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Drug overview for RISPERDAL CONSTA (risperidone microspheres):
Generic name: RISPERIDONE MICROSPHERES (riss-PAIR-ih-doan)
Drug class: Antipsychotics
Therapeutic class: Central Nervous System Agents
Risperidone has been described as an atypical or second-generation antipsychotic agent.
No enhanced Uses information available for this drug.
Generic name: RISPERIDONE MICROSPHERES (riss-PAIR-ih-doan)
Drug class: Antipsychotics
Therapeutic class: Central Nervous System Agents
Risperidone has been described as an atypical or second-generation antipsychotic agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
RISPERDAL CONSTA 25 MG VIAL
RISPERDAL CONSTA 50 MG VIAL
RISPERDAL CONSTA 37.5 MG VIAL
RISPERDAL CONSTA 12.5 MG VIAL
The following indications for RISPERDAL CONSTA (risperidone microspheres) have been approved by the FDA:
Indications:
Bipolar disorder in remission
Schizophrenia
Professional Synonyms:
Dementia praecox
Parergasia
Indications:
Bipolar disorder in remission
Schizophrenia
Professional Synonyms:
Dementia praecox
Parergasia
The following dosing information is available for RISPERDAL CONSTA (risperidone microspheres):
Risperidone has a bell-shaped dose-response curve, with therapeutic efficacy of oral dosages of 12-16 mg daily lower than that of dosages of 4-8 mg daily in adults. Because dosage information contained in the manufacturers' labeling principally is derived from early clinical studies of the drug in patients not typical of the general population of patients treated in the community (i.e., in hospitalized, chronically ill schizophrenic patients accustomed to high-dose antipsychotic therapies), dosage of risperidone should be individualized according to the patient's response and tolerance. Clinicians also may consider consulting published protocols for specific dosage information, particularly in geriatric or younger patients, and in those experiencing their first psychotic episode.
The manufacturers' labeling states that the initial oral dosage of risperidone for the treatment of schizophrenia in adults is 2 mg daily (given as either 2 mg once daily or 1 mg twice daily). The dosage may be increased in increments of 1-2 mg daily at intervals of 24 hours or greater, as tolerated, up to a target dosage of 4-8 mg daily (administered once daily or in 2 equally divided doses). The manufacturers state that slower dosage titration may be appropriate in certain patients.
Evidence from open-labeled studies and clinical experience with the drug indicate that an initial dosage of 1-2 mg daily, with dosage increases in increments of 0.5-1 mg daily titrated over 6-7 days, as tolerated, to a target dosage of 4 mg daily may be appropriate for the management of schizophrenia in most otherwise healthy adult patients. Lower initial dosages (e.g., 1 mg daily) and slower dosage titrations to an initial target dosage of 2 mg daily may be appropriate for younger patients and in those being treated for their first psychotic episode; dosage may then be titrated up to 4 mg daily depending on clinical response at the lower dosage and adverse neurologic effects.
Such patients appear to benefit optimally from a risperidone dosage of 1-3 mg daily. A substantial number of patients being treated for their first psychotic episode start to develop extrapyramidal symptoms once dosages are increased above 2 mg daily. Dosage reductions should be considered in any patient who develops extrapyramidal symptoms.
While antipsychotic efficacy has been established in clinical trials at oral risperidone dosages ranging from 4-16 mg daily, the manufacturers and some clinicians state that dosages exceeding 6 mg daily, when given in 2 divided doses, did not result in further improvement but were associated with increases in some adverse effects, including extrapyramidal manifestations. Therefore, the manufacturers state that dosages exceeding 6 mg (in 2 divided doses) daily generally are not recommended and those exceeding 16 mg daily have not been evaluated for safety. In a single study of once-daily dosing, efficacy results generally were stronger for 8 mg than for 4 mg.
For the treatment of schizophrenia in adolescents 13-17 years of age, the manufacturer recommends an initial oral risperidone dosage of 0.5 mg once daily in the morning or evening. Dosage adjustments may be made in increments of 0.5
or 1 mg daily at intervals of 24 hours or greater, as tolerated, up to the recommended dosage of 3 mg daily. While antipsychotic efficacy in adolescents has been demonstrated in clinical trials at oral dosages ranging from 1-6 mg daily, no additional benefit was observed with dosages exceeding 3 mg daily and higher dosages were associated with increased adverse effects. Dosages exceeding 6 mg daily in adolescents have not been evaluated in clinical studies.
Pediatric patients who experience persistent somnolence may benefit from twice-daily administration of the drug in 2 equally divided doses.
The manufacturers state that there are no systematically collected data that specifically address switching from other antipsychotic agents to risperidone or concomitant administration with other antipsychotic agents. The first risperidone dose should be administered in place of the next scheduled parenteral antipsychotic dose in schizophrenic patients being switched from long-acting (depot) parenteral antipsychotic therapy to oral risperidone therapy.
The optimum duration of oral risperidone therapy currently is not known, but maintenance therapy with risperidone 2-8 mg daily has been shown to be effective in adults for up to 2 years. The manufacturers state that patients responding to risperidone therapy should generally continue to receive therapy at their effective dosage beyond the acute response. Patients should be reassessed periodically to determine the need for continued therapy with the drug.
If risperidone therapy is reinitiated after a drug-free period, the manufacturers recommend that the appropriate recommended schedule of careful dosage titration be employed.
The American Psychiatric Association (APA) states that prudent long-term treatment options in adults with schizophrenia with remitted first episodes or multiple episodes include either indefinite maintenance therapy or gradual discontinuance of the antipsychotic agent with close follow-up and a plan to reinstitute treatment upon symptom recurrence. Discontinuance of antipsychotic therapy should be considered only after a period of at least 1 year of symptom remission or optimal response while receiving the antipsychotic agent. In patients who have had multiple previous psychotic episodes or 2 psychotic episodes within 5 years, indefinite maintenance antipsychotic treatment is recommended.
For the management of schizophrenia in adults, the recommended dosage of extended-release risperidone injection is 25 mg administered by deep IM injection into the deltoid or gluteal area every 2 weeks. The manufacturer recommends that patients first receive oral risperidone to establish tolerability of the drug before the extended-release risperidone injection is used. To ensure that adequate plasma antipsychotic concentrations are maintained prior to the main release of risperidone from the injection site, therapy with oral risperidone or another oral antipsychotic agent (e.g., for patients being switched from other oral antipsychotic therapy to IM risperidone) should be given with the first IM injection of risperidone and continued for 3 weeks, then discontinued.
The need for continuing any concomitant therapy for managing extrapyramidal manifestations should be periodically reevaluated.
Some patients not responding to the 25-mg dosage may benefit from increasing the IM dosage to 37.5 or 50 mg every 2 weeks. However, the dosage should not be increased more frequently than every 4 weeks, and clinical effects of the increased dosage should not be expected earlier than 3 weeks after the first injection of the higher dosage.
The maximum IM dosage should not exceed 50 mg every 2 weeks since higher dosages were associated with an increased incidence of adverse effects, but no additional clinical benefit was observed.
In some patients, an initial risperidone dosage of 12.5 mg IM every 2 weeks and maintenance dosages as low as 12.5 mg every 2 weeks may be appropriate (e.g., patients with hepatic or renal impairment, patients who are receiving concurrent therapy with other drugs that increase plasma risperidone concentrations, patients with a history of poor tolerability to psychotropic drugs); however, efficacy of the 12.5
mg every 2 weeks dosage has not been evaluated in clinical trials.
Although no controlled studies have been conducted to establish the optimum duration of IM risperidone therapy in patients with schizophrenia, oral risperidone has been shown to be effective in delaying time to relapse with longer-term use. It is recommended that responding patients be continued on treatment with IM risperidone at the lowest dosage needed. Patients should periodically be reassessed to determine the need for continued treatment.
If therapy with IM risperidone is reinitiated after a drug-free period, oral risperidone (or another oral antipsychotic agent) should again be administered initially for supplementation.
For the management of acute manic or mixed episodes associated with bipolar I disorder in adults, either as monotherapy or as adjunctive therapy with lithium or valproate, the recommended initial oral dosage of risperidone is 2-3 mg given once daily. Dosage may be increased or decreased by 1 mg daily at intervals of not less than 24 hours, reflecting the procedures in the placebo-controlled trials. In these trials, the short-term (i.e., 3-week) antimanic efficacy of risperidone was demonstrated in a flexible dosage ranging from 1 to 6 mg daily.
Safety of dosages exceeding 6 mg daily has not been established.
For the treatment of acute manic or mixed episodes associated with bipolar I disorder in children and adolescents 10-17 years of age, the recommended initial oral dosage of risperidone is 0.5 mg given once daily in the morning or evening. Dosage adjustments may be made in increments of 0.5-1
mg at intervals of not less than 24 hours, as tolerated, up to a target dosage of 1-2.5 mg daily. While efficacy in pediatric patients with bipolar mania has been demonstrated in clinical trials at oral dosages ranging from 0.5-6
mg daily, no additional benefit was observed with dosages exceeding 2.5 mg daily and higher dosages were associated with increased adverse effects. Safety and efficacy of oral dosages exceeding 6 mg daily in children and adolescents have not been evaluated in clinical studies.
Pediatric patients who experience persistent somnolence may benefit from twice-daily administration of the drug in 2 equally divided doses.
The optimum duration of risperidone therapy for bipolar disorder currently is not known. While it is generally agreed that pharmacologic treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of oral risperidone beyond 3 weeks. Therefore, the manufacturers state that clinicians who elect to use risperidone for extended periods should periodically reevaluate the long-term risks and benefits of the drug for the individual patient.
For the maintenance treatment of bipolar I disorder in adults, either as monotherapy or as adjunctive therapy with lithium or valproate, the recommended dosage of extended-release risperidone injection is 25 mg administered by deep IM injection in the deltoid or gluteal area every 2 weeks. The manufacturer recommends that patients first receive oral risperidone to establish tolerability of the drug before the extended-release risperidone injection is used. To ensure that adequate therapeutic plasma concentrations are maintained prior to the main release of risperidone from the injection site, therapy with oral risperidone or another oral antipsychotic agent (e.g., for patients being switched from other oral antipsychotic therapy to IM risperidone) should be given with the first IM injection of risperidone and continued for 3 weeks, then discontinued.
The need for continuing any concomitant therapy for managing extrapyramidal manifestations should be periodically reevaluated.
Some patients not responding to an initial IM risperidone dosage of 25 mg every 2 weeks may benefit from increasing the dosage to 37.5 or 50 mg every 2 weeks. However, the dosage should not be increased more frequently than every 4 weeks, and clinical effects of the increased dosage should not be expected earlier than 3 weeks after the first injection of the higher dosage.
Safety and efficacy of IM dosages exceeding 50 mg every 2 weeks have not been evaluated in clinical trials of risperidone in the maintenance treatment of bipolar disorder.
In some patients, an initial dosage of 12.5 mg IM every 2 weeks may be appropriate (e.g., patients with hepatic or renal impairment, patients concurrently receiving drugs that increase plasma concentrations of risperidone, or patients with a history of poor tolerability to psychotropic drugs); however, efficacy of the 12.5-mg IM dosage has not been evaluated in clinical trials.
If therapy with IM risperidone is reinitiated after a drug-free period, oral risperidone (or another oral antipsychotic agent) should again be administered initially for supplementation.
The manufacturer states that clinicians who elect to use extended-release IM risperidone for extended periods should periodically reevaluate the long-term risks and benefits of the drug for the individual patient.
Because elimination of risperidone may be reduced and the risk of adverse effects, particularly hypotension, increased in patients with renal impairment, oral risperidone therapy should be initiated at a reduced dosage of 0.5 mg twice daily in adults with severe renal impairment (creatinine clearance less than 30 mL/minute) and increased as necessary and tolerated in increments of 0.5 mg or less, administered twice daily; increases beyond a dosage level of 1.5
mg twice daily should be made at intervals of at least 7 days. Likewise, this reduced oral dosage should be employed in patients with severe hepatic impairment (Child-Pugh score 10-15) because of the risk of an increased free fraction of risperidone in such patients.
If IM risperidone is used for management of schizophrenia or bipolar disorder in adults with renal or hepatic impairment, the patient should be treated with titrated doses of oral risperidone prior to initiating treatment with the extended-release injection. The recommended starting oral risperidone dosage is 0.5 mg twice daily during the first week, which can be increased to 1 mg twice daily or 2 mg once daily during the second week.
If a dosage of at least 2 mg daily of oral risperidone is well tolerated, an IM dosage of 25 mg of the extended-release injection can be administered every 2 weeks. Alternatively, such patients may receive an initial dosage of 12.5 mg IM every 2 weeks; however, efficacy of the 12.5-mg
dosage has not been evaluated in clinical trials. Oral supplementation should be continued for 3 weeks after the first injection until the main release of risperidone from the injection site has begun. In some patients, slower titration may be medically appropriate.
Adjustment of risperidone dosage may be necessary in patients receiving concomitant therapy with cytochrome P-450 (CYP) enzyme inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin) or CYP2D6 inhibitors (e.g., fluoxetine, paroxetine). When risperidone is used concomitantly with a CYP enzyme inducer (e.g., carbamazepine), the manufacturers recommend that the dosage of oral risperidone be increased, up to double the patient's usual dosage.
In patients receiving IM risperidone, an increase in the IM dosage or addition of oral risperidone may be considered when used concomitantly with a CYP enzyme inducer.
A decrease in the dosage of oral or IM risperidone may be necessary when the CYP enzyme inducer is discontinued.
When oral risperidone is used concomitantly with fluoxetine or paroxetine (CYP2D6 inhibitors), the manufacturers recommend decreasing the dosage of risperidone and not exceeding 8 mg daily in adults. If oral risperidone is initiated in patients receiving fluoxetine or paroxetine, risperidone should be titrated slowly. When fluoxetine or paroxetine is discontinued, an increase in the dosage of risperidone may be necessary.
If fluoxetine or paroxetine is initiated in patients receiving IM risperidone, a dosage reduction may be considered; dosage of IM risperidone may be reduced 2-4 weeks before initiating fluoxetine or paroxetine. If fluoxetine or paroxetine is initiated in patients receiving IM risperidone 25 mg every 2 weeks, the manufacturer recommends continuing 25 mg every 2 weeks; dosage reduction to 12.5 mg every 2 weeks or interruption of therapy may be necessary based on clinical judgment.
In patients already receiving fluoxetine or paroxetine, IM risperidone may be initiated at a dosage of 12.5 mg every 2 weeks; however, efficacy of the 12.5-mg dosage has not been evaluated in clinical trials.
The manufacturers' labeling states that the initial oral dosage of risperidone for the treatment of schizophrenia in adults is 2 mg daily (given as either 2 mg once daily or 1 mg twice daily). The dosage may be increased in increments of 1-2 mg daily at intervals of 24 hours or greater, as tolerated, up to a target dosage of 4-8 mg daily (administered once daily or in 2 equally divided doses). The manufacturers state that slower dosage titration may be appropriate in certain patients.
Evidence from open-labeled studies and clinical experience with the drug indicate that an initial dosage of 1-2 mg daily, with dosage increases in increments of 0.5-1 mg daily titrated over 6-7 days, as tolerated, to a target dosage of 4 mg daily may be appropriate for the management of schizophrenia in most otherwise healthy adult patients. Lower initial dosages (e.g., 1 mg daily) and slower dosage titrations to an initial target dosage of 2 mg daily may be appropriate for younger patients and in those being treated for their first psychotic episode; dosage may then be titrated up to 4 mg daily depending on clinical response at the lower dosage and adverse neurologic effects.
Such patients appear to benefit optimally from a risperidone dosage of 1-3 mg daily. A substantial number of patients being treated for their first psychotic episode start to develop extrapyramidal symptoms once dosages are increased above 2 mg daily. Dosage reductions should be considered in any patient who develops extrapyramidal symptoms.
While antipsychotic efficacy has been established in clinical trials at oral risperidone dosages ranging from 4-16 mg daily, the manufacturers and some clinicians state that dosages exceeding 6 mg daily, when given in 2 divided doses, did not result in further improvement but were associated with increases in some adverse effects, including extrapyramidal manifestations. Therefore, the manufacturers state that dosages exceeding 6 mg (in 2 divided doses) daily generally are not recommended and those exceeding 16 mg daily have not been evaluated for safety. In a single study of once-daily dosing, efficacy results generally were stronger for 8 mg than for 4 mg.
For the treatment of schizophrenia in adolescents 13-17 years of age, the manufacturer recommends an initial oral risperidone dosage of 0.5 mg once daily in the morning or evening. Dosage adjustments may be made in increments of 0.5
or 1 mg daily at intervals of 24 hours or greater, as tolerated, up to the recommended dosage of 3 mg daily. While antipsychotic efficacy in adolescents has been demonstrated in clinical trials at oral dosages ranging from 1-6 mg daily, no additional benefit was observed with dosages exceeding 3 mg daily and higher dosages were associated with increased adverse effects. Dosages exceeding 6 mg daily in adolescents have not been evaluated in clinical studies.
Pediatric patients who experience persistent somnolence may benefit from twice-daily administration of the drug in 2 equally divided doses.
The manufacturers state that there are no systematically collected data that specifically address switching from other antipsychotic agents to risperidone or concomitant administration with other antipsychotic agents. The first risperidone dose should be administered in place of the next scheduled parenteral antipsychotic dose in schizophrenic patients being switched from long-acting (depot) parenteral antipsychotic therapy to oral risperidone therapy.
The optimum duration of oral risperidone therapy currently is not known, but maintenance therapy with risperidone 2-8 mg daily has been shown to be effective in adults for up to 2 years. The manufacturers state that patients responding to risperidone therapy should generally continue to receive therapy at their effective dosage beyond the acute response. Patients should be reassessed periodically to determine the need for continued therapy with the drug.
If risperidone therapy is reinitiated after a drug-free period, the manufacturers recommend that the appropriate recommended schedule of careful dosage titration be employed.
The American Psychiatric Association (APA) states that prudent long-term treatment options in adults with schizophrenia with remitted first episodes or multiple episodes include either indefinite maintenance therapy or gradual discontinuance of the antipsychotic agent with close follow-up and a plan to reinstitute treatment upon symptom recurrence. Discontinuance of antipsychotic therapy should be considered only after a period of at least 1 year of symptom remission or optimal response while receiving the antipsychotic agent. In patients who have had multiple previous psychotic episodes or 2 psychotic episodes within 5 years, indefinite maintenance antipsychotic treatment is recommended.
For the management of schizophrenia in adults, the recommended dosage of extended-release risperidone injection is 25 mg administered by deep IM injection into the deltoid or gluteal area every 2 weeks. The manufacturer recommends that patients first receive oral risperidone to establish tolerability of the drug before the extended-release risperidone injection is used. To ensure that adequate plasma antipsychotic concentrations are maintained prior to the main release of risperidone from the injection site, therapy with oral risperidone or another oral antipsychotic agent (e.g., for patients being switched from other oral antipsychotic therapy to IM risperidone) should be given with the first IM injection of risperidone and continued for 3 weeks, then discontinued.
The need for continuing any concomitant therapy for managing extrapyramidal manifestations should be periodically reevaluated.
Some patients not responding to the 25-mg dosage may benefit from increasing the IM dosage to 37.5 or 50 mg every 2 weeks. However, the dosage should not be increased more frequently than every 4 weeks, and clinical effects of the increased dosage should not be expected earlier than 3 weeks after the first injection of the higher dosage.
The maximum IM dosage should not exceed 50 mg every 2 weeks since higher dosages were associated with an increased incidence of adverse effects, but no additional clinical benefit was observed.
In some patients, an initial risperidone dosage of 12.5 mg IM every 2 weeks and maintenance dosages as low as 12.5 mg every 2 weeks may be appropriate (e.g., patients with hepatic or renal impairment, patients who are receiving concurrent therapy with other drugs that increase plasma risperidone concentrations, patients with a history of poor tolerability to psychotropic drugs); however, efficacy of the 12.5
mg every 2 weeks dosage has not been evaluated in clinical trials.
Although no controlled studies have been conducted to establish the optimum duration of IM risperidone therapy in patients with schizophrenia, oral risperidone has been shown to be effective in delaying time to relapse with longer-term use. It is recommended that responding patients be continued on treatment with IM risperidone at the lowest dosage needed. Patients should periodically be reassessed to determine the need for continued treatment.
If therapy with IM risperidone is reinitiated after a drug-free period, oral risperidone (or another oral antipsychotic agent) should again be administered initially for supplementation.
For the management of acute manic or mixed episodes associated with bipolar I disorder in adults, either as monotherapy or as adjunctive therapy with lithium or valproate, the recommended initial oral dosage of risperidone is 2-3 mg given once daily. Dosage may be increased or decreased by 1 mg daily at intervals of not less than 24 hours, reflecting the procedures in the placebo-controlled trials. In these trials, the short-term (i.e., 3-week) antimanic efficacy of risperidone was demonstrated in a flexible dosage ranging from 1 to 6 mg daily.
Safety of dosages exceeding 6 mg daily has not been established.
For the treatment of acute manic or mixed episodes associated with bipolar I disorder in children and adolescents 10-17 years of age, the recommended initial oral dosage of risperidone is 0.5 mg given once daily in the morning or evening. Dosage adjustments may be made in increments of 0.5-1
mg at intervals of not less than 24 hours, as tolerated, up to a target dosage of 1-2.5 mg daily. While efficacy in pediatric patients with bipolar mania has been demonstrated in clinical trials at oral dosages ranging from 0.5-6
mg daily, no additional benefit was observed with dosages exceeding 2.5 mg daily and higher dosages were associated with increased adverse effects. Safety and efficacy of oral dosages exceeding 6 mg daily in children and adolescents have not been evaluated in clinical studies.
Pediatric patients who experience persistent somnolence may benefit from twice-daily administration of the drug in 2 equally divided doses.
The optimum duration of risperidone therapy for bipolar disorder currently is not known. While it is generally agreed that pharmacologic treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of oral risperidone beyond 3 weeks. Therefore, the manufacturers state that clinicians who elect to use risperidone for extended periods should periodically reevaluate the long-term risks and benefits of the drug for the individual patient.
For the maintenance treatment of bipolar I disorder in adults, either as monotherapy or as adjunctive therapy with lithium or valproate, the recommended dosage of extended-release risperidone injection is 25 mg administered by deep IM injection in the deltoid or gluteal area every 2 weeks. The manufacturer recommends that patients first receive oral risperidone to establish tolerability of the drug before the extended-release risperidone injection is used. To ensure that adequate therapeutic plasma concentrations are maintained prior to the main release of risperidone from the injection site, therapy with oral risperidone or another oral antipsychotic agent (e.g., for patients being switched from other oral antipsychotic therapy to IM risperidone) should be given with the first IM injection of risperidone and continued for 3 weeks, then discontinued.
The need for continuing any concomitant therapy for managing extrapyramidal manifestations should be periodically reevaluated.
Some patients not responding to an initial IM risperidone dosage of 25 mg every 2 weeks may benefit from increasing the dosage to 37.5 or 50 mg every 2 weeks. However, the dosage should not be increased more frequently than every 4 weeks, and clinical effects of the increased dosage should not be expected earlier than 3 weeks after the first injection of the higher dosage.
Safety and efficacy of IM dosages exceeding 50 mg every 2 weeks have not been evaluated in clinical trials of risperidone in the maintenance treatment of bipolar disorder.
In some patients, an initial dosage of 12.5 mg IM every 2 weeks may be appropriate (e.g., patients with hepatic or renal impairment, patients concurrently receiving drugs that increase plasma concentrations of risperidone, or patients with a history of poor tolerability to psychotropic drugs); however, efficacy of the 12.5-mg IM dosage has not been evaluated in clinical trials.
If therapy with IM risperidone is reinitiated after a drug-free period, oral risperidone (or another oral antipsychotic agent) should again be administered initially for supplementation.
The manufacturer states that clinicians who elect to use extended-release IM risperidone for extended periods should periodically reevaluate the long-term risks and benefits of the drug for the individual patient.
Because elimination of risperidone may be reduced and the risk of adverse effects, particularly hypotension, increased in patients with renal impairment, oral risperidone therapy should be initiated at a reduced dosage of 0.5 mg twice daily in adults with severe renal impairment (creatinine clearance less than 30 mL/minute) and increased as necessary and tolerated in increments of 0.5 mg or less, administered twice daily; increases beyond a dosage level of 1.5
mg twice daily should be made at intervals of at least 7 days. Likewise, this reduced oral dosage should be employed in patients with severe hepatic impairment (Child-Pugh score 10-15) because of the risk of an increased free fraction of risperidone in such patients.
If IM risperidone is used for management of schizophrenia or bipolar disorder in adults with renal or hepatic impairment, the patient should be treated with titrated doses of oral risperidone prior to initiating treatment with the extended-release injection. The recommended starting oral risperidone dosage is 0.5 mg twice daily during the first week, which can be increased to 1 mg twice daily or 2 mg once daily during the second week.
If a dosage of at least 2 mg daily of oral risperidone is well tolerated, an IM dosage of 25 mg of the extended-release injection can be administered every 2 weeks. Alternatively, such patients may receive an initial dosage of 12.5 mg IM every 2 weeks; however, efficacy of the 12.5-mg
dosage has not been evaluated in clinical trials. Oral supplementation should be continued for 3 weeks after the first injection until the main release of risperidone from the injection site has begun. In some patients, slower titration may be medically appropriate.
Adjustment of risperidone dosage may be necessary in patients receiving concomitant therapy with cytochrome P-450 (CYP) enzyme inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin) or CYP2D6 inhibitors (e.g., fluoxetine, paroxetine). When risperidone is used concomitantly with a CYP enzyme inducer (e.g., carbamazepine), the manufacturers recommend that the dosage of oral risperidone be increased, up to double the patient's usual dosage.
In patients receiving IM risperidone, an increase in the IM dosage or addition of oral risperidone may be considered when used concomitantly with a CYP enzyme inducer.
A decrease in the dosage of oral or IM risperidone may be necessary when the CYP enzyme inducer is discontinued.
When oral risperidone is used concomitantly with fluoxetine or paroxetine (CYP2D6 inhibitors), the manufacturers recommend decreasing the dosage of risperidone and not exceeding 8 mg daily in adults. If oral risperidone is initiated in patients receiving fluoxetine or paroxetine, risperidone should be titrated slowly. When fluoxetine or paroxetine is discontinued, an increase in the dosage of risperidone may be necessary.
If fluoxetine or paroxetine is initiated in patients receiving IM risperidone, a dosage reduction may be considered; dosage of IM risperidone may be reduced 2-4 weeks before initiating fluoxetine or paroxetine. If fluoxetine or paroxetine is initiated in patients receiving IM risperidone 25 mg every 2 weeks, the manufacturer recommends continuing 25 mg every 2 weeks; dosage reduction to 12.5 mg every 2 weeks or interruption of therapy may be necessary based on clinical judgment.
In patients already receiving fluoxetine or paroxetine, IM risperidone may be initiated at a dosage of 12.5 mg every 2 weeks; however, efficacy of the 12.5-mg dosage has not been evaluated in clinical trials.
Risperidone is administered orally or by IM injection.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| RISPERDAL CONSTA 25 MG VIAL | Maintenance | Adults inject 2 milliliters (25 mg) by intramuscular route by deep gluteal injection repeat every 2 weeks |
| RISPERDAL CONSTA 37.5 MG VIAL | Maintenance | Adults inject 2 milliliters (37.5 mg) by intramuscular route by deep gluteal injection repeat every 2 weeks |
| RISPERDAL CONSTA 50 MG VIAL | Maintenance | Adults inject 2 milliliters (50 mg) by intramuscular route by deep gluteal injection repeat every 2 weeks |
| RISPERDAL CONSTA 12.5 MG VIAL | Maintenance | Adults inject 4 milliliters (25 mg) using 2 separate injection sites by intramuscular route every 14 days by deep gluteal injection |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| RISPERIDONE ER 25 MG VIAL | Maintenance | Adults inject 2 milliliters (25 mg) by intramuscular route by deep gluteal injection repeat every 2 weeks |
| RISPERIDONE ER 37.5 MG VIAL | Maintenance | Adults inject 2 milliliters (37.5 mg) by intramuscular route by deep glutealinjection repeat every 2 weeks |
| RISPERIDONE ER 50 MG VIAL | Maintenance | Adults inject 2 milliliters (50 mg) by intramuscular route by deep gluteal injection repeat every 2 weeks |
| RISPERIDONE ER 12.5 MG VIAL | Maintenance | Adults inject 4 milliliters (25 mg) using 2 separate injection sites by intramuscular route every 14 days by deep gluteal injection |
The following drug interaction information is available for RISPERDAL CONSTA (risperidone microspheres):
There are 2 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Iomeprol/Neuroleptics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Neuroleptics may lower seizure threshold.(1) CLINICAL EFFECTS: Use of iomeprol in a patient receiving a neuroleptic may increase the risk of seizure.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of iomeprol states that neuroleptics should be discontinued 48 hours before iomeprol use. Treatment with a neuroleptic should not be resumed until 24 hours post-procedure.(1) DISCUSSION: Because neuroleptics may lower seizure threshold, neuroleptics should be discontinued 48 hours before iomeprol use. Treatment with a neuroleptic should not be resumed until 24 hours post-procedure.(1) |
IOMERON 350 |
| Selected CYP2D6 Substrates/Mavorixafor SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Mavorixafor is a strong inhibitor of CYP2D6 and is expected to inhibit the metabolism of agents through this pathway.(1) CLINICAL EFFECTS: Concurrent use of mavorixafor may result in elevated levels of and toxicity from agents metabolized by CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(2) PATIENT MANAGEMENT: The US manufacturer of mavorixafor states concurrent use with CYP2D6 substrate that are highly dependent on CYP2D6 metabolism is contraindicated.(1) DISCUSSION: Mavorixafor (400 mg) increased dextromethorphan (CYP2D6 substrate) maximum concentration (Cmax) and area-under-curve (AUC) by 6-fold and 9-fold, respectively.(1) Selected CYP2D6 substrates linked to this monograph include: aripiprazole, brexpiprazole, desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, fenfluramine, metoclopramide, methoxyphenamine, metoprolol, mexiletine, nebivolol, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, venlafaxine, and yohimbine. |
XOLREMDI |
There are 5 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Cabergoline/Selected Dopamine Blockers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Dopamine (D2) blockers such as the phenothiazines, butyrophenones, thioxanthenes and atypical antipsychotics may decrease the effects of cabergoline, a dopamine agonist.(1) CLINICAL EFFECTS: Concurrent administration of cabergoline with dopamine blockers (e.g. phenothiazines, butyrophenones, or thio xanthines) may decrease the effectiveness of cabergoline.(1) Cabergoline may decrease the effectiveness of antipsychotic treatment. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of cabergoline states cabergoline(1) should not be administered concurrently with dopamine antagonists. Avoid concurrent use when possible. If cabergoline is started in a patient receiving long term antipsychotic treatment, monitor closely for loss of antipsychotic efficacy. If an antipsychotic is required for a patient on long term cabergoline therapy, consider use of a shorter half-life, less potent dopamine (D2) blocking atypical antipsychotic (e.g. clozapine, quetiapine) and monitor closely. DISCUSSION: The manufacturer of cabergoline state that it should not be administered concurrently with dopamine antagonists. |
CABERGOLINE |
| Metoclopramide/Antipsychotics; Phenothiazines; Rivastigmine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: These agents block dopamine (D2) receptors. D2 blockade can cause extrapyramidal reactions, such acute dystonic reactions, pseudoparkinsonian tremors, akathisia, or tardive dyskinesia. Neuroleptic malignant syndrome may also occur in patients receiving D2 blockers. The risk of these adverse effects may be increased by concurrent use.(1-3) CLINICAL EFFECTS: Concurrent use may increase the risk of extrapyramidal reactions (e.g. acute dystonic reactions, pseudoparkinsonian tremors, akathisia, or tardive dyskinesia) and neuroleptic malignant syndrome. Tardive dyskinesia, which may be permanent, typically affects the facial muscles and may result in uncontrollable lip smacking, chewing, puckering of the mouth, frowning or scowling, sticking out the tongue, blinking and moving the eyes, and shaking of the arms and/or legs.(1-3) Symptoms of neuroleptic malignant syndrome include hyperpyrexia, muscle rigidity, altered mental status, an autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias), elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.(1) PREDISPOSING FACTORS: Patients with Parkinson's or Lewy Body Disease may be more likely to have extrapyramidal reactions or unmasking of their primary disease symptoms. The risk of extrapyramidal symptoms is also increased in patients on metoclopramide for longer than 12 weeks. Elderly patients, especially elderly women, and diabetics are at higher risk of developing tardive dyskinesia. Other extrapyramidal symptoms, like acute dystonia, have occurred more frequently in patients younger than 30 years old.(1) PATIENT MANAGEMENT: The concurrent use of metoclopramide and agents likely to cause extrapyramidal reactions should be avoided.(1) If concurrent use is warranted, monitor patients closely for extrapyramidal reactions and neuroleptic malignant syndrome. The manufacturer of metoclopramide says to avoid treatment with metoclopramide for longer than 12 weeks, and to use the lowest possible dose.(1) Discontinue therapy if symptoms occur. Instruct patients to seek immediate medical attention if symptoms develop. Symptoms of extrapyramidal reactions, including tardive dyskinesia, include involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of the tongue, bulbar type of speech, trismus, and/or dystonic reactions resembling tetanus/stridor/dyspnea.(3) DISCUSSION: Both metoclopramide and phenothiazines can cause extrapyramidal reactions, such as tardive dyskinesia, and neuroleptic malignant syndrome. The risk may be increased by concurrent use.(1,2) Extrapyramidal symptoms have been reported with concurrent metoclopramide and neuroleptics, prochlorperazine, and chlorpromazine.(4-6) |
GIMOTI, METOCLOPRAMIDE HCL, REGLAN |
| Opioids (Cough and Cold)/Antipsychotics; Phenothiazines SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of opioids and antipsychotics, including phenothiazine derivatives, may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids and other CNS depressants, such as antipsychotics, including phenothiazine derivatives, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Avoid prescribing opioid-including cough medications for patients taking CNS depressants such as antipsychotics, including phenothiazine derivatives.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: A nested case-control study looked at the relationship between antipsychotic use and risk of acute respiratory failure. Current use of antipsychotics was associated with a 2.33-fold increase in risk of respiratory failure compared to no use of antipsychotics. The risk was also significantly increased in patients with recent use of antipsychotics (within the past 15-30 days, OR = 1.79) and recent past use (within 31-90 days OR = 1.41). The risk increased with higher doses and longer duration of use.(4) Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
HYCODAN, HYDROCODONE-CHLORPHENIRAMNE ER, HYDROCODONE-HOMATROPINE MBR, HYDROMET, PROMETHAZINE-CODEINE, TUXARIN ER |
| Selected CYP2D6 Substrates/Panobinostat SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Panobinostat is a moderate inhibitor of CYP2D6 and is expected to inhibit the metabolism of agents through this pathway.(1) CLINICAL EFFECTS: Concurrent use of panobinostat may result in elevated levels of and toxicity from agents metabolized by CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(4) PATIENT MANAGEMENT: Avoid the concurrent use of panobinostat with agents that are sensitive CYP2D6 or CYP2D6 substrates with a narrow therapeutic index. If concurrent use is warranted, monitor patients for toxicity.(1) DISCUSSION: In a study in 14 subjects with advanced cancer, panobinostat (20 mg daily on Days 3, 5, and 8) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of dextromethorphan (60 mg) by 20-200% and 20-130%, respectively. Dextromethorphan exposures were extremely variable.(1) Selected CYP2D6 substrates linked to this monograph include: desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, methoxyphenamine, metoprolol, nebivolol, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, venlafaxine, and yohimbine. |
FARYDAK |
| Selected CYP1A2 or CYP2D6 Substrates/Givosiran SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Givosiran interferes with the first and rate-limiting step in hepatic heme biosynthesis, which may lower hepatic heme levels and decrease production and/or activity of cytochrome P450 enzymes.(1,2) CLINICAL EFFECTS: Concurrent use of givosiran may result in elevated levels of and toxicity from agents metabolized by CYP1A2 or CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(3) PATIENT MANAGEMENT: Avoid the concurrent use of givosiran with agents that are sensitive substrates of CYP1A2 or CYP2D6, or CYP1A2 or CYP2D6 substrates with a narrow therapeutic index. If concurrent use is unavoidable, decrease the dose of the CYP1A2 or CYP2D6 substrate and monitor patients for toxicity. DISCUSSION: A study of 9 patients with acute intermittent porphyria found that givosiran decreased the maximum concentration (Cmax) and area-under-curve (AUC) of caffeine (a CYP1A2 substrate) by 1.3- and 3.1-fold, respectively, compared to caffeine alone. Givosiran also decreased the Cmax and AUC of dextromethorphan (a CYP2D6 substrate) by 2- and 2.4-fold, respectively, compared to dextromethorphan alone.(1,2) Selected CYP2D6 substrates linked to this monograph include: desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, methoxyphenamine, metoprolol, nebivolol, nefazodone, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, and venlafaxine. Selected CYP1A2 substrates linked to this monograph include: agomelatine, aminophylline, rasagiline, tacrine, theophylline, tizanidine, and yohimbine. |
GIVLAARI |
There are 13 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Selected Antipsychotics/Lithium SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism of the interaction is unknown. Neurotoxicity symptoms (confusion, delirium, seizures, encephalopathy, and EEG changes) may be due to potentiation or an additive effect of the antipsychotic agent and lithium. CLINICAL EFFECTS: Concurrent use of lithium and selected antipsychotic agents may produce neurotoxic symptoms, including extrapyramidal symptoms, neuroleptic malignant syndrome, and encephalopathic syndrome. PREDISPOSING FACTORS: Large doses of either drug, pre-existing brain damage or other conditions (e.g. infection, dehydration) may increase the risk for neurotoxicity. PATIENT MANAGEMENT: Lithium and antipsychotic agents are commonly co-prescribed for the acute management of manic or mixed manic episodes associated with bipolar disorder. Concurrent use should be approached with caution. Consider additional clinical monitoring for signs and symptoms of neurotoxicity, including confusion, fever, lethargy, tremors, stupor, weakness, leukocytosis, and increased blood urea nitrogen. If signs of neurotoxicity appear, discontinuation of the antipsychotic agent may be required. The US manufacturer of lithium carbonate states concurrent use with antipsychotic agents, including chlorpromazine, clozapine, fluphenazine, haloperidol, perphenazine, risperidone, and thioridazine, should be monitored closely. Although uncommon to rare, cases of severe neurotoxicity have been reported with this combination. Monitoring plasma levels is not always beneficial in preventing neurotoxic symptoms. Patients may experience neurotoxic symptoms with plasma concentrations in the therapeutic ranges. Close monitoring for signs of neurotoxicity, EEG monitoring, adequate hydration, and electrolyte status are recommended to minimize toxic potential. DISCUSSION: Lithium and antipsychotic agents are commonly co-prescribed for the acute management of manic or mixed manic episodes associated with bipolar disorder. Several case reports have been published describing acute and irreversible neurotoxicity with the combination of lithium and antipsychotic agents, though these episodes often resemble rare serious events that can be attributed to the administration of either agent alone (e.g., delirium, dysphoria, encephalopathy, dyskinesias, neuroleptic malignant syndrome, etc.). Signs and symptoms of neurotoxicity associated with concomitant use have included confusion, fever, lethargy, tremors, stupor, weakness, leukocytosis, and increased blood urea nitrogen. Extrapyramidal effects, which in some cases were irreversible, and permanent brain damage have also been reported. Selected antipsychotics linked to this monograph include: benperidol, clozapine, haloperidol, and risperidone. |
LITHIUM CARBONATE, LITHIUM CARBONATE ER, LITHIUM CITRATE, LITHIUM CITRATE TETRAHYDRATE, LITHOBID |
| Selected Dopamine Agonists/Select Atypical Antipsychotics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Selected dopamine agonists are used to treat neurologic conditions such as Parkinson Disease (PD) or restless legs syndrome, and endocrine disorders such as hyperprolactinemia by directly or indirectly increasing dopamine concentrations at D2 receptors in the central nervous system (CNS). Antipsychotic agents counteract this effect by blocking dopamine activity at CNS D2 receptors.(1-5) CLINICAL EFFECTS: The efficacy of either agent may be decreased, leading to exacerbation of the disease being treated, e.g. Parkinson disease or a psychotic disorder. Dopamine agonists linked to this monograph are: bromocriptine, entacapone, levodopa, pergolide, pramipexole, ropinirole and rotigotine. Atypical antipsychotics linked to this monograph are: aripiprazole, asenapine, iloperidone, lumateperone, lurasidone, paliperidone, quetiapine, risperidone, ziprasidone and zotepine. PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body (DLB) disease are particularly susceptible to adverse effects of dopamine blockade by antipsychotics. PATIENT MANAGEMENT: Reassess the need for antipsychotic therapy. If psychosis or hallucinations are due to an antiparkinson agent, when possible consider reducing the dose or changing the antiparkinson agent before initiating antipsychotic therapy. In patients with PD and dementia, addition of a cholinesterase inhibitor (e.g. rivastigmine) may improve psychosis. If an antipsychotic is required, then an atypical antipsychotic should be used.(6,7) In patients with major psychotic disorders, consider reducing the dose, changing, or stopping the dopamine agonist. The US manufacturer of ropinirole recommends treatment with dopamine agonists only if potential benefits outweigh risks.(1) The US manufacturer of entacapone states it should not ordinarily be used in patients with major psychotic disorders as entacapone may lead to an exacerbation of psychosis.(4) DISCUSSION: An epidemiologic study evaluated 21,043 elderly patients with Parkinson disease to determine if recent initiation of a typical or atypical antipsychotic was associated with increased mortality. They found an adjusted odds ratio of 2.0 for death associated with atypical antipsychotics versus no antipsychotic. They found an adjusted odds ratio of 2.4 for death associated with typical versus atypical antipsychotics. The authors noted the increased mortality found with typical antipsychotics supports current treatment recommendations to use atypical antipsychotic agents in patients with Parkinson disease.(6,7) Two clozapine trials showed significant improvement in psychosis without worsening of motor symptoms. In contrast, two olanzapine trials were associated with unacceptable worsening of motor symptoms. Risperidone has also been associated with motor worsening in case reports. Quetiapine evaluations have been conflicting with several small studies showing improvement in psychotic symptoms while a more rigorous trial showed no improvement.(6) |
BROMOCRIPTINE MESYLATE, CARBIDOPA-LEVODOPA, CARBIDOPA-LEVODOPA ER, CARBIDOPA-LEVODOPA-ENTACAPONE, CREXONT, CYCLOSET, DHIVY, DUOPA, INBRIJA, LEVODOPA, MIRAPEX ER, NEUPRO, PRAMIPEXOLE DIHYDROCHLORIDE, PRAMIPEXOLE ER, ROPINIROLE ER, ROPINIROLE HCL, RYTARY, SINEMET, VYALEV |
| Opioids (Extended Release)/Antipsychotics; Phenothiazines SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of opioids and antipsychotics, including phenothiazine derivatives, may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids and other CNS depressants, such as antipsychotics, including phenothiazine derivatives, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Limit prescribing opioid analgesics with CNS depressants such as antipsychotics, including phenothiazine derivatives, to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a CNS depressant (for an indication other than epilepsy) with an opioid analgesic, prescribe a lower initial dose of the CNS depressant than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a CNS depressant, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: A nested case-control study looked at the relationship between antipsychotic use and risk of acute respiratory failure. Current use of antipsychotics was associated with a 2.33-fold increase in risk of respiratory failure compared to no use of antipsychotics. The risk was also significantly increased in patients with recent use of antipsychotics (within the past 15-30 days, OR = 1.79) and recent past use (within 31-90 days OR = 1.41). The risk increased with higher doses and longer duration of use.(4) Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
BUPRENORPHINE, BUTRANS, CONZIP, FENTANYL, HYDROCODONE BITARTRATE ER, HYDROMORPHONE ER, HYSINGLA ER, MORPHINE SULFATE ER, MS CONTIN, NUCYNTA ER, OXYCODONE HCL ER, OXYCONTIN, OXYMORPHONE HCL ER, TRAMADOL HCL ER, XTAMPZA ER |
| Slt Opioids (Immediate Release)/Antipsychotics;Phenothiazine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of opioids and antipsychotics, including phenothiazine derivatives, may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids and other CNS depressants, such as antipsychotics, including phenothiazine derivatives, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Limit prescribing opioid analgesics with CNS depressants such as antipsychotics, including phenothiazine derivatives, to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a CNS depressant (for an indication other than epilepsy) with an opioid analgesic, prescribe a lower initial dose of the CNS depressant than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a CNS depressant, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: A nested case-control study looked at the relationship between antipsychotic use and risk of acute respiratory failure. Current use of antipsychotics was associated with a 2.33-fold increase in risk of respiratory failure compared to no use of antipsychotics. The risk was also significantly increased in patients with recent use of antipsychotics (within the past 15-30 days, OR = 1.79) and recent past use (within 31-90 days OR = 1.41). The risk increased with higher doses and longer duration of use.(4) Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
APADAZ, BELBUCA, BELLADONNA-OPIUM, BENZHYDROCODONE-ACETAMINOPHEN, BUPRENORPHINE HCL, BUTORPHANOL TARTRATE, DILAUDID, DSUVIA, DURAMORPH, ENDOCET, FENTANYL CITRATE, FENTANYL CITRATE-0.9% NACL, FENTANYL CITRATE-D5W, FENTANYL CITRATE-STERILE WATER, FENTANYL CITRATE-WATER, FENTANYL-BUPIVACAINE-0.9% NACL, FENTANYL-BUPIVACAINE-NACL, FENTANYL-ROPIVACAINE-0.9% NACL, FENTANYL-ROPIVACAINE-NACL, HYDROCODONE BITARTRATE, HYDROCODONE-ACETAMINOPHEN, HYDROCODONE-IBUPROFEN, HYDROMORPHONE HCL, HYDROMORPHONE HCL-0.9% NACL, HYDROMORPHONE HCL-D5W, HYDROMORPHONE HCL-NACL, HYDROMORPHONE HCL-WATER, INFUMORPH, MITIGO, MORPHINE SULFATE, MORPHINE SULFATE-0.9% NACL, MORPHINE SULFATE-NACL, NALBUPHINE HCL, NALOCET, NUCYNTA, OLINVYK, OPIUM TINCTURE, OXYCODONE HCL, OXYCODONE HYDROCHLORIDE, OXYCODONE-ACETAMINOPHEN, OXYMORPHONE HCL, PENTAZOCINE-NALOXONE HCL, PERCOCET, PRIMLEV, PROLATE, REMIFENTANIL HCL, ROXICODONE, ROXYBOND, SUFENTANIL CITRATE, ULTIVA |
| Selected Opioids for MAT/Antipsychotics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of opioids and antipsychotics may result in additive CNS depression.(1-3) Levomethadone is an enantiomer of methadone.(4) CLINICAL EFFECTS: Concurrent use of opioids and other CNS depressants, such as antipsychotics, may result in profound sedation, respiratory depression, coma, and/or death.(1-3) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Medication assisted treatment (MAT) with buprenorphine, diacetylmorphine, or methadone is not contraindicated in patients taking CNS depressants; however, gradual tapering or decreasing to the lowest effective dose of the CNS depressant may be appropriate. Ensure that other health care providers prescribing other CNS depressants are aware of the patient's buprenorphine, diacetylmorphine, or methadone treatment.(2) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(5) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(6) DISCUSSION: A nested case-control study looked at the relationship between antipsychotic use and risk of acute respiratory failure. Current use of antipsychotics was associated with a 2.33-fold increase in risk of respiratory failure compared to no use of antipsychotics. The risk was also significantly increased in patients with recent use of antipsychotics (within the past 15-30 days, OR = 1.79) and recent past use (within 31-90 days OR = 1.41). The risk increased with higher doses and longer duration of use.(7) Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(8) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(9) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(10) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(11) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(12) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(13) |
BRIXADI, BUPRENORPHINE HCL, BUPRENORPHINE-NALOXONE, DISKETS, METHADONE HCL, METHADONE INTENSOL, METHADOSE, SUBLOCADE, SUBOXONE, ZUBSOLV |
| Meperidine (IR)/Selected Antipsychotics; Phenothiazines SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of opioids such as meperidine and antipsychotics, including phenothiazine derivatives, may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids such as meperidine and other CNS depressants, such as antipsychotics, including phenothiazine derivatives, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Limit prescribing opioid analgesics such as meperidine with CNS depressants such as antipsychotics, including phenothiazine derivatives, to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a CNS depressant (for an indication other than epilepsy) with an opioid analgesic, prescribe a lower initial dose of the CNS depressant than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a CNS depressant, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: A nested case-control study looked at the relationship between antipsychotic use and risk of acute respiratory failure. Current use of antipsychotics was associated with a 2.33-fold increase in risk of respiratory failure compared to no use of antipsychotics. The risk was also significantly increased in patients with recent use of antipsychotics (within the past 15-30 days, OR = 1.79) and recent past use (within 31-90 days OR = 1.41). The risk increased with higher doses and longer duration of use.(4) Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
DEMEROL, MEPERIDINE HCL, MEPERIDINE HCL-0.9% NACL |
| Codeine; Dihydrocodeine; Levorphanol (IR)/Risperidone SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of opioids such as codeine or levorphanol and antipsychotics such as risperidone may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids such as codeine or levorphanol and other CNS depressants, such as risperidone, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Limit prescribing opioid analgesics such as codeine or levorphanol with CNS depressants such as risperidone to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a CNS depressant (for an indication other than epilepsy) with an opioid analgesic, prescribe a lower initial dose of the CNS depressant than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a CNS depressant, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(4) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(5) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(6) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(7) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(8) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(9) |
ACETAMIN-CAFF-DIHYDROCODEINE, ACETAMINOPHEN-CODEINE, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BUTALB-ACETAMINOPH-CAFF-CODEIN, CARISOPRODOL-ASPIRIN-CODEINE, CODEINE PHOSPHATE, CODEINE SULFATE, DIHYDROCODEINE BITARTRATE, FIORICET WITH CODEINE, HYDROCODONE BITARTRATE, LEVORPHANOL TARTRATE, TREZIX |
| Methadone (non MAT)/Selected Antipsychotics; Phenothiazines SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of opioids such as methadone and antipsychotics, including phenothiazine derivatives, may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids such as methadone and other CNS depressants, such as antipsychotics, including phenothiazine derivatives, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Limit prescribing opioid analgesics such as methadone with CNS depressants such as antipsychotics, including phenothiazine derivatives, to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a CNS depressant (for an indication other than epilepsy) with an opioid analgesic, prescribe a lower initial dose of the CNS depressant than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a CNS depressant, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: A nested case-control study looked at the relationship between antipsychotic use and risk of acute respiratory failure. Current use of antipsychotics was associated with a 2.33-fold increase in risk of respiratory failure compared to no use of antipsychotics. The risk was also significantly increased in patients with recent use of antipsychotics (within the past 15-30 days, OR = 1.79) and recent past use (within 31-90 days OR = 1.41). The risk increased with higher doses and longer duration of use.(4) Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
METHADONE HCL, METHADONE HCL-0.9% NACL, METHADONE HCL-NACL |
| Tramadol (IR)/Selected Antipsychotics; Phenothiazines SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of opioids such as tramadol and antipsychotics, including phenothiazine derivatives, may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids such as tramadol and other CNS depressants, such as antipsychotics, including phenothiazine derivatives, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Limit prescribing opioid analgesics such as tramadol with CNS depressants such as antipsychotics, including phenothiazine derivatives, to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a CNS depressant (for an indication other than epilepsy) with an opioid analgesic, prescribe a lower initial dose of the CNS depressant than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a CNS depressant, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: A nested case-control study looked at the relationship between antipsychotic use and risk of acute respiratory failure. Current use of antipsychotics was associated with a 2.33-fold increase in risk of respiratory failure compared to no use of antipsychotics. The risk was also significantly increased in patients with recent use of antipsychotics (within the past 15-30 days, OR = 1.79) and recent past use (within 31-90 days OR = 1.41). The risk increased with higher doses and longer duration of use.(4) Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
QDOLO, TRAMADOL HCL, TRAMADOL HCL-ACETAMINOPHEN |
| Apomorphine/Select Atypical Antipsychotics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Apomorphine is a dopamine agonist. Antipsychotic agents counteract this effect by blocking dopamine activity at CNS D2 receptors.(1) CLINICAL EFFECTS: The efficacy of either agent may be decreased, leading to exacerbation of the disease being treated, e.g. Parkinson disease or a psychotic disorder. PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body(DLB) disease are particularly susceptible to adverse effects of dopamine blockade by antipsychotics. PATIENT MANAGEMENT: Reassess the need for antipsychotic therapy. If psychosis or hallucinations are due to an antiparkinson agent, when possible consider reducing the dose or changing the antiparkinson agent before initiating antipsychotic therapy. In patients with PD and dementia, addition of a cholinesterase inhibitor (e.g. rivastigmine) may improve psychosis. If an antipsychotic is required, then an atypical antipsychotic should be used.(2,3) The US manufacturer of apomorphine states patients with major psychotic disorders treated with neuroleptics should be treated with dopamine agonists only if the potential benefits outweigh the risks.(1) DISCUSSION: An epidemiologic study evaluated 21,043 elderly patients with Parkinson disease to determine if recent initiation of a typical or atypical antipsychotic was associated with increased mortality. They found an adjusted odds ratio of 2.0 for death associated with atypical antipsychotics versus no antipsychotic. They found an adjusted odds ratio of 2.4 for death associated with typical versus atypical antipsychotics. The authors noted the increased mortality found with typical antipsychotics supports current treatment recommendations to use atypical antipsychotic agents in patients with Parkinson disease.(2,3) Two clozapine trials showed significant improvement in psychosis without worsening of motor symptoms. In contrast, two olanzapine trials were associated with unacceptable worsening of motor symptoms. Risperidone has also been associated with motor worsening in case reports. Quetiapine evaluations have been conflicting with several small studies showing improvement in psychotic symptoms while a more rigorous trial showed no improvement.(2) |
APOKYN, APOMORPHINE HCL, ONAPGO |
| Risperidone Intramuscular Every 2 Weeks (Consta)/Strong CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong CYP3A4 inducers may increase the metabolic clearance of risperidone by CYP3A4.(1) Risperidone may inhibit the metabolism of carbamazepine.(2) CLINICAL EFFECTS: Strong CYP3A4 inducers may result in decreased levels and effectiveness of risperidone.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of extended release risperidone microspheres for injection (Risperdal Consta) recommends that patients maintained on this product be closely monitored during the first 4-8 weeks of concurrent therapy if an inducer of CYP3A4 is initiated. Patients may need a dosage increase of this product or additional oral risperidone. If the CYP3A4 inducer is discontinued, the manufacturer recommends that the dosage of risperidone should be re-evaluated and, if necessary, decreased. Patients may be placed on a lower dose between 2 to 4 weeks before the planned discontinuation of strong CYP3A4 inducers to adjust for the expected increase in risperidone concentrations. For patients treated with the recommended dose of 25 mg who are discontinuing from CYP3A4 inducers, it is recommended to continue treatment with the 25 mg dose unless clinical judgment necessitates lowering the dose to 12.5 mg or necessitates interruption of risperidone treatment. The efficacy of the 12.5 mg dose has not been investigated in clinical trials. Patients receiving carbamazepine should be closely monitored if risperidone is initiated or discontinued from concurrent therapy. The dosage of carbamazepine may need to be adjusted.(2) DISCUSSION: A study in 11 schizophrenic inpatients examined the effects of the addition of carbamazepine (200 mg twice daily) for one week to risperidone (3 mg twice daily). Concurrent carbamazepine decreased plasma concentrations of risperidone, 9-hydroxyrisperidone, and active moiety by 50%, 44%, and 45%, respectively.(3) A study compared 23 patients receiving risperidone alone to 11 patients receiving concurrent risperidone and carbamazepine. The groups were matched for sex, age, body weight, and risperidone dosage. Plasma concentrations of 9-hydroxyrisperidone and the sum of risperidone and 9-hydroxyrisperidone were significantly lower in patients receiving concurrent carbamazepine. Five subjects received risperidone with and without carbamazepine. In these patients, dose-normalized plasma risperidone and 9-hydroxyrisperidone concentrations were lower during concurrent carbamazepine.(4) A study in eight patients examined the effects of the addition of risperidone (1 mg daily) to carbamazepine (400 mg to 1200 mg daily). After two weeks of risperidone, carbamazepine levels increased 19%.(1) In a case report, a patient developed an exacerbation of psychotic symptoms four weeks after the addition of carbamazepine (800 mg daily) to his regimen. Plasma levels of risperidone and 9-hydroxyrisperidone had decreased by 77% and 63%, respectively.(5) In an open, randomized cross-over study in 10 healthy males, pretreatment with rifampin (600 mg daily for 5 days) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single oral dose of risperidone (4 mg) by 72% and 50%, respectively.(6) In a study in 10 healthy males, pretreatment with rifampin (600 mg daily for 7 days) decreased the AUC and Cmax of a single oral dose of risperidone (1 mg) by 51% and 38%, respectively. The AUC of 9-hydroxyrisperidone and the active moieties (risperidone + 9-hydroxyrisperidone) decreased by 43% and 45%, respectively. The Cmax of 9-hydroxyrisperidone and the active moieties decreased by 46% and 41%, respectively.(7) Strong CYP3A4 inducers linked to this monograph are: apalutamide, barbiturates, carbamazepine, enzalutamide, fosphenytoin, lumacaftor, mitotane, natisedine, phenytoin, primidone, rifampin, rifapentine and St. John's Wort.(8,9) |
ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EPITOL, EQUETRO, ERLEADA, FIORICET, FIORICET WITH CODEINE, FOSPHENYTOIN SODIUM, LYSODREN, MITOTANE, MYSOLINE, ORKAMBI, PENTOBARBITAL SODIUM, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, RIFADIN, RIFAMPIN, SEZABY, TEGRETOL, TEGRETOL XR, TENCON, XTANDI |
| Risperidone Intramuscular Every 2 Weeks (Consta)/Slt Strong 2D6 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong CYP2D6 inhibitors may inhibit the metabolism of risperidone by CYP2D6.(1) CLINICAL EFFECTS: Concurrent use of strong CYP2D6 inhibitors may result in elevated levels of risperidone and an increase in risperidone side effects.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving concurrent therapy with strong CYP2D6 inhibitors with risperidone should be observed for increases in risperidone side effects, including extrapyramidal and Parkinsonian symptoms. The dosage of risperidone should be re-evaluated.(1) The US manufacturer of extended release risperidone microspheres for injection (Risperdal Consta) recommends that patients maintained on the 25 mg dose of this product continue to receive the 25 mg dose when either fluoxetine or paroxetine (strong CYP2D6 inhibitors) is initiated, unless clinical judgment necessitates lowering the dose or interrupting therapy. If a decision is made to lower the dose, the dose may be lowered 2 to 4 weeks before the initiation of fluoxetine or paroxetine.(1) When initiating the product in patients maintained on fluoxetine or paroxetine, a starting dose of 12.5 mg can be considered. The efficacy of this dose has not been confirmed in clinical trials.(1) One set of authors recommended a low initial dose of paroxetine of 10 mg/day to 20 mg/day in patients receiving risperidone.(2) DISCUSSION: A study in 10 patients examined the effects of fluoxetine (20 mg daily) on risperidone (4-6 mg/day). One patient dropped out following the development of severe akathisia after one week of fluoxetine. Her risperidone levels had increased 457%. In the remaining patients, fluoxetine increased risperidone levels by 308% at two weeks and by 733% at four weeks. Levels of the active moiety increased by 75% by four weeks. During the second week of fluoxetine therapy, two patients developed Parkinsonian symptoms.(3) Fluoxetine has been shown to have no effect on 9-hydroxyrisperidone plasma concentrations.(3) A study in 3 poor metabolizer and 8 extensive metabolizers examined the effects of fluoxetine (20 mg daily) on risperidone (4-6 mg daily). Concurrent fluoxetine increased the area-under-curve (AUC) of risperidone and the active moiety by 29% and by 100%, respectively, in poor metabolizers. In extensive metabolizers, the AUC of risperidone and the active moiety increased by 70% and 41%, respectively.(4) A study in 10 patients examined the effects of paroxetine (20 mg daily) on risperidone (4-8 mg/day). After two and four weeks of concurrent therapy, risperidone concentrations increased 388% and 453%, respectively. Plasma concentrations of the active moiety increased 39.4% and 44.5% after two and four weeks of concurrent therapy, respectively. No symptoms of risperidone toxicity or change in extrapyramidal effects were noted. One patient developed Parkinsonism.(2) Paroxetine has been shown to lower 9-hydroxyrisperidone plasma concentrations by 10%.(2) Strong CYP2D6 inhibitors linked to this monograph include: dacomitinib, fluoxetine, hydroquinidine, paroxetine, quinidine, and terbinafine.(5) |
FLUOXETINE DR, FLUOXETINE HCL, NUEDEXTA, OLANZAPINE-FLUOXETINE HCL, PAROXETINE CR, PAROXETINE ER, PAROXETINE HCL, PAROXETINE MESYLATE, PAXIL, PAXIL CR, PROZAC, QUINIDINE GLUCONATE, QUINIDINE SULFATE, TERBINAFINE HCL, VIZIMPRO |
| Risperidone Intramuscular Every 2 Weeks/Bupropion SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bupropion is a strong CYP2D6 inhibitor and may inhibit the metabolism of risperidone.(1-4) Both bupropion and risperidone are known to lower the seizure threshold.(1-3) CLINICAL EFFECTS: Concurrent use may result in elevated levels and increased side effects from risperidone. Concurrent use of bupropion and risperidone may result in additive effects on the seizure threshold, increasing the risk of seizures.(1-3) PREDISPOSING FACTORS: The risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants an anorectics; a total daily dose of bupropion greater than 450 mg or single doses greater than 150 mg; rapid escalation of bupropion dosage; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antidepressants, theophylline, systemic steroids).(1,2) The risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(6) PATIENT MANAGEMENT: The concurrent use of bupropion and antipsychotics should be undertaken only with extreme caution and with low initial bupropion dosing and small gradual dosage increases.(1,2) Single doses should not exceed 150 mg.(1,2) The maximum daily dose of bupropion should not exceed 300 mg for smoking cessation(2) or 450 mg for depression.(1) Patients receiving concurrent therapy with strong CYP2D6 inhibitors with risperidone should be observed for increases in risperidone side effects, including extrapyramidal and Parkinsonian symptoms. The US manufacturer of extended release risperidone microspheres for injection (Risperdal Consta) recommends that patients maintained on the 25 mg dose of this product continue to receive the 25 mg dose when either fluoxetine or paroxetine (strong CYP2D6 inhibitors) is initiated, unless clinical judgment necessitates lowering the dose or interrupting therapy. If a decision is made to lower the dose, the dose may be lowered 2 to 4 weeks before the initiation of fluoxetine or paroxetine.(3) DISCUSSION: Because of the risk of seizure from concurrent bupropion and other agents that lower seizure threshold, the manufacturer of bupropion states that the concurrent use of bupropion and antipsychotics should be undertaken only with extreme caution and with low initial bupropion dosing and small gradual dosage increases.(1) In a study in 7 patients maintained on risperidone (doses ranged from 2 mg daily to 4 mg daily), the addition of duloxetine (60 mg daily) increased risperidone levels by 25%. The mean plasma risperidone/9-hydroxyrisperidone ratio increased 1.95-fold. One patient developed mild extrapyramidal symptoms. His risperidone level at the time was 72 ng/ml.(7) In contrast, a retrospective chart review compared 7 patients receiving concurrent risperidone and duloxetine to control patients receiving only risperidone and found no significant effect on risperidone levels.(8) A study in 10 patients examined the effects of fluoxetine (20 mg daily) on risperidone (4-6 mg/day). One patient dropped out following the development of severe akathisia after one week of fluoxetine. Her risperidone levels had increased 457%. In the remaining patients, fluoxetine increased risperidone levels by 308% at two weeks and by 733% at four weeks. Levels of the active moiety increased by 75% by four weeks. During the second week of fluoxetine therapy, two patients developed Parkinsonian symptoms.(9) Fluoxetine has been shown to have no effect on 9-hydroxyrisperidone plasma concentrations.(9) A study in 3 poor metabolizer and 8 extensive metabolizers examined the effects of fluoxetine (20 mg daily) on risperidone (4-6 mg daily). Concurrent fluoxetine increased the area-under-curve (AUC) of risperidone and the active moiety by 29% and by 100%, respectively, in poor metabolizers. In extensive metabolizers, the AUC of risperidone and the active moiety increased by 70% and 41%, respectively.(10) A study in 10 patients examined the effects of paroxetine (20 mg daily) on risperidone (4-8 mg/day). After two and four weeks of concurrent therapy, risperidone concentrations increased 388% and 453%, respectively. Plasma concentrations of the active moiety increased 39.4% and 44.5% after two and four weeks of concurrent therapy, respectively. No symptoms of risperidone toxicity or change in extrapyramidal effects were noted. One patient developed Parkinsonism.(11) Paroxetine has been shown to lower 9-hydroxyrisperidone plasma concentrations by 10%.(11) |
APLENZIN, AUVELITY, BUPROPION HCL, BUPROPION HCL SR, BUPROPION XL, CONTRAVE, FORFIVO XL, WELLBUTRIN SR, WELLBUTRIN XL |
The following contraindication information is available for RISPERDAL CONSTA (risperidone microspheres):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 2 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Neuroleptic malignant syndrome |
| Parkinsonism |
There are 22 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Acute myocardial infarction |
| Atherosclerotic cardiovascular disease |
| Cardiac arrhythmia |
| Cataract surgery |
| Cerebrovascular disorder |
| Chronic heart failure |
| Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min |
| Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Dehydration |
| Diffuse lewy body disease |
| Disease of liver |
| Hypotension |
| Hypovolemia |
| Leukopenia |
| Myocardial ischemia |
| Neutropenic disorder |
| Orthostatic hypotension |
| Rhabdomyolysis |
| Senile dementia |
| Severe hepatic disease |
| Tardive dyskinesia |
There are 14 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Acute cognitive impairment |
| Carcinoma of breast |
| Diabetes mellitus |
| Dysphagia |
| Fever |
| Hyperlipidemia |
| Hyperprolactinemia |
| Hypothermia |
| Intraoperative floppy iris syndrome |
| Metabolic syndrome x |
| Obesity |
| Predisposition to aspiration |
| Seizure disorder |
| Weight gain |
The following adverse reaction information is available for RISPERDAL CONSTA (risperidone microspheres):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 45 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acquired dystonia Akathisia Extrapyramidal disease Parkinsonism |
Hyperglycemia SIADH syndrome Tachycardia |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Accidental fall Agranulocytosis Anaphylaxis Anemia Angioedema Atrial fibrillation Bundle branch block Catatonia Cerebrovascular accident Chest pain Depression Diabetes mellitus DRESS syndrome Drug-induced psychosis Dyspnea Esophageal dysmotility Heart block Heat intolerance Hypertension Hypoglycemic disorder Hypokinesia Hypotension Hypothermia Ileus Jaundice Leukopenia Neuroleptic malignant syndrome Neutropenic disorder Pancreatitis Priapism Retinal vascular occlusion Seizure disorder Sinus bradycardia Sleep apnea Tardive dyskinesia Thrombotic thrombocytopenic purpura Urinary retention |
There are 86 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Agitation Constipation Diarrhea Dizziness Drowsy Dyspepsia Fatigue Headache disorder Increased appetite Musculoskeletal pain Nasal congestion Rhinitis Sedation Sialorrhea Skin rash Tremor Upper respiratory infection Weight gain Xerostomia |
Acne vulgaris Cough Hyperlipidemia Hypertriglyceridemia Hypoesthesia Injection site pain Injection site sequelae Insomnia Myalgia Nausea Orthostatic hypotension Pain Peripheral edema Pharyngitis Sinusitis Sore throat Toothache |
| Rare/Very Rare |
|---|
|
Acute abdominal pain Acute cognitive impairment Alopecia Amenorrhea Anorexia Anticholinergic toxicity Arthralgia Ataxia Back pain Blurred vision Complex sleep behavior Conjunctivitis Disorder of ejaculation Dry skin Dysarthria Dysgeusia Dysphagia Earache Eczema Erectile dysfunction Eyelid edema Fever Flushing Gastritis General weakness Hematoma Hyperprolactinemia Hypertonia Injection site abscess Libido changes Mastalgia Menstrual disorder Muscle weakness Neck pain Nervousness Nightmares Pain in extremities Palpitations Paresthesia Pruritus of skin Reduced visual acuity Rhinorrhea Salivary secretion disorder Sleep walking disorder Symptoms of anxiety Syncope Tinnitus Urinary incontinence Vertigo Vomiting |
The following precautions are available for RISPERDAL CONSTA (risperidone microspheres):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Reproductive studies in rats and rabbits using risperidone dosages of 0.4-6 times the maximum recommended human dosage on a mg/m2 basis have not revealed evidence of fetal malformation. However, risperidone has been shown to cross the placenta in rats, and an increased rate of stillborn rat pups occurred at dosages 1.5
times higher than the maximum recommended human dosage on a mg/m2 basis. In 3 reproductive studies in rats, there was an increase in pup deaths during the first 4 days of lactation at dosages 0.1-3 times the human dosage on a mg/m2 basis.
It is not known whether these deaths resulted from a direct effect on the fetuses or pups or to effects on the dams. In a separate reproductive study in rats, an increased number of pup deaths (at birth or by the day after birth) and a decrease in birth weight were observed in pups of dams treated with risperidone. Risperidone also appeared to impair maternal behavior, as evidenced by reduced weight gain and decreased survival (from day 1-4 of lactation) in pups born to control dams but reared by risperidone-treated dams.
Although there are no adequate and controlled studies to date in humans, one case of agenesis of the corpus callosum has been reported in an infant exposed to risperidone in utero; however, a causal relationship to risperidone therapy is unknown. Neonates exposed to antipsychotic agents, including risperidone, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, and feeding disorder in these neonates.
The majority of cases were also confounded by other factors, including concomitant use of other drugs known to be associated with withdrawal symptoms, prematurity, congenital malformations, and obstetrical and perinatal complications; however, some cases suggested that neonatal extrapyramidal symptoms and withdrawal may occur with exposure to antipsychotic agents alone. Some of the cases described time of symptom onset, which ranged from birth to one month after birth. Any neonate exhibiting extrapyramidal or withdrawal symptoms following in utero exposure to antipsychotic agents should be monitored.
Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive care unit support and prolonged hospitalization. For further information on extrapyramidal and withdrawal symptoms in neonates, see Cautions: Pregnancy, Fertility, and Lactation, in the Phenothiazines General Statement 28:16.08.24.
Risperidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The effect of risperidone on labor and delivery in humans is unknown.
times higher than the maximum recommended human dosage on a mg/m2 basis. In 3 reproductive studies in rats, there was an increase in pup deaths during the first 4 days of lactation at dosages 0.1-3 times the human dosage on a mg/m2 basis.
It is not known whether these deaths resulted from a direct effect on the fetuses or pups or to effects on the dams. In a separate reproductive study in rats, an increased number of pup deaths (at birth or by the day after birth) and a decrease in birth weight were observed in pups of dams treated with risperidone. Risperidone also appeared to impair maternal behavior, as evidenced by reduced weight gain and decreased survival (from day 1-4 of lactation) in pups born to control dams but reared by risperidone-treated dams.
Although there are no adequate and controlled studies to date in humans, one case of agenesis of the corpus callosum has been reported in an infant exposed to risperidone in utero; however, a causal relationship to risperidone therapy is unknown. Neonates exposed to antipsychotic agents, including risperidone, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, and feeding disorder in these neonates.
The majority of cases were also confounded by other factors, including concomitant use of other drugs known to be associated with withdrawal symptoms, prematurity, congenital malformations, and obstetrical and perinatal complications; however, some cases suggested that neonatal extrapyramidal symptoms and withdrawal may occur with exposure to antipsychotic agents alone. Some of the cases described time of symptom onset, which ranged from birth to one month after birth. Any neonate exhibiting extrapyramidal or withdrawal symptoms following in utero exposure to antipsychotic agents should be monitored.
Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive care unit support and prolonged hospitalization. For further information on extrapyramidal and withdrawal symptoms in neonates, see Cautions: Pregnancy, Fertility, and Lactation, in the Phenothiazines General Statement 28:16.08.24.
Risperidone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The effect of risperidone on labor and delivery in humans is unknown.
Risperidone and its principal active metabolite, 9-hydroxyrisperidone, are distributed into milk. Because of the potential for serious adverse reactions to risperidone in nursing infants, the manufacturers of oral risperidone state that a decision should be made whether to discontinue nursing or risperidone, taking into consideration the importance of the drug to the woman. The manufacturer of the long-acting risperidone injection states that women receiving IM risperidone should not breast-feed during treatment and for at least 12 weeks after the last injection.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for RISPERDAL CONSTA (risperidone microspheres):
WARNING: There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.
WARNING: There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.
The following icd codes are available for RISPERDAL CONSTA (risperidone microspheres)'s list of indications:
| Bipolar disorder in remission | |
| F31.7 | Bipolar disorder, currently in remission |
| F31.70 | Bipolar disorder, currently in remission, most recent episode unspecified |
| F31.71 | Bipolar disorder, in partial remission, most recent episode hypomanic |
| F31.72 | Bipolar disorder, in full remission, most recent episode hypomanic |
| F31.73 | Bipolar disorder, in partial remission, most recent episode manic |
| F31.74 | Bipolar disorder, in full remission, most recent episode manic |
| F31.75 | Bipolar disorder, in partial remission, most recent episode depressed |
| F31.76 | Bipolar disorder, in full remission, most recent episode depressed |
| F31.77 | Bipolar disorder, in partial remission, most recent episode mixed |
| F31.78 | Bipolar disorder, in full remission, most recent episode mixed |
| Schizophrenia | |
| F20 | Schizophrenia |
| F20.0 | Paranoid schizophrenia |
| F20.1 | Disorganized schizophrenia |
| F20.2 | Catatonic schizophrenia |
| F20.3 | Undifferentiated schizophrenia |
| F20.5 | Residual schizophrenia |
| F20.8 | Other schizophrenia |
| F20.81 | Schizophreniform disorder |
| F20.89 | Other schizophrenia |
| F20.9 | Schizophrenia, unspecified |
Formulary Reference Tool