Usual Adult Dose for Schizophrenia

Oral Formulations:

• Initial dose: 2 mg orally per day
• Titration dose: May increase in increments of 1 to 2 mg per day at interval of 24 hours or more, as tolerated.
• Maintenance dose: 2 to 8 mg orally per day
• Maximum dose: 16 mg orally per day

Oral Formulation Comments:

• May be administered orally once a day or in divided doses twice a day.
• Doses above 12 mg per day were not demonstrated to be more efficacious and were associated with more extrapyramidal symptoms and other adverse effects.
• Patients who respond to acute treatment doses should be maintained on the effective dose beyond the acute episode.
• Patients should be periodically reassessed to determine the continued need for treatment.

Long-acting IM Injection:

• Initial dose: 25 mg IM every 2 weeks
• Titration dose: May increase to 37.5 mg or 50 mg if needed; dose titration should occur no more frequently than every 4 weeks as expected drug release starts 3 weeks after injection.
• Maximum dose: 50 mg IM every 2 weeks

Long-acting IM Injection Comments:

• For patients who have never taken oral risperidone, it is recommended to establish tolerability with the oral formulation prior to initiating treatment with long acting injection.
• This formulation should be administered by a health care professional as deep IM deltoid or gluteal injection; do not administer IV.
• To ensure adequate therapeutic plasma concentrations are maintained prior to the main release phase of drug from the injection, oral risperidone (or another antipsychotic drug) should be given for 3 weeks following the first injection.
• Some patients not responding to the 25 mg dose may benefit from a 37.5 mg or 50 mg dose, and some patients who have a history of poor tolerability to psychotropic medications may benefit from a lower initial dose of 12.5 mg, however, the efficacy of the 12.5 mg dose has not been studied in clinical trials.

Use: Treatment of schizophrenia

Usual Adult Dose for Bipolar Disorder

Oral Formulations:

• Initial dose: 2 to 3 mg orally per day
• Titration dose: May increase in increments of 1 mg per day at interval of 24 hours or more, as tolerated.
• Maximum dose: 6 mg orally per day

Oral Formulation Comments:

• The effective dose range is 1 to 6 mg orally per day.
• May be administered orally once a day or in divided doses twice a day.
• Patients experiencing somnolence may benefit from twice a day dosing.
• There are no systematically obtained data to support the use of this drug in maintenance treatment.

Long-acting IM Injection:

• Initial dose: 25 mg IM every 2 weeks
• Titration dose: May increase to 37.5 mg or 50 mg if needed; dose titration should occur no more frequently than every 4 weeks as expected drug release starts 3 weeks after injection.
• Maximum dose: 50 mg IM every 2 weeks

Long-acting IM Injection Comments:

• For patients who have never taken oral risperidone, it is recommended to establish tolerability with oral formulation prior to initiating treatment with long acting injection.
• This formulation should be administered by a health care professional as deep IM deltoid or gluteal injection; do not administer IV.
• To ensure adequate therapeutic plasma concentrations are maintained prior to the main release phase of drug from the injection, oral risperidone (or another antipsychotic drug) should be given for 3 weeks following the first injection.
• Some patients not responding to the 25 mg dose may benefit from a 37.5 mg or 50 mg dose, and some patients who have a history of poor tolerability to psychotropic medications may benefit from a lower initial dose of 12.5 mg, however, the efficacy of the 12.5 mg dose has not been studied in clinical trials.

Use: As monotherapy or as adjunctive therapy with lithium or valproate for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder

Usual Geriatric Dose for Schizophrenia

Oral Formulations:

• Initial dose: 0.5 mg orally twice a day
• Titration dose: May increase in increments of 1 to 2 mg per day at interval of 24 hours or more, as tolerated.
• Maintenance dose: 2 to 8 mg orally per day
• Maximum dose: 16 mg/day

Oral Formulation Comments:

• May be administered orally once a day or in divided doses twice a day.
• Elderly patients exhibit a greater tendency to orthostatic hypotension, careful titration with monitoring of orthostatic vital signs should be considered.
• Doses above 12 mg per day were not demonstrated to be more efficacious and were associated with more extrapyramidal symptoms and other adverse effects.
• Patients who respond to acute treatment doses should be maintained on the effective dose beyond the acute episode.
• Patients should be periodically reassessed to determine the continued need for treatment.

Long-acting IM Injection:

• Initial dose: 25 mg IM every 2 weeks
• Titration dose: May increase to 37.5 mg or 50 mg if needed; dose titration should occur no more frequently than every 4 weeks as expected drug release starts 3 weeks after injection.
• Maximum dose: 50 mg IM every 2 weeks

Long-acting IM Injection Comments:

• For patients who have never taken oral risperidone, it is recommended to establish tolerability with oral formulation prior to initiating treatment with long acting injection.
• Should be administered by a health care professional as deep IM deltoid or gluteal injection; do not administer IV.
• Elderly patients exhibit a greater tendency to orthostatic hypotension, careful titration with monitoring of orthostatic vital signs should be considered.
• To ensure adequate therapeutic plasma concentrations are maintained prior to the main release phase of drug from the injection, oral risperidone (or another antipsychotic drug) should be given for 3 weeks following the first injection.
• Some patients not responding to the 25 mg dose may benefit from a 37.5 mg or 50 mg dose, and some patients who have a history of poor tolerability to psychotropic medications may benefit from a lower initial dose of 12.5 mg, however, the efficacy of the 12.5 mg dose has not been studied in clinical trials.

Use: Treatment of schizophrenia

Usual Geriatric Dose for Bipolar Disorder

Oral Formulations:

• Initial dose: 0.5 mg orally twice a day
• Titration dose: May increase in increments of 1 mg per day at interval of 24 hours or more, as tolerated.
• Maximum dose: 6 mg/day

Oral Formulation Comments:

• The effective dose range is 1 to 6 mg per day.
• May be administered orally once a day or in divided doses twice a day; patients experiencing somnolence may benefit from twice a day dosing.
• Elderly patients exhibit a greater tendency to orthostatic hypotension, careful titration with monitoring of orthostatic vital signs should be considered.
• There are no systematically obtained data to support the use of this drug in maintenance treatment.

Long-acting IM Injection:

• Initial dose: 25 mg IM every 2 weeks
• Titration dose: May increase to 37.5 mg or 50 mg if needed; dose titration should occur no more frequently than every 4 weeks as expected drug release starts 3 weeks after injection.
• Maximum dose: 50 mg IM every 2 weeks

Long-acting IM Injection Comments:

• For patients who have never taken oral risperidone, it is recommended to establish tolerability with oral formulation prior to initiating treatment with long acting injection.
• Should be administered by a health care professional as deep IM deltoid or gluteal injection; do not administer IV.
• Elderly patients exhibit a greater tendency to orthostatic hypotension, careful titration with monitoring of orthostatic vital signs should be considered.
• To ensure adequate therapeutic plasma concentrations are maintained prior to the main release phase of drug from the injection, oral risperidone (or another antipsychotic drug) should be given for 3 weeks following the first injection.
• Some patients not responding to the 25 mg dose may benefit from a 37.5 mg or 50 mg dose, and some patients who have a history of poor tolerability to psychotropic medications may benefit from a lower initial dose of 12.5 mg, however, the efficacy of the 12.5 mg dose has not been studied in clinical trials.

Use: As monotherapy or as adjunctive therapy with lithium or valproate for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder

Usual Pediatric Dose for Schizophrenia

13 years or older:

• Initial dose: 0.5 mg orally once a day
• Titration dose: May increase in increments of 0.5 mg to 1 mg per day at interval of 24 hours or more, as tolerated.
• Maintenance dose: 3 mg orally per day
• Maximum dose: 6 mg orally per day

Comments:

• May be administered orally once a day or in divided doses twice a day; patients experiencing somnolence may benefit from twice a day dosing.
• Doses greater than 6 mg per day have not been studied.
• Patients who respond to acute treatment doses should be maintained on the effective dose beyond the acute episode.
• Patients should be periodically reassessed to determine the continued need for treatment.

Use: Treatment of schizophrenia

Usual Pediatric Dose for Bipolar Disorder

10 years or older:

• Initial dose: 0.5 mg orally once a day
• Titration dose: May increase in increments of 0.5 mg to 1 mg per day at interval of 24 hours or more, as tolerated.
• Maximum dose: 6 mg orally per day

Comments:

• The effective dose range is 1 to 2.5 mg per day.
• May be administered orally once a day or in divided doses twice a day; patients experiencing somnolence may benefit from twice a day dosing.
• There are no systematically obtained data to support the use of this drug in maintenance treatment.

Use: As monotherapy or as adjunctive therapy with lithium or valproate for the treatment of acute manic or mixed episodes associated with Bipolar I Disorder

Usual Pediatric Dose for Autism

5 to 17 years:
Greater than 15 kg and less than 20 kg:

• Initial dose: 0.25 mg orally once a day
• Titration: after a minimum of 4 days, may increase to 0.5 mg per day; maintain this dose for a minimum of 14 days; subsequent dose increases may be made in increments of 0.25 mg at intervals of 2 weeks or more, as tolerated.
• Maintenance dose: Once sufficient clinical response has been achieved and maintained, healthcare providers should consider gradually reducing the dose to achieve the optimal balance of safety and efficacy.

20 kg or greater:

• Initial dose: 0.5 mg orally once a day
• Titration: After a minimum of 4 days, may increase to 1 mg per day; maintain this dose for a minimum of 14 days; subsequent dose increases in increments of 0.5 mg at intervals of 2 weeks or more, as tolerated.
• Maintenance dose: Once sufficient clinical response has been achieved and maintained, healthcare providers should consider gradually reducing the dose to achieve the optimal balance of safety and efficacy.

Comments:

• Dosing data is not available for children weighing less than 15 kg.
• The effective dose range is 0.5 to 3 mg per day.
• This drug may be administered orally once a day or in divided doses twice a day; patients experiencing somnolence may benefit from twice a day dosing.

Use: Treatment of irritability associated with autistic disorder, including symptoms of aggression towards others, deliberate self-injuriousness, temper tantrums, and quickly changing moods

Renal Dose Adjustments

Oral Formulations:
Mild to moderate renal impairment (CrCl 30 mL/min and greater): Dosage adjustment(s) may be required; however, no specific guidelines have been suggested. Caution recommended.
Severe renal impairment (CrCl less than 30 mL/min):

• Initial starting dose: 0.5 mg orally twice a day
• Titration: Increase in increments of 0.5 mg or less, administered twice a day. For doses above 1.5 mg twice a day, increase in intervals of 1 week or greater.

Long-acting IM Injection:

• If a total daily oral dose of at least 2 mg once daily is well tolerated, the long acting intramuscular formulation may be used.
• Initial dose: 25 mg every 2 weeks by deep IM deltoid or gluteal injection

Comment:

• A starting dose of 12.5 mg IM may be considered when clinical factors warrant a dose adjustment; however, the efficacy of the 12.5 mg dose has not been studied in clinical trials.

Liver Dose Adjustments

Oral Formulations:
Mild to moderate hepatic dysfunction (Child-Pugh less than 10): Dosage adjustment(s) may be required; however, no specific guidelines have been suggested. Caution recommended.
Severe hepatic dysfunction (Child-Pugh 10 to 15):

• Initial starting dose: 0.5 mg orally twice a day
• Titration: Increase in increments of 0.5 mg or less, administered twice a day. For doses above 1.5 mg twice a day, increase in intervals of 1 week or greater.

Long-acting IM Injection:

• If a total daily oral dose of at least 2 mg once daily is well tolerated, the long acting intramuscular formulation may be used.
• Initial dose: 25 mg every 2 weeks by deep IM deltoid or gluteal injection.

Comment:

• A starting dose of 12.5 mg IM may be considered when clinical factors warrant a dose adjustment; however, the efficacy of the 12.5 mg dose has not been studied in clinical trials.

Dose Adjustments

Concomitant Administration with CYP450 3A4 Inducers (e.g., carbamazepine, phenytoin, rifampin, phenobarbital):
Oral Formulations:

• Initiating inducers during treatment: The dose of this formulation may need to be increased (up to double).
• Discontinuation of inducers during treatment: Healthcare providers may need to decrease the dose of this formulation.

Long-acting IM Injection:

• Initiation of inducers during treatment: Closely monitor patients for the first 4 to 8 weeks; dose increases or the addition of oral risperidone may need to be considered.
• Discontinuation of inducers during treatment: Re-evaluate and, if needed, decrease the dose of this drug. Some patients may be placed on a lower dose of this drug 2 to 4 weeks prior to planned discontinuation of enzyme inducers.

Concomitant Administration with Fluoxetine or Paroxetine:
Oral Formulations:

• Initiating fluoxetine or paroxetine: The dose may need to be reduced; the maximum dose should not exceed 8 mg/day.
• Initiating this drug in a patient receiving fluoxetine or paroxetine: Titrate the dose of this drug slowly.
• Stopping fluoxetine or paroxetine: The dose of this formulation may need to be increased.

Long-acting IM Injection:

• Initiating fluoxetine or paroxetine: The dose should be reduced 2 to 4 weeks before the planned start of fluoxetine or paroxetine due to the delayed risperidone release from the microspheres; if already receiving the 25 mg dose, may continue with 25 mg dose unless clinical judgment necessitates lowering the dose to 12.5 mg or interrupting treatment. The efficacy of the 12.5 mg dose has not been investigated.
• The effects of stopping fluoxetine or paroxetine on the pharmacokinetics of the long-acting injection have not been studied.

Precautions

US BOXED WARNINGS:
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS:

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
• Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients.
• Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.
• Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.
• Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality.
• The extent to which the finding of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.
• This drug is not approved for the treatment of patients with dementia-related psychosis.

Safety and efficacy of long-acting IM injections in patients younger than 18 years have not been established.

Safety and efficacy of this drug in patients younger than 13 years in the treatment of schizophrenia have not been established.

Safety and efficacy of this drug in patients younger than 10 years in the treatment of bipolar disorder have not been established

Safety and efficacy of this drug in patients younger than 5 years in the treatment of autistic disorder have not been established.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration Advice:

• Oral: May take with or without food.
• Oral solution: May administer directly from calibrated pipette, or mix with noncarbonated water, coffee, orange juice, or low-fat milk; do not mix with cola or tea.
• Oral disintegrating tablets:
• With dry hands, place the disintegrating tablet on tongue and allow to disintegrate for a few seconds, then swallow with or without water.
• Do not split or chew the tablet.
• Injection:
• Should be administered by a health care professional by deep IM deltoid or gluteal injection using the appropriate enclosed safety needle.
• Do not combine 2 different dose strengths in a single administration.
• Do not administer IV.

Storage requirements:

• Oral tablets: Protect from light.
• Oral solution: Protect from light and freezing.
• Oral disintegrating tablets:
• Do not open blister package until ready to administer.
• Child resistant pouch should be torn at notch to access the blister.
• Remove tablets from blister by tearing apart at the perforations and peeling back the foil to expose the tablet; do not push tablet through foil as it may damage the tablet.
• Injection:
• Store in refrigerator and protect from light; may be unrefrigerated at temperatures not exceeding 25C for no more than 7 days.
• Once reconstituted, use immediately; chemical and physical stability has been demonstrated for 24 hours at 25C, must re-suspend prior to injection.

Reconstitution/preparation techniques: The long-acting IM injection manufacturer product information should be consulted.

General:

• Oral disintegrating tablets and oral solution formulations are bioequivalent to tablet formulations.
• For patients reinitiating treatment, follow the initial titration schedule.
• Controlled clinical trials assessing long-term use are not available; the physician who prescribes risperidone for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.
• No specific recommendations are available regarding switching from other antipsychotics or for the use of concomitant antipsychotics.

Monitoring:

• Cardiovascular: Orthostatic vital signs in at-risk patients
• Hematologic: CBC frequently during the first few months in patients with preexisting low WBC and/or a prior history of drug-induced leukopenia or neutropenia
• Metabolic: Increases in blood sugar, weight, and lipids
• Renal: Renal function monitoring in at-risk patients

Patient Advice:

• Inform patients that this drug may cause dizziness upon arising; it is best to get up slowly form a seated or lying position.
• Patients, families, and caregivers should be educated on the risks of suicidal thoughts and behaviors, as well as the risk of mania and hypomania; what to watch for and when to seek medical advice.
• This drug may impair judgment, thinking, or motor skills; have patients avoid driving or operating machinery until adverse effects are determined.
• Advise patients to speak with their healthcare provider if they are pregnant, intend to become pregnant, or are breastfeeding.
• Advise patients that this drug may cause metabolic changes such as increases in blood sugar, body weight and lipids.
• Patients should avoid excessive temperatures and dehydration.
• Patients should speak with their healthcare provider if they are taking, or plan to take any new prescription or over the counter medications because there is a potential for drug interactions; patients should be advised to avoid alcohol as it may make some side effects worse.

Frequently asked questions

• What is the difference between Perseris and Risperdal Consta?