risperidone.
    Long-acting beta-agonists: (Moderate) Use risperidone and long-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Loperamide: (Moderate) Use risperidone and loperamide together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
    Loperamide; Simethicone: (Moderate) Use risperidone and loperamide together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, TdP, and cardiac arrest.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with risperidone due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the overdose setting. (Moderate) Ritonavir may increase risperidone exposure; use together with caution and monitor for adverse effects of risperidone, including QT prolongation or other risperidone side effects. A decreased dosage of risperidone may be required. Risperidone is primarily metabolized by CYP2D6 and is also partially metabolized by CYP3A4; ritonavir inhibits both CYP2D6 and CYP3A4.
    Lorazepam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Loxapine: (Major) Caution is advisable during concurrent use of loxapine and risperidone. Loxapine use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and risperidone. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Lumacaftor; Ivacaftor: (Major) Potent inducers of CYP3A4, such as lumacaftor, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed, up to double the patient's usual dose, during use of a 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. When planning discontinuation of a CYP3A4 inducer, a lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation to adjust for the expected increase in concentrations of risperidone and its active metabolite. For patients treated with Risperdal Consta 25 mg and discontinuing an inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials.
    Lumacaftor; Ivacaftor: (Major) Potent inducers of CYP3A4, such as lumacaftor, may decrease plasma concentrations of risperidone and its active metabolite. Therefore, the manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed, up to double the patient's usual dose, during use of a 3A4 inducer. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting an inducer. When planning discontinuation of a CYP3A4 inducer, a lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation to adjust for the expected increase in concentrations of risperidone and its active metabolite. For patients treated with Risperdal Consta 25 mg and discontinuing an inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials.
    Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and risperidone, may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from antipsychotic combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
    Lurasidone: (Moderate) Co-administration of risperidone with lurasidone may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as risperidone. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Risperidone has been associated with a possible risk for QT prolongation and torsade de pointes. Reports of QT prolongation and torsade de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Maprotiline: (Moderate) Use risperidone and maprotiline together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
    Mecamylamine: (Moderate) Risperidone has been associated with orthostatic hypotension and may enhance the hypotensive effects of antihypertensive agents. Clinically significant hypotension has been observed with concomitant use of risperidone and antihypertensive medications. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving antihypertensive agents concomitantly.
    Meclizine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including meclizine. Additive drowsiness or other CNS effects may occur.
    Mefloquine: (Moderate) Use risperidone and mefloquine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
    Meglitinides: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Meperidine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including meperidine. Hypotension, respiratory and/or CNS depression can be additive if meperidine is used concomitantly with risperidone.
    Meperidine; Promethazine: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including meperidine. Hypotension, respiratory and/or CNS depression can be additive if meperidine is used concomitantly with risperidone. (Moderate) Use risperidone and promethazine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). In addition, coadministration may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Mephobarbital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including antipsychotics.
    Mesoridazine: (Severe) Due to the risk of additive QT prolongation and potential for serious arrhythmias, the concurrent use of risperidone and mesoridazine is considered contraindicated. Mesoridazine has an established risk of QT prolongation and torsade de pointes (TdP) and risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP), primarily in the setting of overdose.
    Metaproterenol: (Minor) Use risperidone and short-acting beta-agonists together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Saxagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Metformin; Sitagliptin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Methadone: (Major) Methadone has a known risk of QT prolongation and torsade de pointes (TdP) and a careful assessment of risks versus benefits should be performed before coadministration with drugs having a possible risk of QT prolongation and TdP such as risperidone. Methadone is particularly associated with an increased risk for QT prolongation and TdP at higher doses (e.g., 400 mg/day in adults). Concomitant use of CNS depressants, such as risperidone and methadone, can lead to additive CNS depression, hypotension, or coma. Prior to the use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, the patient's overall response to treatment, and the patient's use of alcohol or illicit drugs. In opioid-naive adults, initiate methadone at a dose of 2.5 mg every 12 hours in patients receiving other CNS depressants. Also consider using a lower dose of the CNS depressant.
    Methohexital: (Major) Potent inducers of CYP3A4, such as barbiturates, may decrease plasma concentrations of risperidone and its active metabolite. In addition, risperidone may decrease anticonvulsant efficacy by lowering the seizure threshold. Additive sedation or other CNS effects are also possible. The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer and inducer of P-gp. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting a strong CYP3A4 inducer. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of the inducer to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing the inducer, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating a strong CYP3A4 inducer in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of a strong CYP3A4 inducer in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Methylphenidate: (Moderate) Atypical antipsychotics and methylphenidate may interact pharmacodynamically to diminish the therapeutic effects of either agent through opposing effects on dopamine. Methylphenidate blocks central dopamine reuptake, which has the potential to exacerbate psychosis, and antipsychotics, which are central dopamine antagonists, may diminish the effectiveness of methylphenidate.
    Metoclopramide: (Severe) Concomitant use of metoclopramide and antipsychotics is contraindicated by the manufacturer of metoclopramide as the risk of extrapyramidal effects may be increased. Both metoclopramide and antipsychotics antagonize dopamine receptors, which can increase the risk of extrapyramidal effects, including tardive dyskinesia or other dystonic reactions. Additionally, because both antipsychotics and metoclopramide can cause sedation, seizures, or increased prolactin levels, it is possible that the risk of these effects may be increased during concurrent use.
    Metoprolol: (Moderate) Risperidone may induce orthostatic hypotension and thus enhance the hypotensive effects of metoprolol. Lower initial doses or slower dose titration of risperidone may be necessary in patients receiving metoprolol concomitantly.
    Metronidazole: (Moderate) Use risperidone and metronidazole together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Potential QT prolongation has been reported in limited case reports with metronidazole.
    Midazolam: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics.
    Midostaurin: (Major) The concomitant use of midostaurin and risperidone may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram (ECG) monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Pooled data from controlled trials indicate there are no statistically significant differences in mean changes from baseline in ECG parameters including QT, QTc, and PR intervals when risperidone is compared to placebo. However, post-marketing reports of overdose indicate that QT prolongation and torsade de pointes have occurred.
    Mifepristone: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and risperidone should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Risperidone has been associated with a possible risk for QT prolongation and TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
    Miglitol: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
    Mirtazapine: (Moderate) Use risperidone and mirtazapine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. TdP has been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation.
    Mitotane: (Major) The manufacturer of oral risperidone recommends a slow upward titration of the risperidone dose as needed up to double the patient's usual dose during use of a strong 3A4 inducer like mitotane. When using Risperdal Consta, the patient will require close monitoring for 4 to 8 weeks when starting mitotane. A lower dose of Risperdal Consta may be prescribed between 2 to 4 weeks before the planned discontinuation of mitotane to adjust for the expected increase in plasma concentrations of risperidone and its active metabolite. For patients treated with the recommended dose of Risperdal Consta 25 mg and discontinuing mitotane, it is recommended to continue the 25 mg dose unless a reduction to 12.5 mg or discontinuation of treatment is indicated. The efficacy of the 12.5 mg dose has not been studied in clinical trials. When initiating mitotane in patients receiving the long-acting subcutaneous risperidone injection (Perseris), close monitoring for 4 to 8 weeks is recommended. In patients receiving 90 mg of Perseris, consider increasing the dose to 120 mg. In patients receiving 120 mg of Perseris, additional oral risperidone may need to be considered. Upon discontinuation of mitotane in patients receiving 120 mg of Perseris, the dose of Perseris and additional use of oral risperidone should be re-evaluated and adjusted if necessary. For patients receiving 90 mg of Perseris, the current dose of Perseris may be maintained unless clinical circumstances require interruption of Perseris treatment.
    Molindone: (Major) Co-administration of risperidone with molindone may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
    Monoamine oxidase inhibitors: (Moderate) Due to the potential for additive sedative and cardiovascular effects (e.g., hypotension), MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Morphine: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include risperidone. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
    Morphine; Naltrexone: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include risperidone. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression.
    Moxifloxacin: (Major) Concurrent use of risperidone and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Moxifloxacin has been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. Risperidone has also been associated with a possible risk for QT prolongation and/or TdP; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
    Nabilone: (Moderate) Drugs that can cause CNS depressi