Version October 2024
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Risperidone is not approved for the treatment of patients with dementia-related psychosis.
Dosage guidance:
Dosing: Although manufacturer's labeling for the oral tablet includes a maximum dose of up to 16 mg/day, doses >8 mg/day are generally not recommended (Ref).
Agitation/Aggression (severe, acute) associated with psychiatric disorders (eg, schizophrenia, bipolar disorder), substance intoxication, or other organic causes (alternative agent) (off-label use) :
Note: Antipsychotics are appropriate when psychosis is suspected to be the primary cause of agitation/aggression (Ref). Other agents are used preferentially in some intoxications (eg, stimulants) or alcohol withdrawal (Ref). Depending on presentation, may combine with a benzodiazepine.
Oral: Initial: 1 to 2 mg; may repeat every 2 hours to a maximum daily dose of 6 mg (Ref).
Agitation/Aggression and psychosis associated with dementia, severe or refractory (alternative agent) (off-label use):
Note: For short-term use while addressing underlying causes of severe symptoms (Ref). In patients without a clinically significant response after an adequate trial (eg, up to 4 weeks), taper and withdraw therapy. Only continue in patients with demonstrated benefit; attempt to taper and withdraw at regular intervals (eg, ≤4 months). Patients with dementia with Lewy bodies are at increased risk for severe adverse reactions; caution is required even with low doses (Ref).
Oral: Initial: 0.5 mg/day in 2 divided doses; may increase dose based on response and tolerability in increments of 0.5 mg/day at intervals ≥2 days up to 1 mg/day (Ref).
Bipolar disorder:
Acute mania or acute episodes with mixed features (labeled use) or acute hypomania (off-label use) (monotherapy or adjunctive therapy):
Oral: Initial: 1 to 3 mg/day in 1 or 2 divided doses; may adjust dose based on response and tolerability in increments of 1 mg/day at intervals ≥24 hours to a usual dose of 4 to 6 mg/day; in general, assess full effect for ≥1 week before further advancing up to 8 mg/day (usual maximum) (Ref).
Maintenance treatment (monotherapy or as adjunct to antimanic therapy):
Oral: Continue dose and combination regimen that was used to achieve control of the acute episode (Ref)
IM ER suspension (alternative route):
Note: Establish tolerability using oral risperidone before first injection. Due to delayed onset of the first ER IM injection, an oral antipsychotic at an effective dose is overlapped for the first 3 weeks for Risperdal Consta and for the first week for Rykindo.
Initial: 25 mg every 2 weeks; in patients with a history of treatment-refractory illness or requiring high doses of antipsychotics, some experts initiate at 37.5 mg (Ref). If insufficient response, may increase dose in increments of 12.5 mg no sooner than every 4 weeks to a maximum dose of 50 mg every 2 weeks (Ref).
Conversion between oral and IM ER suspension: The manufacturer's labeling does not provide dose conversions to IM ER suspension based on current oral dose. Some experts recommend converting to IM ER suspension at the usual starting dose and titrating according to response (Ref). Some experts recommend the following conversions from oral to IM ER suspension (Ref):
≤3 mg/day oral = 25 mg IM ER suspension every 2 weeks.
>3 to ≤5 mg/day oral = 37.5 mg IM ER suspension every 2 weeks.
>5 mg/day oral = 50 mg IM ER suspension every 2 weeks.
Conversion between Risperdal Consta IM ER suspension and Rykindo IM ER suspension: Continue same dose, with first dose of Rykindo administered 4 to 5 weeks after last injection of Risperdal Consta. No oral overlap needed.
Delusional disorder (alternative agent) (off-label use):
Oral: Initial: 1 to 2 mg/day in 1 or 2 divided doses; may increase dose based on response and tolerability in increments of 1 mg/day every 2 weeks; usual dose is ~5 mg/day in 2 divided doses; maximum dose: 8 mg/day (Ref).
Delusional infestation (delusional parasitosis) (off-label use):
Oral: Initial: 0.5 mg/day in 1 or 2 divided doses; may increase dose based on response and tolerability gradually (ie, weekly) up to 2 to 4 mg/day in 1 or 2 divided doses. Doses up to 8 mg/day may be necessary in some patients (Ref). After achieving adequate response, maintain for ≥1 to 12 months before attempting to taper (Ref).
Huntington disease–associated chorea, moderate to severe (alternative agent) (off-label use):
Oral: Initial: 0.5 to 2 mg/day in 1 or 2 divided doses; may increase dose based on response and tolerability in increments of 1 mg/day every week; some patients may require doses up to 10 mg/day (Ref).
Major depressive disorder (unipolar), treatment resistant (adjunctive therapy with antidepressant) (off-label use):
Oral: Initial: 0.25 to 0.5 mg/day; may increase dose based on response and tolerability in increments of 0.25 to 1 mg/day every 3 to 7 days up to 3 mg/day. Usual effective dose: 1 to 1.5 mg/day (Ref).
Obsessive-compulsive disorder, treatment resistant (augmentation to antidepressants) (off-label use):
Oral: Initial: 0.25 to 0.5 mg/day; may increase dose based on response and tolerability in increments of 0.5 to 1 mg/day every 3 to 7 days; usual dose: 0.5 to 2 mg/day; doses up to 3 mg/day may be needed for optimal response (Ref).
Schizophrenia:
Oral: Initial: 1 to 2 mg/day in 1 to 2 divided doses; may increase by 1 to 2 mg/day at intervals ≥24 hours to usual dosage range of 2 to 6 mg/day. In general, assess full effect for ≥1 week before further advancing, if needed, to 6 to 8 mg/day (usual maximum). Note: Doses up to 16 mg/day have been evaluated in clinical trials and are approved according to manufacturer's labeling but are associated with increased adverse effects and generally are not recommended (Ref).
IM ER suspension:
Note: Establish tolerability using oral risperidone before first injection. Due to delayed onset of the first IM ER suspension injection, an oral antipsychotic at an effective dose is overlapped for the first 3 weeks for Risperdal Consta and for the first week for Rykindo.
Initial: 25 mg every 2 weeks; may increase dose based on response and tolerability in increments of 12.5 to 25 mg every 4 weeks; maximum dose: 50 mg every 2 weeks (Ref). Dosage adjustments should not be made more frequently than every 4 weeks.
Conversion between oral and IM ER suspension: The manufacturer's labeling does not provide dose conversions to IM ER suspension based on current oral dose. Some experts recommend converting to IM ER suspension at the usual starting dose and titrating according to response (Ref). Some experts recommend the following conversions from oral to IM ER suspension (Ref):
≤3 mg/day oral = 25 mg IM ER suspension every 2 weeks.
>3 to ≤5 mg/day oral = 37.5 mg IM ER suspension every 2 weeks.
>5 mg/day oral = 50 mg IM ER suspension every 2 weeks.
Conversion between Risperdal Consta IM ER suspension and Rykindo IM ER suspension: Continue same dose, with first dose of Rykindo administered 4 to 5 weeks after last injection of Risperdal Consta. No oral overlap needed.
SUBQ ER suspension:
Note: Establish tolerability with oral risperidone before starting SUBQ ER suspension injection. Neither a loading dose nor overlap with oral risperidone is needed. Initiate the day after the last dose of oral therapy.
Monthly injection (Perseris):
Usual dose: SUBQ: 90 or 120 mg once monthly. Do not administer more than one 90 or 120 mg injection per month.
Monthly or every-2-months injection (Uzedy):
Usual dose: SUBQ: 50 to 125 mg once monthly or 100 to 250 mg every 2 months.
Conversion between oral and SUBQ ER suspension:
Monthly injection (Perseris):
Oral dose of 3 mg/day is equivalent to SUBQ ER suspension injection of 90 mg once monthly.
Oral dose of 4 mg/day is equivalent to SUBQ ER suspension injection of 120 mg once monthly.
Monthly or every-2-months injection (Uzedy):
Oral dose of 2 mg/day is equivalent to SUBQ ER suspension injection of 50 mg once monthly or 100 mg every 2 months.
Oral dose of 3 mg/day is equivalent to SUBQ ER suspension injection of 75 mg once monthly or 150 mg every 2 months.
Oral dose of 4 mg/day is equivalent to SUBQ ER suspension injection of 100 mg once monthly or 200 mg every 2 months.
Oral dose of 5 mg/day is equivalent to SUBQ ER suspension injection of 125 mg once monthly or 250 mg every 2 months.
Conversion between SUBQ ER suspension Uzedy once monthly and Uzedy every-2-months ER suspension injection: Administer the first dose of the new dosing regimen on the next scheduled date of administration in the original dosing regimen. Then proceed with new dosing schedule.
Tourette syndrome, management of tics (off-label use):
Oral: Initial: 0.25 to 0.5 mg/day; may increase gradually based on response and tolerability in increments of ≤1 mg/day every ≥2 days up to 6 mg/day; usual dose: 2.5 to 4 mg/day (Ref).
Discontinuation of therapy:
Oral: In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
Long-acting injection: Switching to other treatments is generally advised if side effects are intolerable or treatment is not effective. However, if a patient insists on stopping treatment, gradual dose reduction to avoid withdrawal reactions is generally not needed with long-acting injectable antipsychotics. The risk of withdrawal symptoms from discontinuation of long-acting injectables is low because the rate of drug elimination is slow. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
Switching antipsychotics: An optimal universal strategy for switching antipsychotic agents has not been established. Strategies include cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Ref). Based on clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Risperidone is extensively hepatically metabolized to 9-hydroxyrisperidone (9-OH-RIS [paliperidone]) (active metabolite) that is mainly excreted by the kidney (Ref). Risperidone and 9-hydroxyrisperidone clearance are decreased by ~60% in patients with CrCl <60 mL/minute/1.73 m2, which may increase risk of adverse effects (eg, orthostatic hypotension, QT prolongation) (Ref).
Altered kidney function:
Oral:
CrCl >60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 30 to 60 mL/minute: Initial: Administer 50% to 75% of the usual indication-specific dose; titrate cautiously based on tolerability and response in increments of no more than 0.5 mg twice daily and no more frequently than recommended for patients with normal kidney function; doses >1.5 mg twice daily should be titrated at intervals of ≥1 week. Maximum dose should not exceed 75% of the usual indication-specific dose (expert opinion derived from Gründer 2019; Snoeck 1995; manufacturer's labeling).
CrCl 10 to <30 mL/minute: Initial: Administer 50% of the usual indication-specific dose (Ref). Titrate cautiously in increments of no more than 0.5 mg twice daily and no more frequently than recommended for patients with normal kidney function; doses greater than >1.5 mg twice daily should be titrated at intervals of ≥1 week. Maximum dose should not exceed 50% of the usual indication-specific dose (expert opinion derived from Gründer 2019; Snoeck 1995; manufacturer's labeling).
CrCl <10 mL/minute: Consider alternative agent. If necessary, administer 25% of the usual indication-specific dose; titrate cautiously based on tolerability and response in increments of no more than 0.5 mg once daily and no more frequently than recommended for patients with normal kidney function (Ref).
IM ER suspension (Risperdal Consta and Rykindo): Must establish response and tolerability using oral risperidone before first injection; the manufacturer recommends patients should be able to achieve and tolerate an oral dose of at least 2 mg/day for at least 1 week before converting to IM ER suspension in patients with impaired kidney function. Due to delayed onset of the first IM ER suspension injection, an oral antipsychotic at an effective dose is overlapped for the first 3 weeks for Risperdal Consta and for the first week for Rykindo.
CrCl >60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 10 to ≤60 mL/minute:
Use with caution. Therapeutic drug monitoring and/or careful monitoring for dose-related side effects is recommended (Ref).
Initial: 12.5 to 25 mg every 2 weeks; dose may be increased based on response and tolerability in increments of 12.5 mg no more frequently than every 4 weeks (Ref).
CrCl <10 mL/minute:
Avoid use (preferred). If necessary, use with caution and closely monitor for adverse effects along with therapeutic drug monitoring.
Initial: 12.5 to 25 mg every 2 weeks; do not exceed 25 mg every 2 weeks (Ref).
SUBQ ER suspension:
Monthly injection (Perseris):
CrCl >60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 10 to ≤ 60 mL/minute: Use with caution (has not been studied); closely monitor for adverse effects along with therapeutic drug monitoring (if available) (Ref). Note: Use should only be considered in patients able to achieve and tolerate an oral dose of at least 3 mg/day; if tolerated and effective, transition to 90 mg SUBQ ER suspension injection (Perseris) monthly.
CrCl <10 mL/minute: Avoid use (Ref).
Monthly injection (Uzedy):
CrCl >60 mL/minute: No dosage adjustment necessary (Ref).
CrCl 10 to ≤60 mL/minute: Use with caution (has not been studied); closely monitor for adverse effects along with therapeutic drug monitoring (if available) (Ref). Note: Initiate with oral dosing (titrate up to ≥2 mg/day); if tolerated and effective, transition to 50 mg SUBQ ER suspension injection (Uzedy) monthly (Ref).
CrCl <10 mL/minute: Avoid use (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed (Ref):
Oral: Use with caution (has not been studied). Dose as for CrCl <10 mL/minute (Ref). Doses up to 2 mg/day have been tolerated in case reports (Ref).
IM ER suspension: Avoid use (preferred). If necessary, use with caution and closely monitor for adverse effects along with therapeutic drug monitoring. After establishing response and tolerability of at least 2 mg oral risperidone, 12.5 to 25 mg every 2 weeks may be initiated with 3 weeks of oral supplementation; do not exceed 25 mg every 2 weeks (Ref).
SUBQ ER suspension: Avoid use (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (high protein binding, moderate Vd) (Ref).
Oral: Use with caution (has not been studied). Dose as in CrCl <10 mL/minute (Ref).
IM ER suspension: Avoid use (preferred). If necessary, use with caution and closely monitor for adverse effects along with therapeutic drug monitoring. After establishing response and tolerability of at least 2 mg oral risperidone, 12.5 to 25 mg every 2 weeks may be initiated with 3 weeks of oral supplementation; do not exceed 25 mg every 2 weeks (Ref).
SUBQ ER suspension: Avoid use (Ref).
CRRT:
Oral: Use with caution (has not been studied). Dose as for CrCl 10 to 30 mL/minute (Ref).
IM, SUBQ ER suspension: Avoid use (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Oral: Use with caution (has not been studied). Dose as for CrCl 10 to 30 mL/minute (Ref).
IM, SUBQ ER suspension: Avoid use (Ref).
Oral: Note: Limiting initial doses to 1 mg daily (in 2 divided doses) may reduce the risk of orthostatic hypotension/syncope. The mean free fraction of risperidone in plasma may be increased by 35% in patients with hepatic impairment.
Mild or moderate impairment (Child-Pugh class A or B): There are no dosage adjustments provided in the manufacturer’s labeling; reduce dosage.
Severe impairment (Child-Pugh class C): Initial: 0.5 mg twice daily; titration should progress slowly in increments of no more than 0.5 mg twice daily; increases to dosages >1.5 mg twice daily should occur at intervals of ≥1 week.
IM ER suspension: Initiate with oral dosing (0.5 mg twice daily for 1 week then 1 mg twice daily or 2 mg once daily for 1 week); if tolerated, begin 25 mg IM ER suspension every 2 weeks; continue oral dosing for 3 weeks after the first IM injection. An initial IM dose of 12.5 mg may also be considered.
SUBQ ER suspension: Use with caution; has not been studied.
Monthly injection (Perseris): Initiate with oral dosing (titrate up to 3 mg/day); if tolerated and effective, transition to 90 mg SUBQ ER suspension injection (Perseris) once monthly.
Monthly injection (Uzedy): Initiate with oral dosing (titrate up to ≥2 mg/day); if tolerated and effective, transition to 50 mg SUBQ ER suspension injection (Uzedy) monthly .
Severe neutropenia (ANC <1,000/mm3): Discontinue treatment.
Note: Avoid for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. If used, consider deprescribing attempts to assess continued need and/or lowest effective dose. Of note, use in certain indications may be appropriate (eg, schizophrenia, bipolar disorder) (Ref).
Dosages in the lower range of recommended adult dosing are generally sufficient with late-onset-schizophrenia or psychosis (Ref).
Bipolar mania (monotherapy or as an adjunct to lithium or divalproex):
Oral: Initial: 0.5 mg twice daily; titrate slowly. Note: Limiting initial dose to 1 mg/day (in 2 divided doses) may reduce the risk of orthostatic hypotension/syncope. Additional monitoring of renal function and orthostatic blood pressure may be warranted.
IM ER suspension: Refer to adult dosing.
Schizophrenia:
Oral: Initial: 0.5 mg twice daily; titrate slowly. Note: Limiting initial dose to 1 mg/day (in 2 divided doses) may reduce the risk of orthostatic hypotension/syncope. Additional monitoring of renal function and orthostatic blood pressure may be warranted.
IM, SUBQ ER suspension: Refer to adult dosing.
(For additional information see "Risperidone: Pediatric drug information")
Bipolar mania: Children and Adolescents 10 to 17 years: Oral: Initial: 0.5 mg once daily; dose may be adjusted if needed, in increments of 0.5 to 1 mg/day at intervals ≥24 hours, as tolerated, to a dose of 2.5 mg/day. Doses ranging from 0.5 to 6 mg/day have been evaluated; however, doses >2.5 mg/day do not confer additional benefit and are associated with increased adverse events; doses >6 mg/day have not been studied. Note: May administer 1/2 the daily dose twice daily in patients who experience persistent somnolence. In patients ≥11 years, use of long-acting IM risperidone has been described (see "Parenteral therapy").
Delirium: Limited data available; optimal dose not established; experience suggests risperidone be considered for hypoactive or mixed delirium (Ref) dosing should be individualized to response and decreased as soon as appropriate (Ref):
Infants: Very limited data available: Oral: 0.05 to 0.1 mg once daily at bedtime or twice daily (Ref). Dosing based on experience with implementation of PICU assessment scales and treatment protocols, small open-label trials which included infants, and case series (Ref).
Children <5 years: Oral: Initial: 0.1 to 0.2 mg once daily at bedtime; doses may be increased based upon response; dosing based on experience with implementation of PICU assessment scales and treatment protocols, small open-label trials, and expert recommendations (Ref).
Children ≥5 years and Adolescents: Oral: Initial: 0.2 to 0.5 mg once daily at bedtime; may titrate to lowest effective dose every 1 to 2 days; usual range: 0.2 to 2.5 mg/day in divided doses 2 to 4 times daily; some have suggested maximum daily dose dependent upon patient weight: <20 kg: 1 mg/day; 20 to 45 kg: 2.5 mg/day; >45 kg: 3 mg/day (Ref).
Disruptive behavior disorders (eg, conduct disorder [CD], oppositional defiant disorder [ODD]): Limited data available:
Note: A systematic review suggested a high-quality of evidence that risperidone has a moderate effect on disruptive and aggressive behavior in pediatric patients with CD or ODD (with/without attention-deficit/hyperactivity disorder [ADHD]) with average IQ; in ODD or CD pediatric patients (with/without ADHD) with subaverage IQ, a moderate quality of evidence that risperidone has a moderate to large effect (Ref). In patients ≥11 years, use of long-acting IM risperidone has been described (see "Parenteral therapy").
Children ≥4 years and Adolescents: Oral: Initial: 0.01 mg/kg/dose once daily for 2 days, then 0.02 mg/kg/dose once daily; suggested initial fixed dose in patients <50 kg: 0.25 mg/day, and ≥50 kg: 0.5 mg/day. May further increase on weekly basis as tolerated to 0.06 mg/kg/dose once daily; usual maximum daily dose: 2 mg/day; improvement in target symptoms typically within 1 to 4 weeks (Ref). A large multicenter, double-blind, placebo-controlled trial including 335 patients (n=172 in treatment group; mean age: 10.9 ± 2.93 years) reported that a mean dose of 0.02 mg/kg/day resulted in significant positive changes in efficacy measurements/behavior scales and significantly longer time to symptom recurrence compared to placebo (Ref). Note: May divide dose and administer 1/2 the daily dose twice daily if breakthrough symptoms occur in the afternoon or evening or sedation.
Irritability including aggression, temper, tantrums, self-injurious behavior, and quickly changing moods associated with autism:
Children ≥5 years and Adolescents <18 years: Note: Individualize dose according to patient response and tolerability:
15 to 20 kg: Oral: Initial: 0.25 mg once daily; after ≥4 days, may increase dose to 0.5 mg/day; maintain this dose for ≥14 days. In patients not achieving sufficient clinical response, may increase dose in increments of 0.25 mg/day at ≥2-week intervals. Doses ranging from 0.5 to 3 mg/day have been evaluated; however, therapeutic effect reached plateau at 1 mg/day in clinical trials. Following clinical response, consider gradually decreasing dose to lowest effective dose. May be administered once daily or in divided doses twice daily.
≥20 kg: Oral: Initial: 0.5 mg once daily; after ≥4 days, may increase dose to 1 mg/day; maintain this dose for ≥14 days. In patients not achieving sufficient clinical response, may increase dose in increments of 0.5 mg/day at ≥2-week intervals. Doses ranging from 0.5 to 3 mg/day have been evaluated; however, therapeutic effect reached plateau at 2.5 mg/day (3 mg/day in pediatric patients >45 kg) in clinical trials. Following clinical response, consider gradually decreasing to lowest effective dose. May be administered once daily or in divided doses twice daily.
Schizophrenia: Adolescents 13 to 17 years: Oral: Initial: 0.5 mg once daily; dose may be adjusted if needed, in increments of 0.5 to 1 mg/day at intervals ≥24 hours, as tolerated, to a dose of 3 mg/day. Doses ranging from 1 to 6 mg/day have been evaluated; however, doses >3 mg/day do not confer additional benefit and are associated with increased adverse events. Note: May administer 1/2 the daily dose twice daily in patients who experience persistent somnolence. In patients ≥11 years, use of long-acting IM risperidone has been described (see "Parenteral therapy").
Tourette syndrome, tics: Limited data available; efficacy results variable (Ref): Compared to placebo, risperidone is probably more likely to reduce tic severity; reserve treatment for situations where benefits outweigh the risks; use lowest effective dose; monitor patients for movement, hormonal and metabolic adverse effects (Ref).
Children ≥7 years and Adolescents: Oral: Initial: 0.25 to 0.5 mg once daily at night; may gradually titrate every 4 to 5 days in 0.25 to 0.5 mg increments to usual reported therapeutic range: 0.25 to 6 mg/day divided in twice daily doses (Ref).
Parenteral therapy: Limited data available:
Note: Tolerability with oral risperidone should be established prior to transition to IM risperidone; based on pediatric trials and experience in adult patients, oral risperidone should be continued for 3 weeks after the first IM administration to ensure adequate therapeutic plasma concentrations are reached (Ref). Most commonly reported in situations to improve or ensure medication adherence.
Extended-released IM suspension (Risperdal Consta): Children ≥11 years and Adolescents: Maintenance therapy: Usual dose: IM: 25 to 37.5 mg every 2 weeks; dosing dependent on oral risperidone dosing regimen (some patients may require lower initial IM dose of 12.5 mg); titration at intervals of ≥4 weeks to higher doses (eg, 50 mg) may be necessary; most experience is in adolescent patients diagnosed bipolar disorder, schizophrenia, and CD (Ref).
Discontinuation of therapy: Children and Adolescents: American Academy of Child and Adolescent Psychiatry (AACAP), American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), National Institute for Health and Care Excellence (NICE), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (Ref); risk for withdrawal symptoms may be highest with highly anticholinergic or dopaminergic antipsychotics (Ref). When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months and the APA guidelines recommend reducing the dose by 10% each month (Ref). Continuing antiparkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Ref). When switching antipsychotics, three strategies have been suggested: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic), overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). Evidence supporting ideal switch strategies and taper rates is limited and results are conflicting (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity: Children ≥5 years and Adolescents: Severe neutropenia (ANC <1,000/mm3): Discontinue treatment.
There are no pediatric specific dosage recommendations; based on experience in adult patients, dosing adjustment suggested.
There are no pediatric specific dosage recommendations; based on experience in adult patients, dosing adjustment suggested.
Both activating effects (eg, akathisia, restlessness) and sedating effects (eg, sedated state, drowsiness) may occur with risperidone in all ages and lead to nonadherence or discontinuation. Sedation may result in subsequent falling, particularly in older adults. Individual patient experience can vary depending on the person's sensitivity toward activation or sedation and the dose used (Ref).
Mechanism: Dose-related (Ref); sedation is believed to be due to H1 antagonism leading to potential CNS depressant effects (Ref).
Risk factors:
• Young age (in general, children and adolescents appear to be at higher risk for sedation due to antipsychotics compared to adults (Ref); in studies that included risperidone in children and adolescents, younger age has been associated with activating symptoms and higher age has been associated with sedating symptoms) (Ref)
• Specific antipsychotic (risperidone is generally considered to be mildly sedating at usual therapeutic doses in comparison with other antipsychotics) (Ref)
Potentially life-threatening angioedema has been reported very rarely following oral and IM administration (Ref).
Mechanism: Unknown but both a nonallergic and allergic mechanism have been proposed, including IgE-related hypersensitivity, kinin-dependent processes, or C1-esterase inhibition deficiencies (Ref).
Onset: Varied; onset following oral therapy has been reported anywhere from <24 hours following a single initial dose to months after initiation (Ref); onset following parenteral administration usually occurs in the first 48 to 72 hours after injection (Ref).
Risk factors:
• Dose: Usually occurs after increasing the dose of risperidone (Ref), although has also been reported following a single dose (Ref)
• Concurrent use of ritonavir, a weak inhibitor of CYP2D6, may increase risperidone levels leading to cases of angioedema (Ref)
Antipsychotics are associated with dyslipidemia in adult and pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class. Although data are inconsistent regarding risperidone’s risk, the following events have been observed: Increased serum cholesterol, decreased HDL cholesterol, and/or increased serum triglycerides (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; metabolic alterations from antipsychotics can develop in as short as 3 months after initiation (Ref).
Risk factors:
• Children and adolescents may be at increased risk for increased serum triglycerides (Ref)
• Schizophrenia (regardless of medication use) is associated with a higher rate of morbidity/mortality compared to the general population primarily due to cardiovascular disease (Ref)
• Specific antipsychotic: Risperidone is usually considered to have a low to intermediate risk for causing lipid abnormalities in adults, although data are inconsistent (Ref)
Risperidone is frequently associated with extrapyramidal symptoms (EPS), also known as drug-induced movement disorders. Antipsychotics can cause 4 main EPS: Acute dystonia, drug-induced parkinsonism, akathisia, and tardive dyskinesia (Ref). EPS presenting as dysphagia, esophageal dysmotility, or aspiration have also been reported with antipsychotics, which may not be recognized as EPS (Ref).
Mechanism: EPS: Dose-related; due to antagonism of dopaminergic D2 receptors in nigrostriatal pathways (Ref). Tardive dyskinesia: Time-related (delayed); results from chronic exposure to dopamine 2 receptor antagonists leading to up-regulation of these receptors over time (Ref).
Onset:
Antipsychotics in general:
Acute dystonia: Rapid; in the majority of cases, dystonia usually occurs within the first 5 days after initiating antipsychotic therapy (and even with the first dose, particularly in patients receiving parenteral antipsychotics) or a dosage increase (Ref).
Drug-induced parkinsonism: Varied; onset may be delayed from days to weeks, with 50% to 75% of cases occurring within 1 month and 90% within 3 months of antipsychotic initiation, a dosage increase, or a change in the medication regimen (such as adding another antipsychotic agent or discontinuing an anticholinergic medication) (Ref).
Akathisia: Varied; may begin within several days after antipsychotic initiation but usually increases with treatment duration, occurring within 1 month in up to 50% of cases and within 3 months in 90% of cases (Ref).
Tardive dyskinesia: Delayed; symptoms usually appear after 1 to 2 years of continuous exposure to a dopamine 2 receptor antagonist and almost never before 3 months with an insidious onset, evolving into a full syndrome over days and weeks, followed by symptom stabilization and then a chronic waxing and waning of symptoms (Ref).
Esophageal dysfunction (associated with EPS): Varied; ranges from weeks to months following initiation (Ref).
Risk factors:
EPS (in general):
• Prior history of EPS (Ref)
• Higher doses (Ref)
• Younger age (in general, children and adolescents are usually at higher risk for EPS compared to adults) (Ref)
• Specific antipsychotic: Risperidone is usually associated with a moderate to high propensity to cause EPS (Ref).
Acute dystonia:
• Males (Ref)
• Young age (Ref)
Drug-induced parkinsonism:
• Females (Ref)
• Older patients (Ref)
Akathisia:
• Higher antipsychotic dosages (Ref)
• Polypharmacy (Ref)
• Mood disorders (Ref)
• Females (Ref)
• Older patients (Ref)
Tardive dyskinesia:
• Age >55 year (Ref)
• Cognitive impairment (Ref)
• Concomitant treatment with anticholinergic medications (Ref)
• Diabetes (Ref)
• Diagnosis of schizophrenia or affective disorders (Ref)
• Female sex (Ref)
• Greater total antipsychotic exposure (especially first-generation antipsychotics) (Ref)
• History of extrapyramidal symptoms (Ref)
• Substance misuse or dependence (Ref)
• Race (White or African descent). Note: Although early literature supported race as a potential risk factor for tardive dyskinesia (Morgenstern 1993), newer studies have challenged this assertion (Ref).
Esophageal dysfunction (associated with EPS):
• Certain comorbidities such as neurologic degenerative disease, dementia, stroke, Parkinson disease, or myasthenia gravis (Ref)
• Older adults >75 years of age (may be risk factor due to age-related muscle atrophy, cognitive impairment, reduced esophageal peristalsis) (Ref)
Leukopenia, neutropenia, and thrombocytopenia have been reported rarely with risperidone (Ref). Agranulocytosis has also been reported very rarely (Ref).
Mechanism: Unclear and poorly understood (Ref).
Onset: Varied; in general, drug-induced neutropenia usually manifests after 1 or 2 weeks of exposure and agranulocytosis usually appears 3 to 4 weeks following initiation of therapy; however, the onset may be insidious (Ref). In general, drug-induced thrombocytopenia usually occurs 5 to 15 days after initiation of therapy (Ref).
Risk factors:
• History of antipsychotic-induced neutropenia (Ref)
• Older adults (Ref)
• History of drug-induced leukopenia/neutropenia or low white blood cell count/absolute neutrophil count
Antipsychotics are associated with hyperglycemia in adult and pediatric patients, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class. Although data are inconsistent regarding risperidone’s risk, the following events have been observed: Increased serum glucose (fasting) and mild insulin resistance to some cases of new-onset diabetes mellitus and diabetic ketoacidosis (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; new-onset diabetes has been observed within the first 3 months to a median onset of 3.9 years (Ref).
Risk factors (in general):
• African American race (Ref)
• Males (Ref)
• Younger adults (Ref)
• Preexisting obesity, poor exercise habits, or other risk factors for diabetes, including family history of diabetes (Ref)
• Exposure to other agents that also increase the risk of hyperglycemia (Ref)
• Specific antipsychotic: Risk of hyperglycemia and/or new onset diabetes appears to be low to moderate with risperidone, although data are inconsistent (Ref).
Risperidone commonly causes hyperprolactinemia in adult and pediatric patients, which may lead to gynecomastia, galactorrhea not associated with childbirth, amenorrhea, sexual disorder, and infertility (Ref). Although long-term effects of elevated prolactin levels have not been fully evaluated, some studies have also suggested a possible association between hyperprolactinemia and an increased risk for breast and/or pituitary tumors and osteopenia/osteoporosis (Ref).
Mechanism: Dose-related and possibly time-related; antagonism of dopamine D2 receptors in the tuberoinfundibular dopaminergic pathway which causes disinhibition of prolactin release resulting in hyperprolactinemia (Ref); risperidone has been shown to cause a strong, more prolonged receptor blockade, resulting in a more pronounced and continuous increase in serum prolactin (Ref).
Onset: Varied; onset is typically within a few weeks following initiation or dosage increase, but may also arise after long-term stable use (Ref).
Risk factors:
• Specific antipsychotic: Risperidone is considered a prolactin-elevating antipsychotic with a high risk for hyperprolactinemia (Ref)
• Higher doses (Ref)
• Females (particularly those of reproductive age) (Ref)
• Children and adolescents (Ref)
Older adults with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature (Ref). In addition, an increased incidence of cerebrovascular effects (eg, cerebrovascular accident, transient ischemic attacks), including fatalities, have been reported in placebo-controlled risperidone trials in older adults with dementia-related psychosis (Ref). Of note, risperidone is not approved for the treatment of dementia-related psychosis.
Mechanism: Unknown; possible mechanisms include arrhythmia, cardiac arrest, and extrapyramidal effects that may increase the risk of falls, aspirations, and pneumonia (Ref).
Risk factors:
Antipsychotics in general:
• Higher antipsychotic dosage (Ref)
• Dementia-related psychosis (eg, Lewy body dementia, Parkinson disease dementia)
• Older adults
All antipsychotics have been associated with neuroleptic malignant syndrome (NMS), although the incidence is less with second-generation (atypical) antipsychotics compared to first-generation (typical) antipsychotics. There are case reports of NMS with risperidone monotherapy, although most involve concomitant administration of another psychotropic agent (Ref).
Mechanism: Non-dose-related; idiosyncratic. Believed to be due to a reduction in CNS dopaminergic tone, along with the dysregulation of autonomic nervous system activity (Ref).
Onset: Varied; in general, most patients develop NMS within 2 weeks of initiating an antipsychotic, and in some patients, prodromal symptoms emerge within hours of initiation; once the syndrome starts, the full syndrome usually develops in 3 to 5 days (Ref). However, there are many cases of NMS occurring months after stable antipsychotic therapy (Ref).
Risk factors:
Antipsychotics in general:
• Males (twice as likely to develop NMS compared to females) (Ref)
• Dehydration (Ref)
• High-dose antipsychotic treatment (Ref)
• Concomitant lithium or benzodiazepine (potential risk factors) (Ref)
• Catatonia (Ref)
• Polypharmacy (Ref)
• Pharmacokinetic interactions (Ref)
• IM administration (Ref)
• Rapid dosage escalation (Ref)
• Psychomotor agitation (Ref)
Additional risk factors for risperidone:
• Poor metabolizers of CYP2D6 (may be at increased risk) (Ref)
Orthostatic hypotension and accompanying dizziness, tachycardia, and syncope may occur, particularly with rapid titration and/or in older adults (which may result in subsequent falling and fracture) (Ref).
Mechanism: Orthostatic hypotension is attributed to alpha-1 receptor antagonism (Ref).
Onset: Rapid; per the manufacturer's labeling, orthostatic hypotension is most common during dose initiation, re-initiation, or increase.
Risk factors:
• Known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure, or conduction abnormalities) or cerebrovascular disease
• Known predisposing conditions (eg, hypovolemia/dehydration)
• Concomitant medications that also cause or exacerbate orthostatic hypotension (eg, tricyclic antidepressants, antihypertensive medications)
• Older adults
• Rapid dose titration (Ref)
Risperidone has been associated with prolonged QT interval on ECG , including reports of torsades de pointes (TdP), occurring predominately in patients with other TdP risk factors or receiving concomitant agents that can prolong the QTc interval and/or increase risperidone concentrations (Ref). Of the antipsychotics, risperidone is usually associated with a moderate risk for QTc-prolongation (particularly in older patients) (Ref). In a study in 28 healthy psychiatric patients reaching steady state on risperidone monotherapy (6 to 16 mg/day), the mean change in QTc was 3.6 to 3.9 ms (Ref).
Mechanism: Risperidone prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current, although other mechanisms might also be involved (Ref).
Risk factors:
Drug-induced QTc prolongation/TdP (in general):
• Females (Ref)
• Age >65 years (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure with a reduced ejection fraction) (Ref)
• History of drug-induced TdP (Ref)
• Genetic defects of cardiac ion channels (Ref)
• Congenital long QT syndrome (Ref)
• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)
• Electrolyte disturbances (eg, hypokalemia, hypocalcemia, hypomagnesemia) (Ref)
• Bradycardia (Ref)
• Hepatic impairment (Ref)
• Kidney impairment (Ref)
• Coadministration of multiple medications (≥2) that prolong the QT interval or increase drug interactions that increase serum drug concentrations of QTc prolonging medications (Ref)
• Substance use (Ref)
Additional risk factors for risperidone:
• Slow CYP2D6 metabolizers or patients taking other drugs that inhibit CYP2D6 (eg, fluoxetine, paroxetine) (Ref)
Antipsychotics have been associated with sexual disorders in both males and females. Antipsychotic treatment has been associated with effects on all phases of sexual activity (libido, arousal, and orgasm); however, many patients with schizophrenia experience more frequent sexual dysfunction, with or without antipsychotic treatment. The following adverse reactions have been observed with risperidone: Decreased libido, erectile dysfunction, and abnormal orgasm (Ref). In addition, priapism has been reported with risperidone (Ref).
Mechanism: Antipsychotic-induced sexual dysfunction has been attributed to many potential mechanisms, including dopamine receptor antagonism, dopamine D2 receptor antagonism in the infundibular dopaminergic pathway causing hyperprolactinemia, histamine receptor antagonism, cholinergic receptor antagonism, and alpha-adrenergic receptor antagonism (Ref). Of note, risperidone is associated with a high propensity for hyperprolactinemia (Ref). Priapism is believed to be caused by alpha-1 adrenergic antagonism; risperidone has a relatively high affinity for alpha-1 adrenergic receptors (Ref).
Risk factors:
• Hyperprolactinemia (although a correlation with sexual dysfunction has been observed, a relationship has not been confirmed) (Ref)
• Schizophrenia (the prevalence of antipsychotic-induced sexual dysfunction in patients with schizophrenia is high [~50% to 60% compared with 31% of men in the general population]) (Ref)
• Specific antipsychotic: Risperidone is associated with a high prevalence of sexual dysfunction (Ref).
Antipsychotics may impair the body’s ability to regulate core body temperature, which may cause a potentially life-threatening heat stroke during predisposing conditions, such as heat wave or strenuous exercise. There are also several case reports of potentially life-threatening hypothermia associated with risperidone use (Ref).
Mechanism: Non-dose-related; idiosyncratic. Exact mechanism is unknown; however, body temperature is regulated by the hypothalamus with involvement of the dopamine, serotonin, and norepinephrine neurotransmitters. D2 antagonism may cause an increase in body temperature, while 5-HT2A (serotonin) receptor antagonism may cause a decrease in body temperature. Of note, risperidone has pronounced 5-HT2A receptor antagonism, with stronger affinity for 5-HT2A receptors than for D2 receptors. In addition, antagonism of peripheral alpha-adrenergic receptors has also been suggested as a factor in the hypothermic effect by inhibiting peripheral responses to cooling (vasoconstriction and shivering) (Ref).
Onset: Hypothermia: Varied; antipsychotic-induced hypothermia cases indicate a typical onset in the period shortly after initiation of therapy or a dosage increase (first 7 to 10 days) (Ref).
Risk factors:
Heat stroke:
• Psychiatric illness (regardless of medication use) (Ref)
• Dehydration (Ref)
• Strenuous exercise (Ref)
• Heat exposure (Ref)
• Concomitant medications possessing anticholinergic effects (Ref)
Hypothermia:
• In general, predisposing risk factors include: Older adults, cerebrovascular accident, preexisting brain damage, hypothyroidism, malnutrition, shock, sepsis, adrenal insufficiency, diabetes, disability, burns, exfoliative dermatitis benzodiazepine use, alcohol intoxication, kidney or liver failure (Ref)
• Schizophrenia (regardless of antipsychotic use) (Ref)
Risperidone is associated with significant weight gain (increase of ≥7% from baseline) in all ages, which is a component of the metabolic syndrome observed with this pharmacologic class (Ref).
Mechanism: Multiple proposed mechanisms, including actions at serotonin, dopamine, histamine, and muscarinic receptors, with differing effects explained by differing affinity of antipsychotics at these receptors (Ref).
Onset: Varied; antipsychotic-induced weight gain usually occurs rapidly in the initial period following initiation, then gradually decreases and flattens over several months with patients continuing to gain weight in the long term (Ref).
Risk factors:
• Family history of obesity (Ref)
• Parental BMI (Ref)
• Children and adolescents (Ref)
• Rapid weight gain in the initial period: Younger age, lower baseline BMI, more robust response to antipsychotic, and increase in appetite; rapid weight gain of >5% in the first month has been observed as the best predictor for significant long-term weight gain (Ref)
• Duration of therapy (although weight gain plateaus, patients continue to gain weight over time) (Ref)
• Schizophrenia (regardless of medication) is associated with a higher prevalence of obesity compared to the general population due to components of the illness, such as negative symptoms, sedentary lifestyles, and unhealthy diets (Ref)
• Specific antipsychotic: Risperidone is considered to have an intermediate/moderate propensity for causing weight gain; olanzapine and clozapine are associated with a high risk (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Hyperprolactinemia (children and adolescents: 49% to 87%; adults: <4%), weight gain (≥7% kg increase from baseline: 8% to 42%) (table 1)
|
Drug (Risperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Risperidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|---|
|
33% |
7% |
Children and adolescents |
0.5 to 6 mg/day |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or other psychiatric disorders |
448 |
375 |
≥7% gain in body weight |
|
42% |
18% |
Adults |
120 mg every 4 weeks |
SUBQ extended-release injection |
Schizophrenia |
112 |
107 |
≥7% gain in body weight |
|
33% |
18% |
Adults |
90 mg every 4 weeks |
SUBQ extended-release injection |
Schizophrenia |
105 |
107 |
≥7% gain in body weight |
|
10% |
6% |
Adults |
25 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
90 |
83 |
≥7% gain in body weight |
|
8% |
6% |
Adults |
50 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
87 |
83 |
≥7% gain in body weight |
|
21% |
3% |
Adults |
>8 to 16 mg/day |
Oral |
Schizophrenia or bipolar mania |
158 |
597 |
≥7% gain in body weight |
|
9% |
3% |
Adults |
1 to 8 mg/day |
Oral |
Schizophrenia or bipolar mania |
769 |
597 |
≥7% gain in body weight |
Gastrointestinal: Constipation (5% to 17%), increased appetite (children and adolescents: 4% to 44%; adults: 2% to 4%), nausea (3% to 16%), upper abdominal pain (adolescents: 13% to 16%), vomiting (children and adolescents: 10% to 20%; adults: <4%)
Genitourinary: Urinary incontinence (children: 16%; adults <4%)
Nervous system: Akathisia (≤11%) (table 2), anxiety (6% to 16%), dizziness (3% to 16%) (table 3), drooling (children: 12%; adults: <4%), drowsiness, extrapyramidal reaction (2% to 35%), fatigue (children and adolescents: 18% to 31%; adults: 1% to 9%), headache (12% to 21%), insomnia (adults: 25% to 32%), parkinsonism (6% to 28%) (table 4), sedated state, tremor (children and adolescents: 8% to 11%; adults: 2% to 24%; including head titubation)
|
Drug (Risperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Risperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
8% |
2% |
Children and adolescents |
3 to 6 mg/day |
Oral |
Bipolar mania |
61 |
58 |
|
0% |
2% |
Children and adolescents |
0.5 to 2.5 mg/day |
Oral |
Bipolar mania |
50 |
58 |
|
10% |
4% |
Children and adolescents |
4 to 6 mg/day |
Oral |
Schizophrenia |
51 |
54 |
|
9% |
4% |
Children and adolescents |
1 to 3 mg/day |
Oral |
Schizophrenia |
55 |
54 |
|
9% |
3% |
Adults |
1 to 6 mg/day |
Oral |
Bipolar mania |
448 |
424 |
|
11% |
6% |
Adults |
50 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
103 |
98 |
|
10% |
3% |
Adults |
2 to 8 mg/day |
Oral |
Schizophrenia |
366 |
225 |
|
10% |
3% |
Adults |
>8 to 16 mg/day |
Oral |
Schizophrenia |
198 |
225 |
|
7% |
4% |
Adults |
120 mg every 4 weeks |
SUBQ extended-release injection |
Schizophrenia |
117 |
118 |
|
4% |
6% |
Adults |
25 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
99 |
98 |
|
3% |
4% |
Adults |
90 mg every 4 weeks |
SUBQ extended-release injection |
Schizophrenia |
115 |
118 |
|
Drug (Risperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Risperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
16% |
5% |
Children and adolescents |
0.5 to 2.5 mg/day |
Oral |
Bipolar mania |
50 |
58 |
|
13% |
5% |
Children and adolescents |
3 to 6 mg/day |
Oral |
Bipolar mania |
61 |
58 |
|
8% |
2% |
Children and adolescents |
0.5 to 4 mg/day |
Oral |
Irritability associated with autistic disorder |
107 |
115 |
|
14% |
2% |
Children and adolescents |
4 to 6 mg/day |
Oral |
Schizophrenia |
51 |
54 |
|
7% |
2% |
Children and adolescents |
1 to 3 mg/day |
Oral |
Schizophrenia |
55 |
54 |
|
3% |
1% |
Adults |
12.5 to 50 mg every 2 weeks |
IM extended-release injection |
Bipolar I disorder |
154 |
149 |
|
6% |
5% |
Adults |
1 to 6 mg/day |
Oral |
Bipolar mania |
448 |
424 |
|
11% |
6% |
Adults |
50 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
103 |
98 |
|
7% |
2% |
Adults |
2 to 8 mg/day |
Oral |
Schizophrenia |
366 |
225 |
|
7% |
6% |
Adults |
25 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
99 |
98 |
|
4% |
2% |
Adults |
>8 to 16 mg/day |
Oral |
Schizophrenia |
198 |
225 |
|
Drug (Risperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Risperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
12% |
3% |
Children and adolescents |
3 to 6 mg/day |
Oral |
Bipolar mania |
61 |
58 |
|
6% |
3% |
Children and adolescents |
0.5 to 2.5 mg/day |
Oral |
Bipolar mania |
50 |
58 |
|
8% |
1% |
Children and adolescents |
0.5 to 4 mg/day |
Oral |
Irritability associated with autistic disorder |
107 |
115 |
|
28% |
11% |
Children and adolescents |
4 to 6 mg/day |
Oral |
Schizophrenia |
51 |
54 |
|
16% |
11% |
Children and adolescents |
1 to 3 mg/day |
Oral |
Schizophrenia |
55 |
54 |
|
25% |
9% |
Adults |
1 to 6 mg/day |
Oral |
Bipolar mania |
448 |
424 |
|
17% |
8% |
Adults |
>8 to 16 mg/day |
Oral |
Schizophrenia |
198 |
225 |
|
15% |
9% |
Adults |
50 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
103 |
98 |
|
14% |
8% |
Adults |
2 to 8 mg/day |
Oral |
Schizophrenia |
366 |
225 |
|
8% |
9% |
Adults |
25 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
99 |
98 |
Respiratory: Cough (children: 17%; adults: 2% to 4%), nasopharyngitis (children: 19%; adults: 3% to 4%), rhinorrhea (children: 12%; adults: <4%)
Miscellaneous: Fever (children: 16%; adults: 1% to 2%)
1% to 10%:
Cardiovascular: Bradycardia, bundle branch block, chest discomfort, chest pain, ECG changes, first-degree atrioventricular block, hypertension (3%), hypotension, orthostatic dizziness, orthostatic hypotension, palpitations, peripheral edema (≤3%), prolonged QT interval on ECG, syncope (≤2%) (table 5), tachycardia
|
Drug (Risperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Risperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
2% |
0% |
Adults |
25 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
99 |
98 |
|
1% |
0% |
Adults |
50 mg every 2 weeks |
IM extended-release injection |
Schizophrenia |
103 |
98 |
|
0.8% |
N/A |
Adults |
N/A |
IM extended-release injection |
Schizophrenia |
1,499 |
N/A |
|
0.2% |
N/A |
Adults |
N/A |
Oral |
Schizophrenia |
2,607 |
N/A |
Dermatologic: Acne vulgaris (2%), eczema, pruritus, skin rash (1% to 8%), xeroderma (1% to 3%)
Endocrine & metabolic: Amenorrhea (4%), decreased HDL cholesterol, decreased libido, galactorrhea not associated with childbirth, gynecomastia, hyperglycemia, increased serum cholesterol (2% to 6%) (table 6), increased serum triglycerides (3% to 7%) (table 7), increased thirst (children: 7%), irregular menses, menstrual disease, menstruation (delayed), weight loss (1% to 4%)
|
Drug (Risperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Risperidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|---|
|
4% |
2% |
Children and adolescents |
0.5 to 6 mg/day |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or other psychiatric disorders |
80 |
42 |
<170 mg/dL to ≥200 mg/dL |
|
2% |
2% |
Adults |
90 mg every 4 weeks |
SUBQ extended-release injection |
Schizophrenia |
104 |
109 |
≥300 mg/dL |
|
2% |
2% |
Adults |
120 mg every 4 weeks |
SUBQ extended-release injection |
Schizophrenia |
111 |
109 |
≥300 mg/dL |
|
6% |
3% |
Adults |
>8 to 16 mg/day |
Oral |
Schizophrenia or bipolar mania |
96 |
368 |
<200 mg/dL to ≥240 mg/dL |
|
4% |
3% |
Adults |
1 to 8 mg/day |
Oral |
Schizophrenia or bipolar mania |
516 |
368 |
<200 mg/dL to ≥240 mg/dL |
|
Drug (Risperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Risperidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|---|
|
7% |
2% |
Children and adolescents |
0.5 to 6 mg/day |
Oral |
Schizophrenia, bipolar mania, autistic disorder, or other psychiatric disorders |
113 |
65 |
<150 mg/dL to ≥200 mg/dL |
|
3% |
1% |
Adults |
1 to 8 mg/day |
Oral |
Schizophrenia or bipolar mania |
301 |
180 |
<500 mg/dL to ≥500 mg/dL |
|
3% |
1% |
Adults |
>8 to 16 mg/day |
Oral |
Schizophrenia or bipolar mania |
121 |
180 |
<500 mg/dL to ≥500 mg/dL |
Gastrointestinal: Abdominal distress (1% to 3%), abdominal pain, anorexia, decreased appetite (6%), diarrhea (1% to 8%), dyspepsia (3% to 10%), gastritis, gastroenteritis, sialorrhea (1% to 10%), stomach discomfort (2% to 6%), toothache (≤3%), xerostomia (2% to 10%)
Genitourinary: Cystitis, delayed ejaculation, erectile dysfunction, glycosuria, infrequent uterine bleeding, mastalgia, sexual disorder, urinary tract infection
Hematologic & oncologic: Anemia, neutropenia
Hepatic: Increased gamma-glutamyl transferase, increased liver enzymes, increased serum alanine aminotransferase, increased serum aspartate aminotransferase
Hypersensitivity: Facial edema, hypersensitivity reaction
Infection: Infection, influenza, viral infection
Local: Abscess at injection site, induration at injection site, injection-site reaction, local pain (buttock), localized infection, pain at injection site, swelling at injection site
Nervous system: Abnormal gait (4%), agitation, akinesia, asthenia (1% to 2%), ataxia, depression, disturbance in attention (4%), dysarthria, falling, hypoesthesia (2%), lethargy, malaise, myasthenia, nervousness, pain (1% to 4%), paresthesia, procedural pain, seizure, sleep disturbance, vertigo
Neuromuscular & skeletal: Abnormal posture, arthralgia (2% to 4%), back pain (1% to 7%), dyskinesia (adults: 6%), dystonia (≤6%) (table 8), hypokinesia, increased creatine phosphokinase in blood specimen (1% to 2%), limb pain (≤8%), muscle rigidity (≤3%), muscle spasm (3%), musculoskeletal chest pain, musculoskeletal pain (5%), myalgia, neck pain, tardive dyskinesia
|
Drug (Risperidone) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Risperidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
6% |
0% |
Children and adolescents |
0.5 to 2.5 mg/day |
Oral |
Bipolar mania |
50 |
58 |
|
5% |
0% |
Children and adolescents |
3 to 6 mg/day |
Oral |
Bipolar mania |
61 |
58 |
|
6% |
0% |
Children and adolescents |
4 to 6 mg/day |
Oral |
Schizophrenia |
51 |
54 |
|
2% |
0% |
Children and adolescents |
1 to 3 mg/day |
Oral |
Schizophrenia |
55 |
54 |
|
5% |
1% |
Adults |
1 to 6 mg/day |
Oral |
Bipolar mania |
448 |
424 |
|
4% |
2% |
Adults |
>8 to 16 mg/day |
Oral |
Schizophrenia |
198 |
225 |
|
3% |
2% |
Adults |
2 to 8 mg/day |
Oral |
Schizophrenia |
366 |
225 |
|
0.9% |
3% |
Adults |
120 mg every 4 weeks |
SUBQ extended-release injection |
Schizophrenia |
117 |
118 |
|
0% |
3% |
Adults |
90 mg every 4 weeks |
SUBQ extended-release injection |
Schizophrenia |
115 |
118 |
Ophthalmic: Blurred vision (2% to 7%), conjunctivitis, decreased visual acuity
Otic: Otalgia, otic infection
Respiratory: Bronchitis, dyspnea, epistaxis (≤2%), flu-like symptoms, nasal congestion (4% to 10%), paranasal sinus congestion (2%), pharyngitis, pharyngolaryngeal pain (3% to 10%), pneumonia, respiratory tract infection (8%), rhinitis (9%), sinusitis
Frequency not defined:
Cardiovascular: Cold extremity, flushing
Dermatologic: Cheilitis, dermatitis (acarodermatitis), erythema of skin, hyperkeratosis, maculopapular rash, night sweats, onychomycosis, papular rash, seborrhea, seborrheic dermatitis of scalp, skin discoloration, skin lesion
Endocrine & metabolic: Diabetic coma, hypertriglyceridemia, pituitary neoplasm, polydipsia
Gastrointestinal: Bruxism, esophageal motility disorder, fecal incontinence, fecaloma, oral hypoesthesia, tongue paralysis, tongue spasm
Genitourinary: Anorgasmia, breast engorgement, breast hypertrophy, breast secretion, breast tenderness, dysuria, hypomenorrhea, pollakiuria, vaginal discharge
Hematologic & oncologic: Eosinophilia, granulocytopenia
Nervous system: Blunted affect, cerebral ischemia, cerebrovascular accident, cerebrovascular disease, chills, cogwheel rigidity, coma, confusion, impaired consciousness, loss of balance, mask-like face, movement disorder, restlessness, speech disturbance, transient ischemic attacks, trismus, unresponsive to stimuli, voice disorder
Neuromuscular & skeletal: Joint stiffness, joint swelling, muscle twitching, rhabdomyolysis, torticollis
Ophthalmic: Abnormal eye movements, crusting of eyelid, dry eye syndrome, eye discharge, eye infection, glaucoma, lacrimation, ocular hyperemia, photophobia, visual disturbance
Otic: Otitis media, tinnitus
Respiratory: Aspiration pneumonia, bronchopneumonia, hyperventilation, nasal mucosa swelling, rales, respiratory congestion, respiratory distress, tonsillitis, tracheobronchitis, wheezing
Postmarketing:
Cardiovascular: Atrial fibrillation, deep vein thrombosis (Konnakkaparambil Ramakrishnan 2021), edema (Liu 2020), pulmonary embolism, torsades de pointes (Beach 2018), ventricular tachycardia (Mazhar 2010)
Dermatologic: Alopecia, cellulitis, cutaneous nodule, dermal ulcer, Stevens-Johnson syndrome, toxic epidermal necrolysis
Endocrine & metabolic: Diabetes mellitus (new onset) (Farwell 2004), diabetic ketoacidosis (Ely 2013), heatstroke (Gomez Ramos 2012), hypoglycemia (Nagamine 2016), increased serum glucose (fasting) (Murashita 2007), insulin resistance (Sukasem 2018), precocious puberty, SIADH (Lee 2015), water intoxication
Gastrointestinal: Dysgeusia, dysphagia (Crouse 2018), intestinal obstruction, oromandibular dystonia (Yoshimura 2016), pancreatitis (Kawabe 2014)
Genitourinary: Abnormal orgasm (Nagaraj 2009), ejaculation failure (Cichon 2023), priapism (Ateb 2022), retrograde ejaculation (Cichon 2023), urinary retention (Ou 2021)
Hematologic & oncologic: Agranulocytosis (Finkel 1998), hematoma, leukopenia (Dernovsek 1997), thrombocytopenia (Semba 2009), thrombotic thrombocytopenic purpura
Hepatic: Jaundice
Hypersensitivity: Anaphylaxis, angioedema (Samra 2018)
Nervous system: Catatonia (Mall 2008, Parraga 2006), hyperthermia, hypothermia (Razaq 2004), mania (Terao 1998), neuroleptic malignant syndrome (Aboraya 2002), somnambulism, stuttering (Sood 2022)
Ophthalmic: Blepharospasm (Yoshimura 2016), cataract (Balamurugan 2020), intraoperative floppy iris syndrome (with cataract surgery) (Ford 2011)
Respiratory: Sleep apnea
Miscellaneous: Tissue necrosis
Hypersensitivity (eg, anaphylaxis, angioedema) to risperidone, paliperidone, or any component of the formulation.
Concerns related to adverse effects:
• Anticholinergic effects: May cause anticholinergic effects (confusion, agitation, constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, xerostomia, or visual problems. Relative to other neuroleptics, risperidone has a low potency of cholinergic blockade (Richelson 1999).
• Suicidal ideation: The possibility of a suicide attempt is inherent in psychotic illness or bipolar disorder; use with caution in high-risk patients during initiation of therapy. Prescriptions should be written for the smallest quantity consistent with good patient care.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with severe cardiac disease, hemodynamic instability, prior myocardial infarction or ischemic heart disease.
• Hepatic impairment: Use with caution in patients with hepatic disease or impairment; dosage reduction is recommended.
• Renal impairment: Use with caution in patients with renal disease; dosage reduction is recommended.
• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.
• Dispersible tablet: Inform patients with phenylketonuria that dispersible tablets contain phenylalanine.
• SUBQ injection site reactions: Following each SUBQ injection, a lump may develop and persist for several weeks; it will decrease in size over time. Do not rub or massage the injection site.
Other warnings/precautions:
• Discontinuation of therapy: When discontinuing antipsychotic therapy, gradually taper antipsychotics to avoid physical withdrawal symptoms and rebound symptoms (APA [Keepers 2020]; WFSBP [Hasan 2012]). Withdrawal symptoms may include agitation, alternating feelings of warmth and cold, anxiety, diaphoresis, dyskinesia, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, and vertigo (Lambert 2007; Moncrieff 2020). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Patients with chronic symptoms, repeated relapses, and clear diagnostic features of schizophrenia are at risk for poor outcomes if medications are discontinued (APA [Keepers 2020]).
Long-term usefulness of risperidone should be periodically re-evaluated in patients receiving the drug for extended periods of time. Similar to adult experience, the American Academy of Child and Adolescent Psychiatry (AACAP) guidelines recommend gradually tapering antipsychotics to avoid discontinuation syndrome (withdrawal) symptoms and minimize the risk of relapse (AACAP [McClellan 2007]).
Risvan (risperidone extended-release injectable suspension): FDA approved March 2024; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Risvan is a once monthly IM injection indicated for the treatment of schizophrenia in adults. Consult the prescribing information for additional information.
Rykindo (risperidone extended-release injectable suspension): FDA approved January 2023; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Rykindo is indicated for the treatment of schizophrenia in adults and as monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder in adults. Consult the prescribing information for additional information.
Uzedy: FDA approved April 2023; anticipated availability is unknown. Information pertaining to the product within the monograph is pending revision. Uzedy is an extended-release injectable suspension administered subcutaneously every 1 to 2 months for the treatment of schizophrenia in adults. Consult prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Prefilled Syringe, Subcutaneous:
Perseris: 90 mg (1 ea); 120 mg (1 ea)
Solution, Oral:
RisperDAL: 1 mg/mL (30 mL) [contains benzoic acid]
Generic: 1 mg/mL (30 mL)
Suspension Prefilled Syringe, Subcutaneous:
Uzedy: 50 mg/0.14 mL (0.14 mL); 75 mg/0.21 mL (0.21 mL); 100 mg/0.28 mL (0.28 mL); 125 mg/0.35 mL (0.35 mL); 150 mg/0.42 mL (0.42 mL); 200 mg/0.56 mL (0.56 mL); 250 mg/0.7 mL (0.7 mL) [latex free]
Suspension Reconstituted ER, Intramuscular:
RisperDAL Consta: 12.5 mg (1 ea); 25 mg (1 ea); 37.5 mg (1 ea); 50 mg (1 ea)
Generic: 12.5 mg (1 ea); 25 mg (1 ea); 37.5 mg (1 ea); 50 mg (1 ea)
Suspension Reconstituted ER, Intramuscular [preservative free]:
Rykindo: 25 mg (1 ea)
Rykindo: 25 mg (1 ea) [contains polysorbate 80]
Rykindo: 37.5 mg (1 ea)
Rykindo: 37.5 mg (1 ea) [contains polysorbate 80]
Rykindo: 50 mg (1 ea)
Rykindo: 50 mg (1 ea) [contains polysorbate 80]
Tablet, Oral:
RisperDAL: 0.5 mg, 1 mg [contains corn starch]
RisperDAL: 2 mg [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake]
RisperDAL: 3 mg [contains corn starch, quinoline yellow (d&c yellow #10)]
RisperDAL: 4 mg [contains corn starch, fd&c blue #2 (indigo carm) aluminum lake, quinoline yellow (d&c yellow #10)]
Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg
Tablet Disintegrating, Oral:
Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg
May be product dependent
Prefilled Syringe (Perseris Subcutaneous)
90 mg (per each): $2,608.93
120 mg (per each): $3,478.61
Solution (RisperDAL Oral)
1 mg/mL (per mL): $6.57
Solution (risperiDONE Oral)
1 mg/mL (per mL): $4.87 - $5.59
Suspension Prefilled Syringe (Uzedy Subcutaneous)
50MG/0.14ML (per 0.14 mL): $1,537.44
75MG/0.21ML (per 0.21 mL): $2,306.28
100MG/0.28ML (per 0.28 mL): $3,075.12
125 mg/0.35ml (per 0.35 mL): $3,843.84
150MG/0.42ML (per 0.42 mL): $4,612.56
200MG/0.56ML (per 0.56 mL): $6,150.12
250 mg/0.7 mL (per 0.7 mL): $7,687.68
Suspension Reconstituted ER (RisperDAL Consta Intramuscular)
12.5 mg (per each): $368.77
25 mg (per each): $737.47
37.5 mg (per each): $1,106.26
50 mg (per each): $1,475.05
Suspension Reconstituted ER (risperiDONE Microspheres ER Intramuscular)
12.5 mg (per each): $350.33
25 mg (per each): $700.60
37.5 mg (per each): $1,050.94
50 mg (per each): $1,401.30
Suspension Reconstituted ER (Rykindo Intramuscular)
25 mg (per each): $737.47
37.5 mg (per each): $1,106.26
50 mg (per each): $1,475.05
Tablet, orally-disintegrating (risperiDONE Oral)
0.25 mg (per each): $4.48
0.5 mg (per each): $4.92
1 mg (per each): $5.50 - $5.74
2 mg (per each): $8.95 - $9.34
3 mg (per each): $11.29 - $11.78
4 mg (per each): $15.16 - $15.82
Tablets (RisperDAL Oral)
0.5 mg (per each): $5.53
1 mg (per each): $5.88
2 mg (per each): $9.83
3 mg (per each): $11.54
4 mg (per each): $15.50
Tablets (risperiDONE Oral)
0.25 mg (per each): $3.90
0.5 mg (per each): $4.27 - $4.80
1 mg (per each): $4.55 - $6.00
2 mg (per each): $7.60 - $7.61
3 mg (per each): $8.93
4 mg (per each): $12.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Prefilled Syringe, Subcutaneous:
Perseris: 90 mg (1 ea); 120 mg (1 ea)
Solution, Oral:
RisperDAL: 1 mg/mL ([DSC]) [contains benzoic acid]
Generic: 1 mg/mL (30 mL, 60 mL, 100 mL, 120 mL)
Suspension Reconstituted ER, Intramuscular:
RisperDAL Consta: 12.5 mg (1 ea); 25 mg (1 ea); 37.5 mg (1 ea); 50 mg (1 ea)
Tablet, Oral:
Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg
Tablet Disintegrating, Oral:
Generic: 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg
Oral: May be administered without regard to meals.
Oral solution can be administered directly from the provided calibrated oral dose syringe or may be mixed with water, coffee, orange juice, or low-fat milk, but is not compatible with cola or tea.
Risperdal M-Tab should not be removed from blister pack until administered. Do not push tablet through foil (tablet may become damaged); peel back foil to expose tablet. Using dry hands, place immediately on tongue. Tablet will dissolve within seconds and may be swallowed with or without liquid. Do not split or chew.
IM ER suspension: Shake syringe vigorously just before injection. For IM use only; do not administer via any other route. Do not combine 2 different dosage strengths into 1 single administration. Avoid inadvertent injection into vasculature. Do not substitute any components of the dose-pack. Administer entire contents of the vial to ensure correct dose is provided.
Risperdal Consta: Administer IM into either the deltoid muscle or the upper outer quadrant of the gluteal area. Injection should alternate between the 2 arms or buttocks. Administer with needle provided (1-inch needle for deltoid administration or 2-inch needle for gluteal administration).
Rykindo: Administer IM into gluteal area. Alternate injections between the 2 buttocks. Administer with needle provided.
SUBQ ER suspension: Administer SUBQ ER suspension into the abdomen or back of the upper arm. Choose an injection site with adequate SUBQ tissue that is free of skin conditions (eg, bruising, excessive pigment [including tattoo], infection, tender, callused, hard, irritation, lesions, nodules, redness, scarring or stretch marks).
Monthly injection (Perseris): It is recommended that the patient is in the supine position. Rotate injection sites. When product reaches room temperature for ≥15 minutes, administer with 18G x 5/8" safety needle provided. There may be a lump at the injection site for several weeks; this will decrease in size over time. Do not rub injection site; be aware of the placement of any belts, waistbands, sleeves, cuffs, or other clothing parts. Refer to manufacturer’s labeling for product-specific detail.
Monthly or every-2-months injection (Uzedy): Do not substitute any components of the dose pack; when product reaches room temperature for ≥30 minutes, administer with 21G x 5/8” needle provided. Resistance will be experienced during administration; do not use excessive force in an attempt to deliver medication faster. Refer to manufacturer’s labeling for product-specific detail.
Oral: May be administered without regard to meals.
Oral solution: May administer directly from the manufacturer provided calibrated oral syringe or may mix with water, coffee, orange juice, or low-fat milk; do not mix with cola or tea.
Orally disintegrating tablets: Do not remove tablet from blister pack until ready to administer; do not push tablet through foil (tablet may become damaged); peel back foil to expose tablet; use dry hands to remove tablet and place immediately on tongue; tablet will dissolve within seconds and may be swallowed with or without liquid; do not split or chew tablet.
Parenteral: Extended-release suspension (Risperdal Consta): IM: Children ≥11 years and Adolescents: For IM injection by a health care provider; do not administer IV. Shake syringe vigorously just before injection. Administer IM into either the deltoid muscle (using a 1-inch needle) or the upper outer quadrant of the gluteal area (using a 2-inch needed). Avoid inadvertent injection into vasculature. Injection should alternate between sides of the body. Do not combine 2 different dosage strengths into 1 single administration or use a different syringe other than the one provided to administer a partial dose. Do not substitute any components of the dose-pack. Administer entire contents of the vial to ensure correct dose is provided. For single use only; discard vial and vial adapter after use.
Long-acting IM injection:
Bipolar disorder: As monotherapy or as adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder.
Schizophrenia: Treatment of schizophrenia.
Oral:
Bipolar mania: As monotherapy or as adjunctive therapy to lithium or valproate for the treatment of acute mania or acute episodes with mixed features associated with bipolar disorder in adults or as monotherapy for the treatment of acute mania or acute episodes with mixed features associated with bipolar disorder in children and adolescents 10 to 17 years of age.
Irritability associated with autistic disorder: Treatment of irritability associated with autistic disorder in children and adolescents 5 to 17 years of age, including symptoms of aggression toward others, deliberate self-injuriousness, temper tantrums, and quickly changing moods.
Schizophrenia: Treatment of schizophrenia in adults and adolescents 13 to 17 years of age.
Subcutaneous injection:
Schizophrenia: Treatment of schizophrenia in adults.
Agitation/Aggression (severe, acute) associated with psychiatric disorders (eg, schizophrenia, bipolar disorder), substance intoxication, or other organic causes; Agitation/Aggression and psychosis associated with dementia, severe or refractory; Bipolar disorder, hypomania; Delusional disorder; Delusional infestation (delusional parasitosis); Huntington disease–associated chorea; Major depressive disorder (unipolar), treatment resistant; Obsessive-compulsive disorder, treatment resistant; Tourette syndrome
RisperiDONE may be confused with reserpine, rOPINIRole
RisperDAL may be confused with lisinopril, reserpine, Restoril, rOPINIRole
Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of stroke and a greater rate of cognitive decline and mortality in patients with dementia. Evidence also suggests there may be an increased risk of mortality with use independent of dementia. Avoid antipsychotics for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. Use of antipsychotics may be appropriate for FDA approved indications including schizophrenia, bipolar disorder, Parkinson disease psychosis, adjunctive therapy in major depressive disorder, or for short-term use as an antiemetic (Beers Criteria [AGS 2023]).
Substrate of CYP2D6 (major), CYP3A4 (major), P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Adagrasib: May enhance the QTc-prolonging effect of RisperiDONE. Adagrasib may increase the serum concentration of RisperiDONE. Management: Consider alternatives to this combination. If combined, monitor for increased risperidone toxicities, including QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Agents With Seizure Threshold Lowering Potential: May enhance the adverse/toxic effect of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Armodafinil: May decrease serum concentrations of the active metabolite(s) of RisperiDONE. Armodafinil may decrease the serum concentration of RisperiDONE. Risk C: Monitor therapy
Artemether and Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Asenapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Azithromycin (Systemic): May enhance the QTc-prolonging effect of RisperiDONE. Azithromycin (Systemic) may increase the serum concentration of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Benperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cariprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Ceritinib: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Clarithromycin: RisperiDONE may enhance the QTc-prolonging effect of Clarithromycin. Clarithromycin may increase the serum concentration of RisperiDONE. Management: Monitor for increased risperidone toxicities, including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
ClomiPRAMINE: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of ClomiPRAMINE. QT-prolonging Antipsychotics (Moderate Risk) may enhance the serotonergic effect of ClomiPRAMINE. This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor therapy
Clothiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CloZAPine: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
CloZAPine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of RisperiDONE. Management: Careful monitoring for risperidone toxicities and possible dose adjustment are recommended when combined with strong CYP2D6 inhibitors. See full interaction monograph for details. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Moderate) may decrease the serum concentration of RisperiDONE. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of RisperiDONE. CYP3A4 Inducers (Strong) may decrease the serum concentration of RisperiDONE. Management: Careful monitoring for reduced risperidone efficacy and possible dose adjustment are recommended when combined with strong CYP3A4 inducers. See full interaction monograph for details. Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Dabrafenib: May enhance the QTc-prolonging effect of RisperiDONE. Dabrafenib may decrease the serum concentration of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Also monitor for reduced risperidone efficacy. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination
Donepezil: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of DroPERidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
DroPERidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Encorafenib: RisperiDONE may enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease the serum concentration of RisperiDONE. Management: Careful monitoring for reduced risperidone efficacy and possible dose adjustment are recommended when combined with encorafenib. Additionally, monitor for increased QTc interval prolongation and arrhythmias. See full interaction monograph for details. Risk D: Consider therapy modification
Erythromycin (Systemic): RisperiDONE may enhance the QTc-prolonging effect of Erythromycin (Systemic). Erythromycin (Systemic) may increase the serum concentration of RisperiDONE. Management: Monitor for increased risperidone toxicities, including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Fexinidazole: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Fexinidazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fluorouracil Products: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Flupentixol: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Flupentixol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Flupentixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Galantamine: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy
Haloperidol: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor therapy
Haloperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Huperzine A: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Iloperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Imipramine: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). QT-prolonging Antipsychotics (Moderate Risk) may enhance the serotonergic effect of Imipramine. This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor therapy
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor therapy
Lonafarnib: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Lonafarnib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification
Lumateperone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lurasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mavorixafor: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination
MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Molindone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
OLANZapine: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
OLANZapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation, ventricular arrhythmias, including torsades de pointes, when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paliperidone: RisperiDONE may enhance the adverse/toxic effect of Paliperidone. Management: Additive paliperidone exposure is expected with this combination. Consider using an alternative combination when possible. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Periciazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Perphenazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Piperaquine: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination
Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid combination
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Promazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Propafenone: May enhance the QTc-prolonging effect of RisperiDONE. Propafenone may increase the serum concentration of RisperiDONE. Management: Monitor for increased risperidone toxicities, including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Propofol: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Propofol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Psilocybin: RisperiDONE may diminish the therapeutic effect of Psilocybin. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): May enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antipsychotics (Moderate Risk) may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of RisperiDONE. QT-prolonging Antipsychotics (Moderate Risk) may increase the serum concentration of RisperiDONE. Specifically, thioridazine may increase concentrations of risperidone. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): RisperiDONE may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QUEtiapine: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QUEtiapine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QUEtiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy
QuiNIDine: May enhance the QTc-prolonging effect of RisperiDONE. QuiNIDine may increase the serum concentration of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for risperidone toxicities, including QTc interval prolongation and TdP. Risperidone dose adjustment may also be needed. See full monograph for details. Risk D: Consider therapy modification
Quinidine (Non-Therapeutic): May enhance the QTc-prolonging effect of QT-prolonging CYP2D6 Substrates. Quinidine (Non-Therapeutic) may increase the serum concentration of QT-prolonging CYP2D6 Substrates. Risk X: Avoid combination
Rivastigmine: May enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Saquinavir: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Saquinavir. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Risk X: Avoid combination
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thioridazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Thiothixene: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Triptorelin: Hyperprolactinemic Agents may diminish the therapeutic effect of Triptorelin. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valproate Products: May enhance the adverse/toxic effect of RisperiDONE. Generalized edema has developed. Risk C: Monitor therapy
Vemurafenib: RisperiDONE may enhance the QTc-prolonging effect of Vemurafenib. Vemurafenib may increase the serum concentration of RisperiDONE. Management: Monitor for increased risperidone toxicities, including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Voriconazole: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Oral solution is not compatible with beverages containing tannin or pectinate (cola or tea). Management: Administer oral solution with water, coffee, orange juice, or low-fat milk.
Risperidone may cause hyperprolactinemia, which may cause a reversible decrease in reproductive function in females.
If treatment with an atypical antipsychotic is needed in a woman planning a pregnancy, use of an agent other than risperidone is preferred (Larsen 2015). When using the IM injection, patients should notify health care provider if they intend to become pregnant during therapy or within 12 weeks of last injection.
Risperidone and its metabolite cross the placenta (Newport 2007). Agenesis of the corpus callosum has been noted in one case report of an infant exposed to risperidone in utero; relationship to risperidone exposure is not known. Antipsychotic use during the third trimester of pregnancy has a risk for extrapyramidal symptoms (EPS) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor. These effects may be self-limiting and allow recovery within hours or days with no specific treatment, or they may be severe requiring prolonged hospitalization.
When using the IM injection, patients should notify health care provider if they become pregnant during therapy or within 12 weeks of last injection.
The ACOG recommends that therapy during pregnancy be individualized; treatment with psychiatric medications during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. Safety data related to atypical antipsychotics during pregnancy is limited. As a result, routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to an agent that the fetus has not yet been exposed to; consider risk:benefit (ACOG 2008). If treatment is initiated during pregnancy, use of an agent other than risperidone is preferred (Larsen 2015).
Health care providers are encouraged to enroll women 18 to 45 years of age exposed to risperidone during pregnancy in the Atypical Antipsychotics Pregnancy Registry (1-866-961-2388 or http://womensmentalhealth.org/research/pregnancyregistry/).
Risperidone and its active metabolite, 9-hydroxyrisperidone, are present in breast milk.
The relative infant dose (RID) of risperidone is 1.5% and the RID of 9-hydroxyrisperidone is 5.5% when calculated using the highest breast milk concentration located and compared to a weight-adjusted maternal dose of 2 mg/day. Per the manufacturer, the RID for risperidone and the metabolite range between 2.3% and 4.7% of the weight-adjusted maternal dose.
In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Larsen 2015).
The RID of risperidone was calculated using a milk concentration of 3 ng/mL, providing an estimated daily infant dose via breast milk of 0.45 mcg/kg/day. The RID of 9-hydroxyrisperidone was calculated using a milk concentration of 11 ng/mL, providing an estimated daily infant dose via breast milk of 1.65 mcg/kg/day. These milk concentrations were obtained following maternal administration of oral risperidone 2 mg/day, with sampling occurring 3 hours after the maternal dose following 6 days of therapy; treatment started 1 week postpartum (Aichhorn 2005). Peak milk concentrations appear to be within 2 to 4 hours after an oral maternal dose (Aichhorn 2005; Hill 2000; Ilett 2004).
In general, infants exposed to second generation antipsychotics via breast milk should be monitored weekly for the first month of exposure for symptoms, such as appetite changes, insomnia, irritability, or lethargy (Uguz 2016). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Based on available information, use of agents other than risperidone in breastfeeding women is preferred (Larsen 2015; Pacchiarotti 2016; Uguz 2016).
Oral: May be taken without regard to meals. Dispersible tablets contain phenylalanine.
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Frequency of Antipsychotic Monitoring for Risperidonea,b | ||
|---|---|---|
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Monitoring parameter |
Frequency of monitoring |
Comments |
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a For all monitoring parameters, it is appropriate for check at baseline and when clinically relevant (based on symptoms or suspected adverse reactions) in addition to the timeline. | ||
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b ADA 2004; APA [Keepers 2020]; De Hert 2011; Gugger 2011; manufacturer's labeling. | ||
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c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic. | ||
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d Risk factors for tardive dyskinesia include age >55 years; females; White or African ethnicity; presence of a mood disorder, intellectual disability, or CNS injury; and past or current EPS. | ||
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Adherence |
Every visit |
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Blood chemistries (electrolytes, renal function, liver function, TSH) |
Annually |
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CBC |
As clinically indicated |
Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia |
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Extrapyramidal symptoms |
Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high risk.c |
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Fall risk |
Every visit |
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Fasting plasma glucose/HbA1c |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow diabetes guidelines. |
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Lipid panel |
4 months after initiation; annually |
Check more frequently than annually if abnormal. Follow lipid guidelines. |
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Mental status and alertness |
Every visit |
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Metabolic syndrome history |
Annually |
Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease |
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Prolactin |
Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported. |
Hyperprolactinemia symptoms: Changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function |
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Tardive dyskinesia |
Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high risk.d |
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Vital signs (BP, orthostatics, temperature, pulse, signs of infection) |
Every visit (at least weekly during first 3 to 4 weeks of treatment); 4 weeks after dose change. |
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Weight/Height/BMI |
8 and 12 weeks after initiation and dose change; quarterly |
Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome. Consider changing antipsychotic if BMI increases by ≥1 unit. Some experts recommend checking weight and height at every visit. |
Risperidone plus 9-hydroxy-risperidone:
Timing of serum samples: Draw trough just before next dose (Hiemke 2018).
Therapeutic reference range: 20 to 60 ng/mL (SI: 48.8 to 146.4 nmol/L) (Hiemke 2018). Note: Dosing should be based on therapeutic response as opposed to serum concentrations; however, therapeutic drug monitoring can be used to confirm adherence (APA [Keepers 2020]).
Laboratory alert level: 120 ng/mL (SI: 292.8 nmol/L) (Hiemke 2018).
Risperidone is a benzisoxazole atypical antipsychotic with high 5-HT2 and dopamine-D2 receptor antagonist activity. Alpha1, alpha2 adrenergic, and histaminergic receptors are also antagonized with high affinity. Risperidone has low to moderate affinity for 5-HT1C, 5-HT1D, and 5-HT1A receptors, weak affinity for D1 and no affinity for muscarinics or beta1 and beta2 receptors.
Note: Following oral administration, the pharmacokinetics of risperidone and 9-hydroxyrisperidone in children were found to be similar to values in adults (after adjusting for differences in body weight).
Onset of action:
Agitation: Orally disintegrating tablet: Median time to calm: 70 minutes (Normann 2006).
Bipolar disorder, acute mania: Oral: Initial effects may be observed within days of treatment with continued improvements over 1 to 2 weeks (Goikolea 2013; Tohen 2000; Welten 2016).
Major depressive disorder, unipolar: Oral: Initial effects may be observed within 1 week with continued improvements over 6 to 12 weeks (Wen 2014).
Schizophrenia: Oral: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010).
Absorption:
Oral: Rapid and well absorbed; food does not affect rate or extent.
IM: <1% absorbed initially; main release occurs at ~3 weeks and is maintained from 4 to 6 weeks; release ends by 7 weeks.
SUBQ:
Monthly injection (Perseris): Two absorption peaks; first release occurs immediately after injection and second release occurs around 10 to 14 days; therapeutic levels maintained for 4 weeks after injection.
Monthly or every-2-months injection (Uzedy): Two absorption peaks, one resulting in therapeutic concentrations within 6 to 24 hours, followed by a second peak around 8 to 14 days; therapeutic levels maintained for 28 or 56 days after injection, depending on dose (Perlstein 2022; manufacturer’s labeling).
Distribution: Vd: 1 to 2 L/kg
Protein binding, plasma: Risperidone 90%; 9-hydroxyrisperidone: 77%; Note: Risperidone free fraction may be increased by ~35% in patients with hepatic impairment due to decreased concentrations of albumin and alpha-1 acid glycoprotein.
Metabolism: Extensively hepatic via CYP2D6 to 9-hydroxyrisperidone (similar pharmacological activity as risperidone); N-dealkylation is a second minor pathway; Note: 9-hydroxyrisperidone is the predominant circulating form and is approximately equal to risperidone in receptor binding activity; clinical effects are from combined concentrations of risperidone and 9-hydroxyrisperidone; clinically important differences between CYP2D6 poor and extensive metabolizers are not expected (pharmacokinetics of the sum of risperidone and 9-hydroxyrisperidone were similar in poor and extensive metabolizers).
Bioavailability:
Oral: 70%; Tablet (relative to solution): 94%; orally-disintegrating tablets and oral solution are bioequivalent to tablets.
IM: Deltoid IM injection is bioequivalent to gluteal IM injection.
Half-life elimination:
Active moiety (risperidone and its active metabolite 9-hydroxyrisperidone):
Oral: 20 hours (mean); prolonged in elderly patients.
Extensive metabolizers: Risperidone: 3 hours; 9-hydroxyrisperidone: 21 hours.
Poor metabolizers: Risperidone: 20 hours; 9-hydroxyrisperidone: 30 hours.
IM: 3 to 6 days; related to microsphere erosion and subsequent absorption of risperidone.
Risperidone: SUBQ:
Monthly injection (Perseris): 9 to 11 days.
Monthly or every-2-months injection (Uzedy): 14 to 22 days.
Time to peak, plasma:
Oral: Risperidone: Within 1 hour; 9-hydroxyrisperidone: Extensive metabolizers: 3 hours; Poor metabolizers: 17 hours.
SUBQ:
Monthly injection (Perseris): Risperidone: First peak: 4 to 6 hours; Second peak: 10 to 14 days.
Monthly or every-2-months injection (Uzedy): Risperidone and 9-hydroxyrisperidone: First peak: Results in therapeutic concentrations within 6 to 24 hours; Second peak: 8 to 14 days.
IM: Bimonthly (every 2 weeks) injection (Rykindo): Risperidone: 14 days; 9-hydroxyrisperidone 17 days
Excretion: Urine (70%; primarily as active metabolite); feces (14%) (Mannens 1993).
Altered kidney function: CrCl 10 to 60 mL/minute: Clearance of parent drug and active metabolite decreased ~60%.
Hepatic function impairment: Mean free fraction of risperidone in plasma increased approximately 35%.
Older adult: Oral: Renal clearance of parent drug and active metabolite was decreased.
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