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Drug overview for ABILIFY (aripiprazole):
Generic name: ARIPIPRAZOLE (AR-i-PIP-ra-zole)
Drug class: Antipsychotics
Therapeutic class: Central Nervous System Agents
Aripiprazole is considered an atypical or second-generation antipsychotic agent.
Aripiprazole is used orally for the symptomatic management of psychotic disorders (e.g., schizophrenia). Aripiprazole also is used orally for the treatment of bipolar I disorder, as an adjunct to antidepressants for the acute treatment of major depressive disorder, for the acute treatment of irritability associated with autistic disorder, and for the treatment of Tourette's syndrome (Gilles de la Tourette's syndrome). Short-acting (immediate-release) aripiprazole injection (Abilify(R); no longer commercially available in the US) has been used IM for the management of acute agitation in patients with bipolar disorder or schizophrenia.
Extended-release aripiprazole injection (Abilify Maintena(R)) is used IM for the treatment of schizophrenia and maintenance treatment of bipolar I disorder. Extended-release aripiprazole lauroxil injection (Aristada(R); available as prefilled syringes in 441-mg, 662-mg, 882-mg, and 1064-mg strengths) is used IM for the treatment of schizophrenia; the 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio(R)) is used IM in combination with oral aripiprazole for the initiation of extended-release aripiprazole lauroxil therapy for the treatment of schizophrenia. Aripiprazole tablets with sensor (Abilify MyCite(R)) is part of a digital ingestion tracking system intended to provide objective data on drug ingestion.
(See Tablets with Sensor under Administration: Oral Administration, in Dosage and Administration and also see Description: Aripiprazole Tablets with Sensor.) The ability of the system to improve patient compliance or help guide aripiprazole dosage adjustments has not been established. The manufacturer states that the use of Abilify MyCite(R) to track drug ingestion in ''real time'' or during an emergency is not recommended because detection of tablet ingestion may be delayed or may not occur. Abilify MyCite(R) is used orally for the treatment of schizophrenia, for the treatment of bipolar I disorder, and as an adjunct to antidepressants for the treatment of major depressive disorder.
Generic name: ARIPIPRAZOLE (AR-i-PIP-ra-zole)
Drug class: Antipsychotics
Therapeutic class: Central Nervous System Agents
Aripiprazole is considered an atypical or second-generation antipsychotic agent.
Aripiprazole is used orally for the symptomatic management of psychotic disorders (e.g., schizophrenia). Aripiprazole also is used orally for the treatment of bipolar I disorder, as an adjunct to antidepressants for the acute treatment of major depressive disorder, for the acute treatment of irritability associated with autistic disorder, and for the treatment of Tourette's syndrome (Gilles de la Tourette's syndrome). Short-acting (immediate-release) aripiprazole injection (Abilify(R); no longer commercially available in the US) has been used IM for the management of acute agitation in patients with bipolar disorder or schizophrenia.
Extended-release aripiprazole injection (Abilify Maintena(R)) is used IM for the treatment of schizophrenia and maintenance treatment of bipolar I disorder. Extended-release aripiprazole lauroxil injection (Aristada(R); available as prefilled syringes in 441-mg, 662-mg, 882-mg, and 1064-mg strengths) is used IM for the treatment of schizophrenia; the 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio(R)) is used IM in combination with oral aripiprazole for the initiation of extended-release aripiprazole lauroxil therapy for the treatment of schizophrenia. Aripiprazole tablets with sensor (Abilify MyCite(R)) is part of a digital ingestion tracking system intended to provide objective data on drug ingestion.
(See Tablets with Sensor under Administration: Oral Administration, in Dosage and Administration and also see Description: Aripiprazole Tablets with Sensor.) The ability of the system to improve patient compliance or help guide aripiprazole dosage adjustments has not been established. The manufacturer states that the use of Abilify MyCite(R) to track drug ingestion in ''real time'' or during an emergency is not recommended because detection of tablet ingestion may be delayed or may not occur. Abilify MyCite(R) is used orally for the treatment of schizophrenia, for the treatment of bipolar I disorder, and as an adjunct to antidepressants for the treatment of major depressive disorder.
DRUG IMAGES
ABILIFY 10 MG TABLET
ABILIFY 15 MG TABLET
ABILIFY 30 MG TABLET
ABILIFY 5 MG TABLET
ABILIFY 20 MG TABLET
ABILIFY 2 MG TABLET
The following indications for ABILIFY (aripiprazole) have been approved by the FDA:
Indications:
Bipolar disorder
Gilles de la Tourette syndrome
Infantile autism
Major depressive disorder treatment adjunct
Schizophrenia
Professional Synonyms:
Adjunctive treatment of major depressive disorder
Augmentation therapy for major depressive disorder
Autism
Bipolar affective disorder
Bipolar affective illness
Bipolar mood disorder
Childhood autism
Combined vocal and motor tics for more than one year
Dementia praecox
Gilles de la Tourette's syndrome
Kanner's syndrome
Major depressive disorder treatment augmentation
Manic-depressive illness
Parergasia
Tourette's disorder
Tourette's syndrome
Indications:
Bipolar disorder
Gilles de la Tourette syndrome
Infantile autism
Major depressive disorder treatment adjunct
Schizophrenia
Professional Synonyms:
Adjunctive treatment of major depressive disorder
Augmentation therapy for major depressive disorder
Autism
Bipolar affective disorder
Bipolar affective illness
Bipolar mood disorder
Childhood autism
Combined vocal and motor tics for more than one year
Dementia praecox
Gilles de la Tourette's syndrome
Kanner's syndrome
Major depressive disorder treatment augmentation
Manic-depressive illness
Parergasia
Tourette's disorder
Tourette's syndrome
The following dosing information is available for ABILIFY (aripiprazole):
Aripiprazole oral solution may be given at the same dose on a mg-per-mg basis as the tablet strengths of the drug up to a dose of 25 mg. However, if the oral solution is used in patients who were receiving aripiprazole 30 mg as tablets, a dose of 25 mg of the oral solution should be used.
Conventional tablets and orally disintegrating tablets of aripiprazole are bioequivalent; therefore, dosing for the orally disintegrating tablets is the same as for the conventional tablets.
Dosage of aripiprazole lauroxil is expressed in terms of aripiprazole lauroxil.
Extended-release aripiprazole lauroxil (Aristada(R)) doses of 441, 662, 882, and 1064 mg correspond to aripiprazole doses of 300, 450, 600, and 724 mg, respectively.
For the management of schizophrenia in adults, the recommended initial and target dosage of aripiprazole is 10 or 15 mg orally once daily. Although dosages ranging from 10-30 mg daily administered as conventional tablets were effective in clinical trials, the manufacturer states that dosages exceeding 10-15 mg daily did not result in greater efficacy. The maximum recommended dosage is 30 mg daily.
Because steady-state plasma concentrations of aripiprazole and dehydro-aripiprazole, its active metabolite, may not be attained for 2 weeks, dosage adjustments generally should be made at intervals of not less than 2 weeks.
For the management of schizophrenia in adolescents 13-17 years of age, the recommended target dosage of aripiprazole is 10 mg orally once daily. Therapy was initiated in a dosage of 2 mg once daily in these patients, with subsequent titration to 5 mg once daily after 2 days and to the target dosage of 10 mg once daily after 2 additional days. The manufacturer recommends that any subsequent dosage increases be made in 5-mg, once-daily increments.
Although aripiprazole dosages of 10 and 30 mg once daily administered as conventional tablets have been studied in adolescents, the 30-mg daily dosage was not found to be more effective than the 10-mg daily dosage.
The optimum duration of oral aripiprazole therapy in patients with schizophrenia currently is not known, but maintenance therapy with aripiprazole 15 mg once daily as conventional tablets has been shown to be effective in preventing relapse for up to 26 weeks in adults. In addition, a combined analysis of data from 2 double-blind, multicenter studies indicates that maintenance therapy with the drug may be effective for up to 52 weeks in adults.
Although the efficacy of oral aripiprazole as maintenance therapy in pediatric patients with schizophrenia has not been systematically evaluated, the manufacturer states that such efficacy can be extrapolated from adult data in addition to comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients.
The American Psychiatric Association (APA) states that prudent long-term treatment options in patients 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.
The manufacturer states that the need for continued therapy with the drug should be reassessed periodically.
There are no systematically collected data to specifically address switching patients with schizophrenia from other antipsychotic agents to aripiprazole or concerning concomitant administration with other antipsychotic agents. Immediate discontinuance of the previous antipsychotic agent may be acceptable in some patients with schizophrenia, and more gradual discontinuance may be most appropriate for other patients. In all patients, the period of overlapping antipsychotic administration should be minimized.
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole be established prior to initiating IM therapy with extended-release aripiprazole injection (Abilify Maintena(R)). Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
For the treatment of schizophrenia in adults, the recommended dosage of extended-release aripiprazole injection (Abilify Maintena(R)) is 400 mg administered by IM injection every month (no sooner than 26 days following the previous injection). In patients experiencing adverse effects, a reduction in dosage to 300 mg every month may be considered.
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.
If a dose of extended-release aripiprazole injection is missed, the next dose should be administered as soon as possible. Supplementation with oral aripiprazole may be required depending on the time elapsed. If the second or third doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection does not exceed 5 weeks; however, if the time elapsed since the last injection exceeds 5 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection.
If the fourth or subsequent doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection does not exceed 6 weeks; however, if the time elapsed since the last injection exceeds 6 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection.
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole therapy be established prior to initiating IM therapy with extended-release aripiprazole lauroxil (Aristada(R)). Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
For the treatment of schizophrenia in adults, extended-release aripiprazole lauroxil injection (Aristada(R)) may be initiated at a dosage of 441, 662, or 882 mg every month; 882 mg every 6 weeks; or 1064 mg every 2 months by IM injection. Oral aripiprazole should be administered with the first IM injection of aripiprazole lauroxil and continued for 21 days.
For patients established on oral aripiprazole 10 mg daily, the recommended IM dosage of extended-release aripiprazole lauroxil is 441 mg every month.
For patients established on oral aripiprazole 15 mg daily, the recommended IM dosage of extended-release aripiprazole lauroxil is 662 mg every month, 882 mg every 6 weeks, or 1064 mg every 2 months.
For patients established on oral aripiprazole 20 mg or higher daily, the recommended IM dosage of extended-release aripiprazole lauroxil is 882 mg every month.
Subsequent dosage adjustments may be made if needed. If dosage adjustments are required, the manufacturer states that the pharmacokinetics and prolonged-release characteristics of extended-release aripiprazole lauroxil injection should be considered when making dosage and dosing interval adjustments.
If a dose of aripiprazole lauroxil injection is missed, the next dose should be administered as soon as possible. Supplementation with oral aripiprazole and/or a 675-mg IM dose of extended-release aripiprazole lauroxil (Aristada Initio(R)) may be required depending on the dosage and the time elapsed (see Tables 1 and 2).
Table 1. Recommended Oral Aripiprazole Supplementation Following Missed Doses of Extended-release Aripiprazole Lauroxil Injection (Aristada(R)).
Dosage of No Oral Supplement with Supplement with Patient's Last Supplementation Oral Aripiprazole Oral Aripiprazole Injection Required for 7 Days for 21 Days 441 mg monthly <=6 weeks since >6 and <=7 weeks >7 weeks since last injection since last last injection injection 662 mg monthly <=8 weeks since >8 and <=12 weeks >12 weeks since last injection since last last injection injection 882 mg monthly <=8 weeks since >8 and <=12 weeks >12 weeks since last injection since last last injection injection 882 mg every 6 <=8 weeks since >8 and <=12 weeks >12 weeks since weeks last injection since last last injection injection 1064 mg every 2 <=10 weeks since >10 and <=12 >12 weeks since months last injection weeks since last last injection injection
Dosage of oral aripiprazole supplementation should be same as when patient began extended-release aripiprazole lauroxil therapy.
Table 2. Recommended IM Aripiprazole Lauroxil Supplementation with Aristada Initio(R) Following Missed Doses of Extended-release Aripiprazole Lauroxil Injection (Aristada(R)).
Dose of Patient's No IM Supplement with a Reinitiate with a Last Injection Supplementation Single 675-mg IM Single 675-mg IM Required Dose of Dose of Aripiprazole Aripiprazole Lauroxil Lauroxil and a Single 30-mg Dose of Oral Aripiprazole 441 mg <=6 weeks since >6 and <=7 weeks >7 weeks since last injection since last last injection injection 662 mg <=8 weeks since >8 and <=12 weeks >12 weeks since last injection since last last injection injection 882 mg <=8 weeks since >8 and <=12 weeks >12 weeks since last injection since last last injection injection 1064 mg <=10 weeks since >10 and <=12 >12 weeks since last injection weeks since last last injection injection
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole therapy be established prior to initiating IM therapy with extended-release aripiprazole lauroxil (Aristada Initio(R)). Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
The 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio(R)) is only used as a single dose to initiate aripiprazole lauroxil therapy or as a single dose to reinitiate therapy following a missed dose of extended-release aripiprazole lauroxil injection (Aristada(R)). The 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio(R)) is not used for repeated dosing of the drug.
For the initiation of aripiprazole lauroxil therapy for the treatment of schizophrenia in adults and after establishing tolerability with oral aripiprazole, the first IM injection of aripiprazole lauroxil (Aristada(R); 441 mg, 662 mg, 882 mg, or 1064 mg) may be administered in conjunction with both one 675-mg IM injection of aripiprazole lauroxil (Aristada Initio(R)) into the deltoid or gluteal muscle (this dosage is equivalent to 459 mg of aripiprazole) and one 30-mg dose of oral aripiprazole.
The first dosage of aripiprazole lauroxil (Aristada(R)) may be administered on the same day as Aristada Initio(R) or up to 10 days thereafter. Clinicians should avoid injecting both IM formulations of aripiprazole lauroxil concurrently into the same deltoid or gluteal muscle.
For re-initiation of aripiprazole lauroxil (Aristada(R)) therapy following a missed dose, the next injection of aripiprazole lauroxil (Aristada(R)) should be administered as soon as possible. Depending on the time elapsed since the last Aristada(R) injection, the next Aristada(R) injection may be supplemented as recommended in Table 2.
For the acute management of manic and mixed episodes associated with bipolar I disorder in adults, the recommended initial aripiprazole dosage is 15 mg given orally once daily as monotherapy or 10-15 mg given orally once daily as adjunctive therapy with lithium or valproate. The recommended target dosage of aripiprazole is 15 mg daily whether the drug is given as monotherapy or as adjunctive therapy with lithium or valproate. Based on clinical response, the dosage can be increased to the maximum recommended dosage of 30 mg daily.
Safety of aripiprazole dosages exceeding 30 mg daily has not been established in clinical trials.
For the acute management of manic and mixed episodes associated with bipolar I disorder in pediatric patients 10-17 years of age, the recommended initial aripiprazole dosage when given as monotherapy is 2 mg orally once daily, with subsequent titration to 5 mg once daily after 2 days and to the target dosage of 10 mg once daily after 2 additional days. The recommended dosage when aripiprazole is given as adjunctive therapy with lithium or valproate is the same as that for monotherapy. Subsequent increases in the daily dosage of aripiprazole, if necessary, should be made in 5-mg increments.
In pediatric clinical studies, oral aripiprazole dosages of 10 and 30 mg daily were effective.
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole be established prior to initiating IM therapy with extended-release aripiprazole injection (Abilify Maintena(R)). Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
For the maintenance treatment of bipolar I disorder in adults, the recommended dosage of extended-release aripiprazole injection (Abilify Maintena(R)) is 400 mg administered by IM injection every month (no sooner than 26 days following the previous injection). In patients experiencing adverse effects, a reduction in dosage to 300 mg every month may be considered.
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.
If a dose of extended-release aripiprazole injection is missed, the next dose should be administered as soon as possible. Supplementation with oral aripiprazole may be required depending on the time elapsed. If the second or third doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection does not exceed 5 weeks; however, if the time elapsed since the last injection exceeds 5 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection. If the fourth or subsequent doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection does not exceed 6 weeks; however, if the time elapsed since the last injection exceeds 6 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection.
Conventional tablets and orally disintegrating tablets of aripiprazole are bioequivalent; therefore, dosing for the orally disintegrating tablets is the same as for the conventional tablets.
Dosage of aripiprazole lauroxil is expressed in terms of aripiprazole lauroxil.
Extended-release aripiprazole lauroxil (Aristada(R)) doses of 441, 662, 882, and 1064 mg correspond to aripiprazole doses of 300, 450, 600, and 724 mg, respectively.
For the management of schizophrenia in adults, the recommended initial and target dosage of aripiprazole is 10 or 15 mg orally once daily. Although dosages ranging from 10-30 mg daily administered as conventional tablets were effective in clinical trials, the manufacturer states that dosages exceeding 10-15 mg daily did not result in greater efficacy. The maximum recommended dosage is 30 mg daily.
Because steady-state plasma concentrations of aripiprazole and dehydro-aripiprazole, its active metabolite, may not be attained for 2 weeks, dosage adjustments generally should be made at intervals of not less than 2 weeks.
For the management of schizophrenia in adolescents 13-17 years of age, the recommended target dosage of aripiprazole is 10 mg orally once daily. Therapy was initiated in a dosage of 2 mg once daily in these patients, with subsequent titration to 5 mg once daily after 2 days and to the target dosage of 10 mg once daily after 2 additional days. The manufacturer recommends that any subsequent dosage increases be made in 5-mg, once-daily increments.
Although aripiprazole dosages of 10 and 30 mg once daily administered as conventional tablets have been studied in adolescents, the 30-mg daily dosage was not found to be more effective than the 10-mg daily dosage.
The optimum duration of oral aripiprazole therapy in patients with schizophrenia currently is not known, but maintenance therapy with aripiprazole 15 mg once daily as conventional tablets has been shown to be effective in preventing relapse for up to 26 weeks in adults. In addition, a combined analysis of data from 2 double-blind, multicenter studies indicates that maintenance therapy with the drug may be effective for up to 52 weeks in adults.
Although the efficacy of oral aripiprazole as maintenance therapy in pediatric patients with schizophrenia has not been systematically evaluated, the manufacturer states that such efficacy can be extrapolated from adult data in addition to comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients.
The American Psychiatric Association (APA) states that prudent long-term treatment options in patients 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.
The manufacturer states that the need for continued therapy with the drug should be reassessed periodically.
There are no systematically collected data to specifically address switching patients with schizophrenia from other antipsychotic agents to aripiprazole or concerning concomitant administration with other antipsychotic agents. Immediate discontinuance of the previous antipsychotic agent may be acceptable in some patients with schizophrenia, and more gradual discontinuance may be most appropriate for other patients. In all patients, the period of overlapping antipsychotic administration should be minimized.
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole be established prior to initiating IM therapy with extended-release aripiprazole injection (Abilify Maintena(R)). Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
For the treatment of schizophrenia in adults, the recommended dosage of extended-release aripiprazole injection (Abilify Maintena(R)) is 400 mg administered by IM injection every month (no sooner than 26 days following the previous injection). In patients experiencing adverse effects, a reduction in dosage to 300 mg every month may be considered.
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.
If a dose of extended-release aripiprazole injection is missed, the next dose should be administered as soon as possible. Supplementation with oral aripiprazole may be required depending on the time elapsed. If the second or third doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection does not exceed 5 weeks; however, if the time elapsed since the last injection exceeds 5 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection.
If the fourth or subsequent doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection does not exceed 6 weeks; however, if the time elapsed since the last injection exceeds 6 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection.
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole therapy be established prior to initiating IM therapy with extended-release aripiprazole lauroxil (Aristada(R)). Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
For the treatment of schizophrenia in adults, extended-release aripiprazole lauroxil injection (Aristada(R)) may be initiated at a dosage of 441, 662, or 882 mg every month; 882 mg every 6 weeks; or 1064 mg every 2 months by IM injection. Oral aripiprazole should be administered with the first IM injection of aripiprazole lauroxil and continued for 21 days.
For patients established on oral aripiprazole 10 mg daily, the recommended IM dosage of extended-release aripiprazole lauroxil is 441 mg every month.
For patients established on oral aripiprazole 15 mg daily, the recommended IM dosage of extended-release aripiprazole lauroxil is 662 mg every month, 882 mg every 6 weeks, or 1064 mg every 2 months.
For patients established on oral aripiprazole 20 mg or higher daily, the recommended IM dosage of extended-release aripiprazole lauroxil is 882 mg every month.
Subsequent dosage adjustments may be made if needed. If dosage adjustments are required, the manufacturer states that the pharmacokinetics and prolonged-release characteristics of extended-release aripiprazole lauroxil injection should be considered when making dosage and dosing interval adjustments.
If a dose of aripiprazole lauroxil injection is missed, the next dose should be administered as soon as possible. Supplementation with oral aripiprazole and/or a 675-mg IM dose of extended-release aripiprazole lauroxil (Aristada Initio(R)) may be required depending on the dosage and the time elapsed (see Tables 1 and 2).
Table 1. Recommended Oral Aripiprazole Supplementation Following Missed Doses of Extended-release Aripiprazole Lauroxil Injection (Aristada(R)).
Dosage of No Oral Supplement with Supplement with Patient's Last Supplementation Oral Aripiprazole Oral Aripiprazole Injection Required for 7 Days for 21 Days 441 mg monthly <=6 weeks since >6 and <=7 weeks >7 weeks since last injection since last last injection injection 662 mg monthly <=8 weeks since >8 and <=12 weeks >12 weeks since last injection since last last injection injection 882 mg monthly <=8 weeks since >8 and <=12 weeks >12 weeks since last injection since last last injection injection 882 mg every 6 <=8 weeks since >8 and <=12 weeks >12 weeks since weeks last injection since last last injection injection 1064 mg every 2 <=10 weeks since >10 and <=12 >12 weeks since months last injection weeks since last last injection injection
Dosage of oral aripiprazole supplementation should be same as when patient began extended-release aripiprazole lauroxil therapy.
Table 2. Recommended IM Aripiprazole Lauroxil Supplementation with Aristada Initio(R) Following Missed Doses of Extended-release Aripiprazole Lauroxil Injection (Aristada(R)).
Dose of Patient's No IM Supplement with a Reinitiate with a Last Injection Supplementation Single 675-mg IM Single 675-mg IM Required Dose of Dose of Aripiprazole Aripiprazole Lauroxil Lauroxil and a Single 30-mg Dose of Oral Aripiprazole 441 mg <=6 weeks since >6 and <=7 weeks >7 weeks since last injection since last last injection injection 662 mg <=8 weeks since >8 and <=12 weeks >12 weeks since last injection since last last injection injection 882 mg <=8 weeks since >8 and <=12 weeks >12 weeks since last injection since last last injection injection 1064 mg <=10 weeks since >10 and <=12 >12 weeks since last injection weeks since last last injection injection
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole therapy be established prior to initiating IM therapy with extended-release aripiprazole lauroxil (Aristada Initio(R)). Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
The 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio(R)) is only used as a single dose to initiate aripiprazole lauroxil therapy or as a single dose to reinitiate therapy following a missed dose of extended-release aripiprazole lauroxil injection (Aristada(R)). The 675-mg strength of extended-release aripiprazole lauroxil injection (Aristada Initio(R)) is not used for repeated dosing of the drug.
For the initiation of aripiprazole lauroxil therapy for the treatment of schizophrenia in adults and after establishing tolerability with oral aripiprazole, the first IM injection of aripiprazole lauroxil (Aristada(R); 441 mg, 662 mg, 882 mg, or 1064 mg) may be administered in conjunction with both one 675-mg IM injection of aripiprazole lauroxil (Aristada Initio(R)) into the deltoid or gluteal muscle (this dosage is equivalent to 459 mg of aripiprazole) and one 30-mg dose of oral aripiprazole.
The first dosage of aripiprazole lauroxil (Aristada(R)) may be administered on the same day as Aristada Initio(R) or up to 10 days thereafter. Clinicians should avoid injecting both IM formulations of aripiprazole lauroxil concurrently into the same deltoid or gluteal muscle.
For re-initiation of aripiprazole lauroxil (Aristada(R)) therapy following a missed dose, the next injection of aripiprazole lauroxil (Aristada(R)) should be administered as soon as possible. Depending on the time elapsed since the last Aristada(R) injection, the next Aristada(R) injection may be supplemented as recommended in Table 2.
For the acute management of manic and mixed episodes associated with bipolar I disorder in adults, the recommended initial aripiprazole dosage is 15 mg given orally once daily as monotherapy or 10-15 mg given orally once daily as adjunctive therapy with lithium or valproate. The recommended target dosage of aripiprazole is 15 mg daily whether the drug is given as monotherapy or as adjunctive therapy with lithium or valproate. Based on clinical response, the dosage can be increased to the maximum recommended dosage of 30 mg daily.
Safety of aripiprazole dosages exceeding 30 mg daily has not been established in clinical trials.
For the acute management of manic and mixed episodes associated with bipolar I disorder in pediatric patients 10-17 years of age, the recommended initial aripiprazole dosage when given as monotherapy is 2 mg orally once daily, with subsequent titration to 5 mg once daily after 2 days and to the target dosage of 10 mg once daily after 2 additional days. The recommended dosage when aripiprazole is given as adjunctive therapy with lithium or valproate is the same as that for monotherapy. Subsequent increases in the daily dosage of aripiprazole, if necessary, should be made in 5-mg increments.
In pediatric clinical studies, oral aripiprazole dosages of 10 and 30 mg daily were effective.
In patients who have never received aripiprazole, the manufacturer recommends that tolerability with oral aripiprazole be established prior to initiating IM therapy with extended-release aripiprazole injection (Abilify Maintena(R)). Because of the half-life of oral aripiprazole, it may take up to 2 weeks to fully assess tolerability.
For the maintenance treatment of bipolar I disorder in adults, the recommended dosage of extended-release aripiprazole injection (Abilify Maintena(R)) is 400 mg administered by IM injection every month (no sooner than 26 days following the previous injection). In patients experiencing adverse effects, a reduction in dosage to 300 mg every month may be considered.
To maintain therapeutic antipsychotic concentrations during initiation of therapy with extended-release aripiprazole injection, oral aripiprazole at a dosage of 10-20 mg daily or another oral antipsychotic agent (for patients already stable on another oral antipsychotic agent and known to tolerate aripiprazole) should be given after the first IM injection of extended-release aripiprazole and continued for 14 days.
If a dose of extended-release aripiprazole injection is missed, the next dose should be administered as soon as possible. Supplementation with oral aripiprazole may be required depending on the time elapsed. If the second or third doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection does not exceed 5 weeks; however, if the time elapsed since the last injection exceeds 5 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection. If the fourth or subsequent doses are missed, supplementation with oral aripiprazole is not required if the time elapsed since the last injection does not exceed 6 weeks; however, if the time elapsed since the last injection exceeds 6 weeks, supplementation with oral aripiprazole should be given for 14 days with the next administered injection.
Aripiprazole is administered orally or by IM injection. Aripiprazole lauroxil is administered only by IM injection. Patients receiving aripiprazole should be monitored for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment. (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| ABILIFY 2 MG TABLET | Maintenance | Adults take 1 tablet (2 mg) by oral route once daily |
| ABILIFY 5 MG TABLET | Maintenance | Adults take 1 tablet (5 mg) by oral route once daily |
| ABILIFY 10 MG TABLET | Maintenance | Adults take 1 tablet (10 mg) by oral route once daily |
| ABILIFY 15 MG TABLET | Maintenance | Adults take 1 tablet (15 mg) by oral route once daily |
| ABILIFY 20 MG TABLET | Maintenance | Adults take 1 tablet (20 mg) by oral route once daily |
| ABILIFY 30 MG TABLET | Maintenance | Adults take 1 tablet (30 mg) by oral route once daily |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| ARIPIPRAZOLE 5 MG TABLET | Maintenance | Adults take 1 tablet (5 mg) by oral route once daily |
| ARIPIPRAZOLE 2 MG TABLET | Maintenance | Adults take 1 tablet (2 mg) by oral route once daily |
| ARIPIPRAZOLE 10 MG TABLET | Maintenance | Adults take 1 tablet (10 mg) by oral route once daily |
| ARIPIPRAZOLE 15 MG TABLET | Maintenance | Adults take 1 tablet (15 mg) by oral route once daily |
| ARIPIPRAZOLE 20 MG TABLET | Maintenance | Adults take 1 tablet (20 mg) by oral route once daily |
| ARIPIPRAZOLE 30 MG TABLET | Maintenance | Adults take 1 tablet (30 mg) by oral route once daily |
The following drug interaction information is available for ABILIFY (aripiprazole):
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 4 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 |
| Selected Antipsychotics/Strong CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong CYP3A4 inducers may increase the metabolic clearance of aripiprazole(1), brexpiprazole(2), and risperidone.(3) CLINICAL EFFECTS: Strong CYP3A4 inducers may result in decreased levels and effectiveness of aripiprazole, brexpiprazole, and risperidone.(1-3) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The dose of immediate release aripiprazole should be doubled over 1-2 weeks if a CYP3A4 inducer is added to aripiprazole therapy. Additional dosage increases should be based on clinical observation of the patient. If the inducer is withdrawn from concurrent therapy, the dosage of aripiprazole should be gradually reduced to the original level over 1-2 weeks.(1) The dose of brexpiprazole should be doubled over 1-2 weeks in patients taking strong CYP3A4 inducers. If the inducer is discontinued, reduce the dosage of brexpiprazole to the original level over 1-2 weeks.(2) The US manufacturer of risperidone (Risperdal) recommends that patients increase the dose of risperidone up to double the patient's usual dose when taken concurrently with a CYP3A4 inducer. Do not exceed twice the patient's usual dose. It may be necessary to decrease the risperidone dose when the CYP3A4 inducer is discontinued.(3) DISCUSSION: The concurrent administration of carbamazepine (200 mg twice daily) with aripiprazole (30 mg daily) resulted in 70% decreases in the area-under-curve (AUC) and maximum concentration (Cmax) of both aripiprazole and dehydro-aripiprazole, its active metabolite.(1) Rifampin decreased the AUC of brexpiprazole by approximately 75%.(2) 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.(4) 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.(5) 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.(6) 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.(7) 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.(8) 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.(9,10) |
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 |
| 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 |
There are 12 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 |
|---|---|
| Aripiprazole IR/Strong CYP3A4 Inhib; Atazanavir; Darunavir SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong CYP3A4 inhibitors may inhibit the metabolism of aripiprazole.(1-2) CLINICAL EFFECTS: Concurrent administration of a strong CYP3A4 inhibitor may result in elevated levels of and toxicity from aripiprazole.(1-2) PREDISPOSING FACTORS: This interaction is expected to be more severe in patients who are CYP2D6 poor metabolizers, or who receive concomitant treatment with a strong CYP2D6 inhibitor (e.g. bupropion, fluoxetine, paroxetine, quinidine) in addition to treatment with a strong CYP3A4 inhibitor.(1-2) PATIENT MANAGEMENT: The US manufacturer of aripiprazole states that the dose of immediate release oral or injectable aripiprazole should be reduced to one-half of its normal dose when strong CYP3A4 inhibitors are coadministered, unless aripiprazole is being administered as adjunctive therapy for Major Depressive Disorder. If the patient is also receiving a strong CYP2D6 inhibitor or is a known CYP2D6 poor metabolizer, the dose of aripiprazole should be reduced to one-fourth its normal dose. When the inhibitors are discontinued, the dose of aripiprazole should be increased.(1) The US Department of Health and Human Services HIV guidelines state that patients on ritonavir- or cobicistat-boosted protease inhibitors should have their dose of aripiprazole decreased to one-fourth of the usual dose. Patients on unboosted atazanavir should have their aripiprazole decreased to one-half of the usual dose.(2) DISCUSSION: The coadministration of ketoconazole (200 mg daily for 14 days) with a single oral dose of aripiprazole (15 mg) resulted in increases in the area-under-curve (AUC) of aripiprazole and its active metabolite by 63% and 77%, respectively. In simulations, the combination of strong CYP2D6 and CYP3A4 inhibitors is predicted to increase aripiprazole Cmax and AUC by 4.5-fold. The concurrent use of strong CYP3A4 inhibitors in poor CYP2D6 metabolizers is predicted to increase aripiprazole Cmax and AUC by 3-fold.(1) CYP3A4 inhibitors linked to this monograph include: adagrasib, atazanavir, boceprevir, ceritinib, clarithromycin, cobicistat, darunavir, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, levoketoconazole, lonafarnib, lopinavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir, paritaprevir, posaconazole, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, and voriconazole.(3) |
APTIVUS, ATAZANAVIR SULFATE, CLARITHROMYCIN, CLARITHROMYCIN ER, DARUNAVIR, EVOTAZ, GENVOYA, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, KORLYM, KRAZATI, LANSOPRAZOL-AMOXICIL-CLARITHRO, LOPINAVIR-RITONAVIR, MIFEPREX, MIFEPRISTONE, NEFAZODONE HCL, NOXAFIL, OMECLAMOX-PAK, PAXLOVID, POSACONAZOLE, PREZCOBIX, PREZISTA, RECORLEV, REYATAZ, SPORANOX, STRIBILD, SYMTUZA, TOLSURA, TUKYSA, TYBOST, VFEND, VFEND IV, VIRACEPT, VOQUEZNA TRIPLE PAK, VORICONAZOLE, ZOKINVY, ZYDELIG, ZYKADIA |
| Aripiprazole Immediate Release/Slt Strong CYP2D6 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 aripiprazole.(1) CLINICAL EFFECTS: Concurrent administration of a strong CYP2D6 inhibitor with aripiprazole may result in elevated levels of and toxicity from aripiprazole.(1) PREDISPOSING FACTORS: The interaction is expected to be more severe in patients taking both a strong CYP3A4 inhibitor and a strong CYP2D6 inhibitor.(1) PATIENT MANAGEMENT: The US manufacturer of oral aripiprazole states that the dose of aripiprazole should be reduced to one-half of its normal dose when strong CYP2D6 inhibitors such as bupropion, fluoxetine, paroxetine and quinidine are coadministered, unless aripiprazole is being used as adjunctive therapy for Major Depressive Disorder. If the patient is also receiving a strong CYP3A4 inhibitor, the dose of aripiprazole should be reduced to one-fourth its normal dose. When the inhibitor(s) is(are) discontinued, the dose of aripiprazole should be increased.(1) DISCUSSION: The administration of quinidine (166 mg daily for 13 days, a strong inhibitor of CYP2D6) with a single dose of aripiprazole (10 mg) resulted in a 112% increase in the area-under-curve (AUC) of aripiprazole and a 35% decrease in the AUC of dehydro-aripiprazole, the active metabolite of aripiprazole.(1) Strong CYP2D6 inhibitors linked to this monograph are dacomitinib, fluoxetine, hydroquinidine, paroxetine, quinidine and terbinafine.(2-3) |
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 |
| 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; Levorphanol (IR)/Slt 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 codeine and levorphanol and antipsychotics, including phenothiazine derivatives, may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids such as codeine and levorphanol 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 codeine and levorphanol 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) |
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 |
| Aripiprazole Immediate Release/Bupropion SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong CYP2D6 inhibitors such as bupropion may inhibit the metabolism of aripiprazole.(1-2) Both agents are also known to lower the seizure threshold.(1,3-4) CLINICAL EFFECTS: Concurrent administration of a strong CYP2D6 inhibitor with aripiprazole may result in elevated levels of and toxicity from aripiprazole.(1) Concurrent use may also result in additive effects on the seizure threshold, increasing the risk of seizures.(3-4) PREDISPOSING FACTORS: The pharmacokinetic interaction is expected to be more severe in patients taking both a strong CYP3A4 inhibitor and a strong CYP2D6 inhibitor.(1) 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).(3-4) PATIENT MANAGEMENT: The concurrent use of bupropion and antipsychotics such as aripiprazole should be undertaken only with extreme caution and with low initial bupropion dosing, small gradual dosage increases of bupropion,(3-4) and reduced dosages of aripiprazole.(1) Single doses of bupropion should not exceed 150 mg.(3-4) The maximum daily dose of bupropion should not exceed 300 mg for smoking cessation(5) or 450 mg for depression.(3) The US manufacturer of oral aripiprazole states that the dose of aripiprazole should be reduced to one-half of its normal dose when strong CYP2D6 inhibitors, such as bupropion, are coadministered, unless aripiprazole is being used as adjunctive therapy for Major Depressive Disorder. If the patient is also receiving a strong CYP3A4 inhibitor, the dose of aripiprazole should be reduced to one-fourth its normal dose. When the inhibitor is discontinued, the dose of aripiprazole should be increased.(1) DISCUSSION: The administration of quinidine (166 mg daily for 13 days, a strong inhibitor of CYP2D6) with a single dose of aripiprazole (10 mg) resulted in a 112% increase in the area-under-curve (AUC) of aripiprazole and a 35% decrease in the AUC of dehydro-aripiprazole, the active metabolite of aripiprazole.(1) |
APLENZIN, AUVELITY, BUPROPION HCL, BUPROPION HCL SR, BUPROPION XL, CONTRAVE, FORFIVO XL, WELLBUTRIN SR, WELLBUTRIN XL |
| 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 |
The following contraindication information is available for ABILIFY (aripiprazole):
Drug contraindication overview.
Known hypersensitivity to aripiprazole; hypersensitivity reactions have ranged from pruritus/urticaria to anaphylaxis. (See Sensitivity Reactions under Cautions: Warnings/Precautions.)
Known hypersensitivity to aripiprazole; hypersensitivity reactions have ranged from pruritus/urticaria to anaphylaxis. (See Sensitivity Reactions under Cautions: Warnings/Precautions.)
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Parkinsonism |
There are 7 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic heart failure |
| CYp2d6 poor metabolizer |
| Metabolic syndrome x |
| Neuroleptic malignant syndrome |
| Senile dementia |
| Suicidal ideation |
| Tardive dyskinesia |
There are 16 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 |
| Agranulocytosis |
| Alzheimer's disease |
| Cerebrovascular disorder |
| Diabetes mellitus |
| Esophageal dysmotility |
| Hypotension |
| Leukopenia |
| Lower seizure threshold |
| Myocardial ischemia |
| Neutropenic disorder |
| Obesity |
| Orthostatic hypotension |
| Predisposition to aspiration |
| Seizure disorder |
| Weight gain |
The following adverse reaction information is available for ABILIFY (aripiprazole):
Adverse reaction overview.
Adverse effects occurring in 10% or more of adults receiving oral aripiprazole in clinical trials include nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, insomnia, and restlessness. Adverse effects occurring in 10% or more of pediatric patients receiving oral aripiprazole in clinical trials include somnolence, headache, vomiting, extrapyramidal disorder, fatigue, increased appetite, insomnia, nausea, nasopharyngitis, and increased weight. In clinical trials with aripiprazole tablets with sensor and other components of the digital ingestion tracking system (Abilify MyCite(R)), skin rash localized at the application site of the wearable sensor (patch) was reported in 12.4%
of patients. Other symptoms of skin irritation (e.g., pruritus, skin discoloration) have also been reported. Adverse effects occurring in 5% or more of adults receiving extended-release IM aripiprazole injection (Abilify Maintena(R)) for schizophrenia in clinical trials and at an incidence at least twice that for placebo include increased weight, akathisia, injection site pain, and sedation.
In patients receiving extended-release IM aripiprazole lauroxil injection (Aristada(R)) in clinical trials, akathisia was the only adverse effect that occurred in 5% of more of patients and at an incidence at least twice that for placebo. Other extrapyramidal adverse effects (e.g., parkinsonism, dystonia) and injection site reactions (e.g., pain) were reported in 5-7% and 4-5% of patients in the clinical trials, respectively.
Adverse effects occurring in 10% or more of adults receiving oral aripiprazole in clinical trials include nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, insomnia, and restlessness. Adverse effects occurring in 10% or more of pediatric patients receiving oral aripiprazole in clinical trials include somnolence, headache, vomiting, extrapyramidal disorder, fatigue, increased appetite, insomnia, nausea, nasopharyngitis, and increased weight. In clinical trials with aripiprazole tablets with sensor and other components of the digital ingestion tracking system (Abilify MyCite(R)), skin rash localized at the application site of the wearable sensor (patch) was reported in 12.4%
of patients. Other symptoms of skin irritation (e.g., pruritus, skin discoloration) have also been reported. Adverse effects occurring in 5% or more of adults receiving extended-release IM aripiprazole injection (Abilify Maintena(R)) for schizophrenia in clinical trials and at an incidence at least twice that for placebo include increased weight, akathisia, injection site pain, and sedation.
In patients receiving extended-release IM aripiprazole lauroxil injection (Aristada(R)) in clinical trials, akathisia was the only adverse effect that occurred in 5% of more of patients and at an incidence at least twice that for placebo. Other extrapyramidal adverse effects (e.g., parkinsonism, dystonia) and injection site reactions (e.g., pain) were reported in 5-7% and 4-5% of patients in the clinical trials, respectively.
There are 64 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Akathisia |
Acquired dystonia Extrapyramidal disease Fever Hyperglycemia Orthostatic hypotension Skin rash Tardive dyskinesia |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Accidental fall Acute myocardial infarction Agranulocytosis Anaphylaxis Angioedema Aspiration pneumonia Atrial flutter Atrioventricular block Biliary calculus Bradycardia Chest pain Cholecystitis Diabetes mellitus Diabetic ketoacidosis DRESS syndrome Dysglycemia Dysphagia Esophageal dysmotility Heat stroke Hepatic failure Hepatitis Hepatomegaly Homicidal ideation Hypertension Hypoglycemic disorder Hypokalemia Hyponatremia Hypoprolactinemia Hypotension Increased creatine kinase level Jaundice Laryngismus Leukopenia Myocardial ischemia Neuroleptic malignant syndrome Neutropenic disorder Oculogyric crisis Pancreatitis Parkinsonism Peripheral edema Pneumonia Priapism Rhabdomyolysis Seizure disorder Serotonin syndrome Sleep apnea Splenomegaly Steatosis of liver Stevens-johnson syndrome Suicidal ideation Tachycardia Thrombocytopenic disorder Upper respiratory infection Urinary retention Ventricular tachycardia |
There are 71 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Agitation Constipation Dizziness Dyspepsia Headache disorder Hypertriglyceridemia Increased appetite Insomnia Nausea Symptoms of anxiety Vomiting |
Acute abdominal pain Anorexia Arthralgia Cough Diarrhea Dysmenorrhea Fatigue Fecal incontinence General weakness Hyperlipidemia Hyperprolactinemia Injection site pain Injection site sequelae Myalgia Nasal congestion Nervousness Pain Pharyngitis Toothache Tremor Weight gain |
| Rare/Very Rare |
|---|
|
Amenorrhea Anticholinergic toxicity Ataxia Blurred vision Compulsive gambling Diplopia Drowsy Dyspnea Erectile dysfunction Eyelid edema Facial edema Gastroesophageal reflux disease Gynecomastia Hiccups Hirsutism Hyperhidrosis Hypokinesia Impulse control disorder Increased libido Lethargy Mastalgia Memory impairment Menstrual disorder Muscle rigidity Muscle weakness Myoclonus Nocturia Orgasm disorder Palpitations Photophobia Pruritus of skin Sedation Sialorrhea Skin photosensitivity Sleep walking disorder Urinary incontinence Urticaria Weight loss Xerostomia |
The following precautions are available for ABILIFY (aripiprazole):
Safety and efficacy of aripiprazole tablets with sensor have not been established in pediatric patients. Safety and efficacy of oral aripiprazole have not been established in pediatric patients with major depressive disorder. Safety and efficacy of extended-release IM formulations of aripiprazole and aripiprazole lauroxil have not been evaluated in pediatric patients younger than 18 years of age.
Safety and efficacy of oral aripiprazole for the acute management of schizophrenia in pediatric patients 13-17 years of age have been established in a placebo-controlled study of 6 weeks' duration. Although the efficacy of oral aripiprazole for maintenance treatment of schizophrenia in pediatric patients has not been systematically evaluated, the manufacturer states that such efficacy can be extrapolated from adult data in addition to comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. (See Schizophrenia under Uses: Psychotic Disorders.) Safety and efficacy of oral aripiprazole monotherapy for the acute management of bipolar mania in pediatric patients 10-17 years of age have been established in a placebo-controlled study of 4 weeks' duration.
The efficacy of oral aripiprazole as an adjunct to lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar disorder in pediatric patients has not been systematically evaluated. However, efficacy can be extrapolated from adult data in addition to pharmacokinetic comparisons of aripiprazole between adult and pediatric populations. Safety and efficacy of oral aripiprazole for the treatment of irritability associated with autistic disorder have been established in 2 placebo-controlled clinical trials of 8 weeks' duration in pediatric patients 6-17 years of age.
Efficacy of the drug as maintenance therapy for irritability associated with autistic disorder was not established in a longer-term, placebo-controlled relapse prevention trial in pediatric patients 6-17 years of age. Safety and efficacy of oral aripiprazole for the treatment of Tourette's syndrome have been established in one 8-week, placebo-controlled trial in pediatric patients 7-17 years of age and one 10-week, placebo-controlled trial in pediatric patients 6-18 years of age. Efficacy of the drug as maintenance therapy in pediatric patients with Tourette's syndrome has not been systematically evaluated.
(See Uses: Tourette's Syndrome.) The pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients 10-17 years of age are similar to those in adults after correcting for differences in body weight. Mean weight gain of 1.6 kg was reported in pediatric patients with schizophrenia or bipolar disorder receiving oral aripiprazole compared with a gain of 0.3
kg in those receiving placebo in 2 short-term studies. After 24 weeks of therapy, the mean change from baseline in body weight in the aripiprazole-treated patients was 5.8 kg compared with 1.4
kg in placebo recipients. Similar gains in weight were observed in short-term studies in pediatric patients with irritability associated with autistic disorder and Tourette's syndrome. FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and other antidepressants).
However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients younger than 19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials. These findings should be carefully considered when assessing potential benefits and risks of aripiprazole in a child or adolescent for any clinical use. (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Safety and efficacy of oral aripiprazole for the acute management of schizophrenia in pediatric patients 13-17 years of age have been established in a placebo-controlled study of 6 weeks' duration. Although the efficacy of oral aripiprazole for maintenance treatment of schizophrenia in pediatric patients has not been systematically evaluated, the manufacturer states that such efficacy can be extrapolated from adult data in addition to comparisons of aripiprazole pharmacokinetic parameters in adult and pediatric patients. (See Schizophrenia under Uses: Psychotic Disorders.) Safety and efficacy of oral aripiprazole monotherapy for the acute management of bipolar mania in pediatric patients 10-17 years of age have been established in a placebo-controlled study of 4 weeks' duration.
The efficacy of oral aripiprazole as an adjunct to lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar disorder in pediatric patients has not been systematically evaluated. However, efficacy can be extrapolated from adult data in addition to pharmacokinetic comparisons of aripiprazole between adult and pediatric populations. Safety and efficacy of oral aripiprazole for the treatment of irritability associated with autistic disorder have been established in 2 placebo-controlled clinical trials of 8 weeks' duration in pediatric patients 6-17 years of age.
Efficacy of the drug as maintenance therapy for irritability associated with autistic disorder was not established in a longer-term, placebo-controlled relapse prevention trial in pediatric patients 6-17 years of age. Safety and efficacy of oral aripiprazole for the treatment of Tourette's syndrome have been established in one 8-week, placebo-controlled trial in pediatric patients 7-17 years of age and one 10-week, placebo-controlled trial in pediatric patients 6-18 years of age. Efficacy of the drug as maintenance therapy in pediatric patients with Tourette's syndrome has not been systematically evaluated.
(See Uses: Tourette's Syndrome.) The pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients 10-17 years of age are similar to those in adults after correcting for differences in body weight. Mean weight gain of 1.6 kg was reported in pediatric patients with schizophrenia or bipolar disorder receiving oral aripiprazole compared with a gain of 0.3
kg in those receiving placebo in 2 short-term studies. After 24 weeks of therapy, the mean change from baseline in body weight in the aripiprazole-treated patients was 5.8 kg compared with 1.4
kg in placebo recipients. Similar gains in weight were observed in short-term studies in pediatric patients with irritability associated with autistic disorder and Tourette's syndrome. FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and other antidepressants).
However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients younger than 19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials. These findings should be carefully considered when assessing potential benefits and risks of aripiprazole in a child or adolescent for any clinical use. (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Neonates exposed to antipsychotic agents during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Symptoms reported to date have included agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, and feeding disorder. Neonates exhibiting such symptoms should be monitored.
The complications have varied in severity; some neonates recovered within hours to days without specific treatment, while others have 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.
National Pregnancy Registry for Atypical Antipsychotics: 866-961-2388 and http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregis try/atypicalantipsychotic/.
The complications have varied in severity; some neonates recovered within hours to days without specific treatment, while others have 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.
National Pregnancy Registry for Atypical Antipsychotics: 866-961-2388 and http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregis try/atypicalantipsychotic/.
Aripiprazole is distributed into milk in humans. However, data are insufficient to determine the amount present in human milk, the effects of the drug on breast-fed infants, or the effects on milk production. Because of the potential for serious adverse reactions to aripiprazole in nursing infants, the manufacturer of aripiprazole tablets states that a decision should be made whether to discontinue nursing or the drug, taking into consideration the importance of the drug to the woman. The manufacturers of extended-release IM formulations of aripiprazole and aripiprazole lauroxil state that the benefit of aripiprazole therapy to the woman as well as the benefits of breast-feeding to the infant should be weighed against the potential risk to the infant resulting from exposure to the drug or from the underlying maternal condition.
In clinical studies, approximately 8% of over 13,000 patients treated with oral aripiprazole were 65 years of age or older and approximately 6% were 75 years of age or older. Experience from placebo-controlled trials with oral aripiprazole in patients with schizophrenia, bipolar mania, or major depressive disorder who are 65 years of age and older is insufficient to determine whether they respond differently than younger adults. The manufacturer of oral and extended-release IM formulations of aripiprazole states that dosage adjustment is not necessary in geriatric patients on the basis of age alone.
The manufacturer of extended-release IM aripiprazole lauroxil states that the safety and efficacy of the drug have not been evaluated in patients older than 65 years of age and makes no specific dosage recommendations for geriatric patients. Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death. In addition, an increased incidence of adverse cerebrovascular events (cerebrovascular accidents and transient ischemic attacks), including fatalities, has been observed in geriatric patients with dementia-related psychosis treated with aripiprazole in placebo-controlled studies.
Aripiprazole is not approved for the treatment of dementia-related psychosis. (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Warnings/Precautions: Warnings, in Cautions and see also Adverse Cerebrovascular Events, including Stroke, in Geriatric Patients with Dementia-related Psychosis and see Dysphagia under Warnings/Precautions: Other Warnings and Precautions, in Cautions.) For additional information on the use of antipsychotic agents in the management of dementia-related psychosis, see Geriatric Considerations under Uses: Psychotic Disorders, in the Phenothiazines General Statement 28:16.08.24.
In pooled data analyses, a reduced risk of suicidality was observed in adults 65 years of age or older with antidepressant therapy compared with placebo. (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)
The manufacturer of extended-release IM aripiprazole lauroxil states that the safety and efficacy of the drug have not been evaluated in patients older than 65 years of age and makes no specific dosage recommendations for geriatric patients. Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death. In addition, an increased incidence of adverse cerebrovascular events (cerebrovascular accidents and transient ischemic attacks), including fatalities, has been observed in geriatric patients with dementia-related psychosis treated with aripiprazole in placebo-controlled studies.
Aripiprazole is not approved for the treatment of dementia-related psychosis. (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Warnings/Precautions: Warnings, in Cautions and see also Adverse Cerebrovascular Events, including Stroke, in Geriatric Patients with Dementia-related Psychosis and see Dysphagia under Warnings/Precautions: Other Warnings and Precautions, in Cautions.) For additional information on the use of antipsychotic agents in the management of dementia-related psychosis, see Geriatric Considerations under Uses: Psychotic Disorders, in the Phenothiazines General Statement 28:16.08.24.
In pooled data analyses, a reduced risk of suicidality was observed in adults 65 years of age or older with antidepressant therapy compared with placebo. (See Worsening of Depression and Suicidality Risk under Warnings/Precautions: Warnings, in Cautions.)
The following prioritized warning is available for ABILIFY (aripiprazole):
WARNING: If you are using aripiprazole in combination with other medication to treat depression, also carefully read the drug information for the other medication. 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: If you are using aripiprazole in combination with other medication to treat depression, also carefully read the drug information for the other medication. 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 ABILIFY (aripiprazole)'s list of indications:
| Bipolar disorder | |
| F31 | Bipolar disorder |
| F31.0 | Bipolar disorder, current episode hypomanic |
| F31.1 | Bipolar disorder, current episode manic without psychotic features |
| F31.10 | Bipolar disorder, current episode manic without psychotic features, unspecified |
| F31.11 | Bipolar disorder, current episode manic without psychotic features, mild |
| F31.12 | Bipolar disorder, current episode manic without psychotic features, moderate |
| F31.13 | Bipolar disorder, current episode manic without psychotic features, severe |
| F31.2 | Bipolar disorder, current episode manic severe with psychotic features |
| F31.3 | Bipolar disorder, current episode depressed, mild or moderate severity |
| F31.30 | Bipolar disorder, current episode depressed, mild or moderate severity, unspecified |
| F31.31 | Bipolar disorder, current episode depressed, mild |
| F31.32 | Bipolar disorder, current episode depressed, moderate |
| F31.4 | Bipolar disorder, current episode depressed, severe, without psychotic features |
| F31.5 | Bipolar disorder, current episode depressed, severe, with psychotic features |
| F31.6 | Bipolar disorder, current episode mixed |
| F31.60 | Bipolar disorder, current episode mixed, unspecified |
| F31.61 | Bipolar disorder, current episode mixed, mild |
| F31.62 | Bipolar disorder, current episode mixed, moderate |
| F31.63 | Bipolar disorder, current episode mixed, severe, without psychotic features |
| F31.64 | Bipolar disorder, current episode mixed, severe, with psychotic features |
| 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 |
| F31.8 | Other bipolar disorders |
| F31.81 | Bipolar II disorder |
| F31.89 | Other bipolar disorder |
| F31.9 | Bipolar disorder, unspecified |
| Gilles de la tourette syndrome | |
| F95.2 | Tourette's disorder |
| Infantile autism | |
| F84.0 | Autistic disorder |
| Major depressive disorder treatment adjunct | |
| F32.0 | Major depressive disorder, single episode, mild |
| F32.1 | Major depressive disorder, single episode, moderate |
| F32.2 | Major depressive disorder, single episode, severe without psychotic features |
| F32.3 | Major depressive disorder, single episode, severe with psychotic features |
| F32.9 | Major depressive disorder, single episode, unspecified |
| F33 | Major depressive disorder, recurrent |
| F33.0 | Major depressive disorder, recurrent, mild |
| F33.1 | Major depressive disorder, recurrent, moderate |
| F33.2 | Major depressive disorder, recurrent severe without psychotic features |
| F33.3 | Major depressive disorder, recurrent, severe with psychotic symptoms |
| F33.8 | Other recurrent depressive disorders |
| F33.9 | Major depressive disorder, recurrent, unspecified |
| 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