Medically reviewed on September 10, 2018

Pronunciation

(ris PER i done)

Index Terms

• Risperdal M-Tab

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Oral:

RisperDAL: 1 mg/mL (30 mL) [contains benzoic acid]

Generic: 1 mg/mL (30 mL)

Suspension Reconstituted, Intramuscular:

RisperDAL Consta: 12.5 mg (1 ea); 25 mg (1 ea); 37.5 mg (1 ea); 50 mg (1 ea)

Tablet, Oral:

RisperDAL: 0.25 mg, 0.5 mg, 1 mg [contains corn starch]

RisperDAL: 2 mg [contains corn starch, fd&c yellow #6 aluminum lake]

RisperDAL: 3 mg [contains corn starch, fd&c yellow #10 (quinoline yellow)]

RisperDAL: 4 mg [contains corn starch, fd&c blue #2 aluminum lake, fd&c yellow #10 (quinoline yellow)]

Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg

Tablet Disintegrating, Oral:

RisperDAL M-TAB: 0.5 mg [DSC], 1 mg [DSC], 2 mg [DSC], 3 mg [DSC], 4 mg [DSC] [contains aspartame, peppermint oil (mentha piperita oil)]

RisperiDONE M-TAB: 0.5 mg, 1 mg, 2 mg, 3 mg [DSC], 4 mg [DSC] [contains aspartame]

Generic: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg

Brand Names: U.S.

• RisperDAL
• RisperDAL Consta
• RisperDAL M-TAB [DSC]
• RisperiDONE M-TAB

Pharmacologic Category

• Antimanic Agent
• Second Generation (Atypical) Antipsychotic

Pharmacology

Risperidone is a benzisoxazole atypical antipsychotic with high 5-HT₂- 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-HT_1C, 5-HT_1D, and 5-HT_1A receptors, weak affinity for D₁ and no affinity for muscarinics or beta₁ and beta₂ receptors.

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: 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.

Distribution

V_d: 1 to 2 L/kg

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)

Excretion

Urine (70%); feces (14%)

Time to Peak

Oral: Risperidone: Within 1 hour; 9-hydroxyrisperidone: Extensive metabolizers: 3 hours; Poor metabolizers: 17 hours

SubQ: Risperidone: First peak: 4 to 6 hours; Second peak: 10 to 14 days

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: 9 to 11 days

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

Special Populations: Renal Function Impairment

Moderate to severe

Cl of parent drug and active metabolite decreased 60%.

Special Populations: Hepatic Function Impairment

Mean free fraction of risperidone in plasma increased approximately 35%.

Special Populations: Elderly

Oral

Renal clearance of parent drug and active metabolite was decreased.

Use: Labeled Indications

Injection:

Bipolar disorder (IM injection only): 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:

Monotherapy: For the treatment of acute manic or mixed episodes associated with bipolar I disorder in adults and in children and adolescents 10 to 17 years of age

Adjunctive therapy: As adjunctive therapy with lithium or valproate for the treatment of adults with acute manic or mixed episodes associated with bipolar I disorder

Irritability associated with autistic disorder: For the 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: For the treatment of schizophrenia in adults and adolescents 13 to 17 years of age

Off Label Uses

Delusional infestation (also called delusional parasitosis)

Data from a limited number of patients studied in case reports suggest that risperidone may be beneficial for the treatment of delusional infestation (also called delusional parasitosis). Additional data may be necessary to further define the role of risperidone in this condition.

Major depressive disorder

Data from 2 meta-analyses of 4 randomized, double-blind, placebo controlled trials support the use of adjunctive risperidone (in combination with antidepressants) in the treatment of treatment resistant major depressive disorder ^{[Komossa 2010]}, ^{[Nelson 2009]}. Additional trials may be necessary to further define the role of risperidone in this condition.

Posttraumatic stress disorder

Data from several small, randomized, double-blind, placebo-controlled trials support the use of risperidone mono- or adjunctive therapy (primarily with antidepressants) in the treatment of posttraumatic stress disorder ^{[Bartzokis 2005]}, ^{[Hamner 2003]}, ^{[Padala 2006]}, ^{[Reich 2004]}, ^{[Rothbaum 2008]}. Additional trials may be necessary to further define the role of risperidone in this condition.

Based on the American Psychiatric Association (APA) practice guidelines for the Treatment of Patients with Post-Traumatic Stress Disorder and the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the Pharmacological Treatment of Post-Traumatic Stress Disorders, adjunctive risperidone is suggested as a treatment option for patients when concomitant psychotic symptoms are present or when first-line approaches have been ineffective in controlling symptoms.

Psychosis/agitation associated with dementia

Data from randomized, double-blind, placebo-controlled trials supports the use of risperidone in the treatment of psychosis/agitation related to dementia ^{[Brodaty 2003]}, ^{[De Deyn 1999]}, ^{[Katz 1999]}, ^{[Schneider 2006]}, ^{[Sultzer 2008]}. Additional trials may be necessary to further define the role of risperidone in this condition.

Based on the American Psychiatric Association (APA) practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia, antipsychotics, such as risperidone, may be considered for the treatment of agitation and psychosis in certain patients; however, evidence for efficacy is modest and use should be limited to patients whose symptoms are dangerous, severe, or cause significant patient distress due to safety risks associated with antipsychotic use. Based on the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the Biological Treatment of Alzheimer Disease and Other Dementias, drug treatment with risperidone for behavioral and psychological aspects (including hyperactivity and psychosis) is recommended at low doses and for short durations, as a last option after addressing causative factors and using psychosocial interventions.

Tourette syndrome

Data from small, double-blind, randomized, controlled trials support the use of risperidone in the treatment of Tourette syndrome in children, adolescents, and adults ^{[Bruggeman 2001]}, ^{[Dion 2002]}, ^{[Gaffney 2002]}, ^{[Ghanizadeh 2014]}, ^{[Gilbert 2004]}, ^{[Scahill 2003]}. Additional trials may be necessary to further define the role of risperidone in this condition.

Based on the European Society for the Study of Tourette Syndrome and the Tourette Canada Guidelines, drug therapy, including risperidone, is effective and recommended for the management of Tourette syndrome to improve quality of life with tics that are painful or distressing, interfere with daily functioning, or cause sustained social or emotional problems. Similarly, based on the American Academy of Child and Adolescent Psychiatry practice parameter for the treatment of Children and Adolescents with Tic Disorders, drug therapy, including risperidone, is effective and recommended for the management of moderate to severe tics causing severe impairment in quality of life in chronic tic disorders, including Tourette syndrome. Of the atypical antipsychotics, risperidone has the best evidence of efficacy for Tourette syndrome; however, Canadian guidelines consider risperidone a second-line option (after clonidine and guanfacine) due to its adverse effect profile and recommend avoiding use in patients who are overweight at baseline.

Contraindications

Hypersensitivity to risperidone, paliperidone, or any component of the formulation

Dosing: Adult

Note: When reinitiating treatment after discontinuation, the initial titration schedule should be followed. Limiting initial oral dose to 2 mg daily (in 1 or 2 divided doses) may reduce the risk of orthostatic hypotension/syncope.

Bipolar mania (monotherapy or as an adjunct to lithium or divalproex): Oral: Initial: 2 to 3 mg once daily; if needed, adjust dose by 1 mg daily in intervals ≥24 hours; dosing range: 1 to 6 mg daily

Maintenance: No dosing recommendation available for treatment >3 weeks' duration

Bipolar I maintenance (monotherapy or as an adjunct to lithium or divalproex): IM: 25 mg every 2 weeks; if unresponsive, some may benefit from larger doses (37.5 to 50 mg); maximum dose: 50 mg every 2 weeks. Dosage adjustments should not be made more frequently than every 4 weeks. A lower initial dose of 12.5 mg may be appropriate in some patients (eg, hepatic or renal impairment, poor tolerability to other psychotropic medications).

Note: Establishment of tolerability to oral risperidone is recommended prior to initiation of the intramuscular injection. Oral risperidone (or other antipsychotic) should be administered with the initial injection of the intramuscular injection and continued for 3 weeks (then discontinued) to maintain adequate therapeutic plasma concentrations prior to main release phase of risperidone from injection site.

Delusional infestation (also called delusional parasitosis) (off-label use): Oral: Initial: 0.5 mg at bedtime; increase gradually based on response and tolerability up to 1 to 2 mg given at bedtime or in 2 divided doses. Doses up to 8 mg/day have been evaluated (Freudenmann 2008; Heller 2013; Kenchaiah 2010). Additional data may be necessary to further define the role of risperidone in this condition.

Major depressive disorder (adjunct to antidepressants; off-label use): Oral: Initial: 0.25 mg to 0.5 mg daily; slowly adjust dose based on response and tolerability up to 3 mg/day (Keitner 2009; Mahmoud 2007; Rapaport 2006; Reeves 2008). Average doses in clinical trials were 1.2 to 1.6 mg/day (Komossa 2010)

Posttraumatic stress disorder (PTSD) (off-label use): Oral: Initial: 0.5 to 1 mg at bedtime or 0.5 mg twice daily; may adjust dose based on response and tolerability to a maximum of 8 mg daily; total daily dose may be given in 2 or 3 divided doses. Average dose in clinical trials: 1.25 to 3.75 mg daily (Bandelow 2008; Bartzokis 2005; Hamner 2003; Padala 2006; Reich 2004; Rothbaum 2008).

Schizophrenia:

Oral: Initial: 2 mg daily in 1 to 2 divided doses; may be increased by 1 to 2 mg daily at intervals ≥24 hours to a recommended dosage range of 4 to 8 mg daily. Daily dosages >6 mg do not appear to confer any additional benefit, and the incidence of extrapyramidal symptoms is higher than with lower doses. Dose range studied in clinical trials: 4 to 16 mg daily. Maintenance: Recommended dosage range: 2 to 8 mg daily

IM: Initial: 25 mg every 2 weeks; if unresponsive, some may benefit from larger doses (37.5 to 50 mg); maximum dose: 50 mg every 2 weeks. No additional benefit was observed with doses >50 mg; however, a higher incidence of adverse reactions was observed. Dosage adjustments should not be made more frequently than every 4 weeks. A lower initial dose of 12.5 mg may be appropriate in some patients (eg, demonstrated poor tolerability to other psychotropic medications).

Note: Establishment of tolerability to oral risperidone is recommended prior to initiation of the intramuscular injection. Oral risperidone (or other antipsychotic) should be administered with the initial injection of the intramuscular injection and continued for 3 weeks (then discontinued) to maintain adequate therapeutic plasma concentrations prior to main release phase of risperidone from injection site.

SubQ: Usual dose: 90 or 120 mg once monthly. Do not administer more than one 90 or 120 mg injection per month. Note: Establishment of tolerability to oral risperidone is recommended prior to initiation of the SubQ injection. Neither a loading dose nor oral overlap with risperidone is needed.

Conversion between oral risperidone to SubQ risperidone:

Oral dose of 3 mg/day is equivalent to SubQ injection of 90 mg once monthly.

Oral dose of 4 mg/day is equivalent to SubQ injection of 120 once monthly.

Tourette syndrome (off-label use): Oral: Initial: 0.25 mg once daily; increase gradually based on response and tolerability up to a usual dosage of 0.25 to 6 mg daily (Pringsheim 2012; Roessner 2011). Dosage adjustments in clinical trials were commonly in increments of <0.5 mg twice daily and at intervals ≥3 days (Bruggeman 2001; Dion 2002; Scahill 2003).

Concomitant CYP2D6 inhibitors: Addition of fluoxetine or paroxetine: SubQ:

In patients receiving 90 mg once monthly: Continue treatment with 90 mg unless clinical judgement necessitates interruption of SubQ treatment.

In patients receiving 120 mg once monthly: Reduce dose to 90 mg once monthly 2 to 4 weeks before the planned start of fluoxetine or paroxetine.

Concomitant CYP3A4 inducers:

Addition of carbamazepine or other known hepatic enzyme inducer: SubQ: Note: Monitor closely for the first 4 to 8 weeks:

In patients receiving 90 mg once monthly: Consider increasing risperidone to 120 mg once monthly.

In patients receiving 120 mg once monthly: Consider oral risperidone supplementation.

Discontinuation of carbamazepine or other known hepatic enzyme inducer: SubQ: Consider decreasing dose of risperidone SubQ injection from 120 mg to 90 mg and/or decreasing oral supplementation dose. In patients taking 90 mg risperidone injection once monthly, continue dose unchanged and monitor for worsening tolerability.

Discontinuation of therapy:American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (APA [Lehman 2004]; Cerovecki 2013; CPA [Addington 2005]; WFSBP [Hasan 2012]); risk for withdrawal symptoms may be highest with highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). 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 (APA [Lehman 2004]; CPA [Addington 2005]). Continuing anti-parkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Cerovecki 2013). When switching antipsychotics, 3 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 (Cerovecki 2013; Remington 2005).

Dosing: Geriatric

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 daily (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: Refer to adult dosing.

Psychosis/agitation associated with dementia (off-label use): Oral: Initial: 0.5 mg daily, in 1 to 2 divided doses; if necessary, gradually increase based on response and tolerability not to exceed 2 mg daily. Doses >1 mg daily are associated with higher rates of extrapyramidal symptoms. In patients without a clinically significant response after 4 weeks, taper and withdraw therapy. In patients with an adequate response, attempt to taper and withdraw therapy within 4 months, unless symptoms recurred with a previous taper attempt. Assess symptoms at least monthly during taper and for at least 4 months after withdrawal of therapy (APA [Reus 2016]; Brodaty 2003; De Deyn 1999; Katz 1999; Schneider 2006; Sultzer 2008).

Schizophrenia:

Oral: Initial: 0.5 mg twice daily; titrate slowly. Note: Limiting initial dose to 1 mg daily (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: Refer to adult dosing.

Dosing: Pediatric

Note: When reinitiating treatment after discontinuation, the initial titration schedule should be followed.

Bipolar mania (monotherapy or as an adjunct to lithium or divalproex): Children and Adolescents 10 to 17 years of age: Oral: Initial: 0.5 mg once daily; dose may be adjusted in increments of 0.5 to 1 mg daily at intervals ≥24 hours to a dose of 1 to 2.5 mg daily. Doses ranging from 0.5 to 6 mg daily have been evaluated; however doses >2.5 mg daily do not confer additional benefit and are associated with increased adverse events. Patients experiencing persistent somnolence may benefit from dividing the dosage into twice-daily doses.

Maintenance: No dosing recommendation available for treatment >3 weeks' duration

Irritability associated with autistic disorder: Children ≥5 years of age and Adolescents: Oral:

<15 kg: Use with caution; specific dosing recommendations not available

15 to <20 kg: Initial: 0.25 mg daily; may increase dose to 0.5 mg daily after ≥4 days, maintain dose for ≥14 days. In patients not achieving sufficient clinical response, may increase dose by 0.25 mg daily in ≥2-week intervals. Doses ranging from 0.5 to 3 mg daily have been evaluated. Following clinical response, consider gradually lowering dose. Patients experiencing persistent somnolence may benefit from a once-daily dose administered at bedtime, dividing the dosage into twice-daily doses, or a reduction of the dose.

≥20 kg: Initial: 0.5 mg daily; may increase dose to 1 mg daily after ≥4 days, maintain dose for ≥14 days. In patients not achieving sufficient clinical response, may increase dose by 0.5 mg daily in ≥2-week intervals. Doses ranging from 0.5 to 3 mg daily have been evaluated. Following clinical response, consider gradually lowering dose. Patients experiencing persistent somnolence may benefit from a once-daily dose administered at bedtime, dividing the dosage into twice-daily doses, or a reduction of the dose.

Schizophrenia: Adolescents 13 to 17 years of age: Oral: Initial: 0.5 mg once daily; dose may be adjusted in increments of 0.5 to 1 mg daily at intervals ≥24 hours to a dose of 3 mg daily. Doses ranging from 1 to 6 mg daily have been evaluated; however, doses >3 mg daily do not confer additional benefit and are associated with increased adverse events. Patients experiencing persistent somnolence may benefit from dividing the dosage into twice-daily doses.

Tourette syndrome (off-label use): Children and Adolescents: Oral: Initial: 0.125 to 0.5 mg once daily; increase gradually based on response and tolerability up to a usual dosage of 0.75 to 3 mg daily (AACAP [Murphy 2013]; Pringsheim 2012). Dosage adjustments in clinical trials were commonly in increments of <0.5 mg twice daily and at intervals ≥3 days; doses up to 4 mg daily have been evaluated in children and up to 6 mg daily in adolescents (Bruggeman 2001; Dion 2002; Ghanizadeh 2014; Gilbert 2004; Scahill 2003).

Dosing: Renal Impairment

Adults:

Oral: Note: Limiting initial dose to 1 mg daily (in 2 divided doses) may reduce the risk of orthostatic hypotension/syncope. Clearance may be decreased by 60% in patients with moderate to severe renal disease (CrCl <60 mL/minute).

Mild or moderate impairment (CrCl ≥30 mL/minute): There are no dosage adjustments provided in the manufacturer’s labeling; reduce dosage.

Severe impairment (CrCl <30 mL/minute): Initial: 0.5 mg twice daily; titrate 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: 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 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.

Dosing: Hepatic Impairment

Adults:

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: 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 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.

Reconstitution

IM: Do not substitute any components of the dose pack. Bring to room temperature for ≥30 minutes prior to reconstitution (do not warm any other way). Reconstitute with provided diluent only. Refer to the manufacturer's labeling for device assembly and reconstitution instructions. Do not store suspension after reconstitution; administer immediately after reconstitution.

SubQ: Reconstitute immediately prior to administration. Bring kit to room temperature ≥15 minutes prior to preparation. Refer to the manufacturer's labeling for reconstitution instructions. Administer immediately after mixing.

Administration

Oral: May be administered without regard to meals.

Oral solution can be administered directly from the provided calibrated pipette 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: Shake syringe vigorously just before injection. Administer IM into either the deltoid muscle or the upper outer quadrant of the gluteal area. For IM use only; do not administer IV. Avoid inadvertent injection into vasculature. Injection should alternate between the two arms or buttocks. Do not combine two different dosage strengths into one single administration. Do not substitute any components of the dose-pack; administer with needle provided (1-inch needle for deltoid administration or 2-inch needle for gluteal administration). Administer entire contents of the vial to ensure correct dose is provided.

SubQ: Administer SubQ into the abdomen only. Choose an injection site with adequate subcutaneous tissue that is free of skin conditions (eg, bruising, excessive pigment, infection, irritation, lesions, nodules, redness, or scarring). It is recommended that the patient is in the supine position. Rotate injection sites. 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 or clothing waistbands.

Dietary Considerations

May be taken without regard to meals. Dispersible tablets contain phenylalanine.

Storage

Injection:

IM: Store at 2°C to 8°C (36°F to 46°F) and protect from light. May be stored at 25°C (77°F) for up to 7 days prior to administration; do not expose unrefrigerated product to temperatures above 77°F (25°C). Following reconstitution, administer immediately (do not store for future use).

SubQ: Store at 2°C to 8°C (36°F to 46°F). Unopened package may be stored at 20°C to 25°C (68°F to 77°F) for up to 7 days prior to administration. Allow kit to come to room temperature for at least 15 minutes prior to mixing.

Oral solution, tablet: Store at 15°C to 25°C (59°F to 77°F). Protect from light and moisture. Keep orally-disintegrating tablets sealed in foil pouch until ready to use. Do not freeze solution.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Amifampridine: May diminish the anticholinergic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Amifampridine. Monitor therapy

Amisulpride: Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. 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 using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. Consider therapy modification

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. 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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. 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. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Cobicistat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Consider therapy modification

CYP3A4 Inducers (Strong): May decrease the serum concentration of RisperiDONE. Management: Consider increasing the dose of oral risperidone (to no more than double the original dose) if a strong CYP3A4 inducer is initiated. For patients on IM risperidone, consider an increased IM dose or supplemental doses of oral risperidone. Consider therapy modification

Darunavir: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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. Consider therapy modification

Hydroxychloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Imatinib: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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 anticonvulsants. 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 anticonvulsants. 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 anticonvulsants. Consider therapy modification

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of RisperiDONE. Monitor therapy

Macimorelin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. 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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Opioid Analgesics: CNS Depressants may enhance the CNS depressant effect of Opioid Analgesics. Management: Avoid concomitant use of opioid analgesics 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. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

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. 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. Consider therapy modification

Panobinostat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. 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). Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Perhexiline: CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

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. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Probucol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Promazine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

QTc-Prolonging Agents (Highest Risk): QTc-Prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Avoid combination

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

QTc-Prolonging Agents (Moderate Risk): May enhance the QTc-prolonging effect of other QTc-Prolonging Agents (Moderate Risk). Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of RisperiDONE. Exceptions: FluvoxaMINE. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. 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. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Valproate Products: May enhance the adverse/toxic effect of RisperiDONE. Generalized edema has developed. Monitor therapy

Verapamil: May increase the serum concentration of RisperiDONE. Monitor therapy

Vinflunine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Xipamide: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). 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. Consider therapy modification

Adverse Reactions

>10%:

Central nervous system: Sedation (children 12% to 63%; adults 5% to 11%), parkinsonian-like syndrome (children 6% to 62%; adults 8% to 25%), drowsiness (adults 5% to 41%; children 4% to 11%), insomnia (≤32%), fatigue (children 18% to 31%; adults 1% to 9%), headache (12% to 21%), anxiety (≤16%), dizziness (3% to 16%), drooling (children 12%; adults <4%), akathisia (5% to 11%)

Endocrine & metabolic: Weight gain (≥7% kg increase from baseline: children 8% to 33%; adults 4% to 21%)

Gastrointestinal: Increased appetite (children 4% to 44%; adults 4%), vomiting (children 10% to 20%; adults <4%), constipation (5% to 17%), abdominal pain (children 6% to 16%; adults <4%), nausea (5% to 16%)

Genitourinary: Urinary incontinence (children 16%; adults <4%)

Neuromuscular & skeletal: Tremor (adults ≤24%; children ≤11%)

Respiratory: Nasopharyngitis (children 19%; adults ≤4%), cough (children ≤17%; adults ≤4%), rhinorrhea (children 12%; adults <4%)

Miscellaneous: Fever (children 16%; adults 1% to 2%)

1% to 10%:

Cardiovascular: Bradycardia (<4%), bundle branch block (<4%), chest pain (<4%), ECG changes (<4%), facial edema (<4%), first degree atrioventricular block (<4%), hypotension (<4%), orthostatic hypotension (<4%), palpitations (<4%), prolonged Q-T interval on ECG (<4%), tachycardia (adults <4%; children <1%), hypertension (≤3%), peripheral edema (≤3%), syncope (1% to 2%)

Central nervous system: Dystonia (2% to 6%), abnormal gait (4%), pain (1% to 4%), disturbance in attention (≤4%), agitation (<4%), ataxia (<4%), depression (<4%), disturbed sleep (<4%), falling (<4%), lethargy (<4%), malaise (<4%), nervousness (<4%), orthostatic dizziness (<4%), paresthesia (<4%), seizure (<4%), tardive dyskinesia (<4%), vertigo (<4%), hypoesthesia (≤2%)

Dermatologic: Skin rash (≤8%), eczema (<4%), pruritus (<4%), skin sclerosis (<4%), xeroderma (≤3%), acne vulgaris (≤2%)

Endocrine & metabolic: Increased thirst (children ≤7%; adults <1%), weight loss (≤4%), amenorrhea (4%), decreased libido (<4%), galactorrhea (<4%), glycosuria (<4%), gynecomastia (<4%), hyperglycemia (<4%), hyperprolactinemia (<4%), increased gamma-glutamyl transferase (<4%), oligomenorrhea (<4%)

Gastrointestinal: Xerostomia (≤10%), dyspepsia (3% to 10%), sialorrhea (1% to 10%), diarrhea (≤8%), decreased appetite (≤6%), anorexia (<4%), gastritis (<4%), gastroenteritis (<4%), toothache (≤3%)

Genitourinary: Menstruation (≤4%), cystitis (<4%), ejaculatory disorder (<4%), erectile dysfunction (<4%), irregular menses (<4%), mastalgia (<4%), sexual disorder (<4%), urinary tract infection (<4%)

Hematologic & oncologic: Anemia (<4%), neutropenia (<4%)

Hepatic: Increased serum ALT (<4%), increased serum AST (<4%)

Hypersensitivity: Hypersensitivity reaction (<4%)

Infection: Infection (<4%), influenza (<4%), localized infection (<4%), subcutaneous abscess (<4%), viral infection (<4%)

Local: Induration at injection site (<4%), injection site reaction (<4%), local pain (buttock: <4%), pain at injection site (<4%), swelling at injection site (<4%)

Neuromuscular & skeletal: Limb pain (2% to 6%), dyskinesia (adults ≤6%; children <1%), back pain (≤4%), arthralgia (2% to 4%), abnormal posture (<4%), akinesia (<4%), hypokinesia (<4%), musculoskeletal chest pain (<4%), myalgia (<4%), neck pain (<4%), weakness (<4%), increased creatine phosphokinase (≤2%)

Ophthalmic: Blurred vision (2% to 7%), conjunctivitis (<4%), reduced visual acuity (<4%)

Otic: Otalgia (≤4%), otic infection (<4%)

Respiratory: Nasal congestion (≤10%), pharyngolaryngeal pain (3% to 10%), rhinitis (≤9%), respiratory tract infection (≤8%), bronchitis (<4%), dyspnea (<4%), flu-like symptoms (<4%), pharyngitis (<4%), pneumonia (<4%), sinusitis (<4%), epistaxis (≤2%), sinus congestion (≤2%)

<1%, postmarketing, and/or case reports: Abnormal erythrocytes, abscess at injection site, acariasis, agranulocytosis, alopecia, anaphylaxis, angioedema, anorgasmia, apnea, aspiration, atrial fibrillation, atrial premature contractions, blepharospasm, blunted affect, breast hypertrophy, bronchopneumonia, cellulitis, cerebral ischemia, cerebrovascular accident, cerebrovascular disease, cheilitis, chills, cholestatic hepatitis, cholinergic syndrome, cold extremities, coma, confusion, crusting of eyelid, cutaneous nodule, cyst, decreased hematocrit, decreased hemoglobin, dehydration, delirium, depression of ST segment on ECG, dermal ulcer, dermatological disease, desquamation, diabetes mellitus, diabetic coma, diabetic ketoacidosis, disruption of body temperature regulation, diverticulitis, dry eye syndrome, dysgeusia, dysphagia, dysuria, edema, eosinophilia, erythema, esophageal motility disorder, esophagitis, eye discharge, eye infection, eyelid edema, fecal incontinence, fecaloma, feeling abnormal, flushing, glaucoma, granulocytopenia, hematemesis, hematoma, hematuria, hemorrhage, hepatic failure, hepatic injury, hyperkeratosis, hyperphosphatemia, hyperthermia, hypertonia, hypertriglyceridemia, hyperuricemia, hyperventilation, hypoglycemia, hypokalemia, hyponatremia, hypoproteinemia, hypothermia, impaired consciousness, increased serum cholesterol, increased serum transaminases, intestinal obstruction, intraoperative floppy iris syndrome, inversion T wave on ECG, jaundice, joint stiffness, joint swelling, lacrimation, leukocytosis, leukopenia, leukorrhea, lip edema, loss of balance, lower respiratory tract infection, lymphadenopathy, mania, mastitis, migraine, movement disorder, myocardial infarction, myocarditis, nasal mucosa swelling, neuroleptic malignant syndrome, nystagmus, oculogyric crisis, ocular hyperemia, onychomycosis, pancreatitis, Pelger-Huet anomaly, phlebitis, photophobia, pitting edema, pituitary neoplasm, pollakiuria, polydipsia, precocious puberty, priapism, pulmonary congestion, pulmonary embolism, rales, renal insufficiency, respiratory congestion, respiratory distress, retinal artery occlusion, retrograde ejaculation, rhabdomyolysis, rigors, sarcoidosis, seborrhea, seborrheic dermatitis of scalp, SIADH, skin discoloration, skin lesion, sleep apnea, speech disturbance, stomatitis, stridor, swelling of eye, synostosis, thrombocytopenia, thrombophlebitis, thrombotic thrombocytopenic purpura, tinnitus, tissue necrosis, tongue discoloration, tongue edema, tongue paralysis, tongue spasm, tonsillitis, torticollis, tracheobronchitis, transient ischemic attacks, unresponsive to stimuli, urinary retention, urticaria, vaginal discharge, ventricular premature contractions, ventricular tachycardia, voice disorder, water intoxication, wheezing, withdrawal syndrome, xerophthalmia

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics. Use caution with history of conduction abnormalities. Relative to other neuroleptics, risperidone has a low risk of arrhythmias (APA [Lehman 2004]).

• 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).

• Antiemetic effects: May mask toxicity of other drugs or conditions (eg, intestinal obstruction, Reyes syndrome, brain tumor) due to antiemetic effects.

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, pre-existing low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1,000/mm³.

• Cerebrovascular effects: An increased incidence of cerebrovascular effects (eg, transient ischemic attack, stroke), including fatalities, has been reported in placebo-controlled trials of risperidone for the unapproved use in elderly patients with dementia-related psychosis.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving). May be low to moderately sedating in comparison with other antipsychotics (Richelson 1999); dose-related effects have been observed.

• Dyslipidemia: Has been reported with atypical antipsychotics; risk profile may differ between agents. Compared to other antipsychotics, the risk of metabolic side effects (including dyslipidemia) with risperidone is low (Solmi 2017).

• Esophageal dysmotility/Aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (eg, Alzheimer disease), particularly in patients >75 years of age (Herzig 2017; Maddalena 2004).

• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability. Complete fall risk assessments at baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk.

• Hyperglycemia: Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. Use with caution in patients with diabetes or other disorders of glucose regulation; monitor for worsening of glucose control. Compared to other antipsychotics, the risk of metabolic side effects (including hyperglycemia) with risperidone is low (Solmi 2017).

• Hyperprolactinemia: Risperidone is associated with greater increases in prolactin levels as compared to other antipsychotic agents; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown. Risk factors for hyperprolactinemia in patients taking risperidone include female gender, younger age at onset of illness, and higher scores on the Positive and Negative Symptom Scale (PANSS). Additionally, higher doses are associated with greater elevations in prolactin concentrations (Bo 2016).

• Hypersensitivity: Hypersensitivity reactions including anaphylactic reactions and angioedema have been reported.

• Intraoperative floppy iris syndrome: Few case reports describe intraoperative floppy iris syndrome (IFIS) in patients receiving risperidone and undergoing cataract surgery (Ford 2011). Prior to cataract surgery, evaluate for prior or current risperidone use. The benefits or risks of interrupting risperidone prior to surgery have not been established; clinicians are advised to proceed with surgery cautiously.

• Neuroleptic malignant syndrome: Use may be associated with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability.

• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect (eg, concurrent medication use which may predispose to hypotension/bradycardia or presence of hypovolemia) or in those who would not tolerate transient hypotensive episodes. Use caution with history of cerebrovascular or cardiovascular disease (MI, heart failure, or ischemic disease).

• Priapism: Rare cases of priapism have been reported.

• 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.

• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects (Kwok 2005, Martinez 2002).

• Weight gain: Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Compared to other antipsychotics, the risk of weight gain with risperidone is moderate (Solmi 2017). Monitor waist circumference and BMI.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with severe cardiac disease, hemodynamic instability, prior myocardial infarction or ischemic heart disease.

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death. (APA [Reus 2016]). Risperidone is not approved for the treatment of dementia-related psychosis. Careful assessment of risk factors for stroke or existing cardiovascular morbidities is required prior to initiation.

• 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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, the American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid physical withdrawal symptoms, including anorexia, anxiety, diaphoresis, diarrhea, dizziness, dyskinesia, headache, myalgia, nausea, paresthesia, restlessness, tremulousness, and vomiting (APA [Lehman 2004]; CPA [Addington 2005]; Lambert 2007; WFSBP [Hasan 2012]). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). Additional factors such as duration of antipsychotic exposure, the indication for use, medication half-life, and risk for relapse should be considered. In schizophrenia, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. However, studies in which the medication of well-stabilized patients were discontinued indicate that 75% of patients relapse within 6 to 24 months. Indefinite maintenance antipsychotic medication is generally recommended, and especially for patients who have had multiple prior episodes or 2 episodes within 5 years (APA [Lehman 2004]).

Monitoring Parameters

Mental status; vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly); weight, height, BMI, waist circumference (baseline; repeat at 4, 8, and 12 weeks after initiating or changing therapy, then quarterly; consider switching to a different antipsychotic for a weight gain ≥5% of initial weight); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with pre-existing low WBC or history of drug-induced leukopenia/neutropenia); electrolytes, renal and liver function (annually and as clinically indicated); personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease (baseline; repeat annually); fasting plasma glucose level/HbA_1c (baseline; repeat 3 months after starting antipsychotic, then yearly); fasting lipid panel (baseline; repeat 3 months after initiation of antipsychotic; if LDL level is normal repeat at 2 to 5 year intervals or more frequently if clinical indicated); changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (at each visit for the first 12 weeks after the antipsychotic is initiated or until the dose is stable, then yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 12 months; high-risk patients every 6 months); ocular examination (yearly in patients >40 years; every 2 years in younger patients) (ADA 2004; Lehman 2004; Marder 2004).

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. In human studies, 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 or intend to 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 needed in a woman planning a pregnancy or if treatment is initiated during pregnancy, use of an agent other than risperidone is preferred (Larsen 2015).

Risperidone may cause hyperprolactinemia, which may decrease reproductive function in both males and females.

Healthcare 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://www.womensmentalhealth.org/pregnancyregistry).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience weight gain, agitation, fatigue, anxiety, nausea, vomiting, abdominal pain, diarrhea, constipation, dry mouth, increased hunger, loss of strength and energy, rhinitis, rhinorrhea, pharyngitis, headache, or insomnia. Have patient report immediately to prescriber signs of infection, severe injection site irritation, signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), suicidal ideation, severe dizziness, passing out, behavioral changes, mood changes, tremors, abnormal movements, rigidity, urinary retention, change in amount of urine passed, difficulty swallowing, difficulty speaking, difficulty focusing, seizures, vision changes, shortness of breath, drooling, enlarged breasts, sexual dysfunction, nipple discharge, amenorrhea, priapism, signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot), or signs of tardive dyskinesia (unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; and puffing cheeks) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer