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Drug overview for ABILIFY ASIMTUFII (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 commercially available in the US as aripiprazole and aripiprazole lauroxil.
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 commercially available in the US as aripiprazole and aripiprazole lauroxil.
DRUG IMAGES
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The following indications for ABILIFY ASIMTUFII (aripiprazole) have been approved by the FDA:
Indications:
Bipolar disorder in remission
Schizophrenia
Professional Synonyms:
Dementia praecox
Parergasia
Indications:
Bipolar disorder in remission
Schizophrenia
Professional Synonyms:
Dementia praecox
Parergasia
The following dosing information is available for ABILIFY ASIMTUFII (aripiprazole):
Aripiprazole oral solution may be given at the same dose on a mg-per-mg basis as the tablet strengths of the medication 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.
Of the available oral dosage forms of aripiprazole, aripiprazole oral film (Opipza(R)) is not indicated for use in pediatric or adult patients with manic and mixed episodes associated with bipolar I disorder.
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 manufacturers state 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.
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.
The manufacturers state that the need for continued therapy with the drug should be reassessed periodically.
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.
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 Asimtufii(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 Asimtufii(R)) is 960 mg administered by IM injection every 2 months (56 days following the previous injection). In patients experiencing adverse effects, a reduction in dosage to 720 mg every 2 months may be considered. The manufacturer states that dosages of Abilify Asimtufii(R) may be administered as early as 2 weeks before or 2 weeks following the scheduled 2-month dosage.
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.
When switching from once monthly Abilify Maintena(R) injections to extended-release aripiprazole injection (Abilify Asimtufii(R)) administer the first IM injection of Abilify Asimtufil(R) in place of the next scheduled injection of Abilify Maintena(R).
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. Extended-release aripiprazole lauroxil injection (Aristada(R)) may be initiated using 1 of 2 methods. The first method requires administration of one 30 mg dose of oral aripiprazole with a single 675 mg IM injection of aripiprazole lauroxil injection (Aristada Initio(R)) in conjunction with the first Aristada(R) injection.
The first Aristada(R) injection may be given within 10 days (as early as the same day) of the first Aristada Initio(R) injection, but IM injections must be administered into different muscles. The second method requires oral administration of aripiprazole with the first IM injection of Aristada(R) 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.
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 dose 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 (see Table 1 under Dosage and Administration).
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.
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.
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 Asimtufii(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 Asimtufii(R)) is 960 mg administered by IM injection every 2 months (56 days following the previous injection). In patients experiencing adverse effects, a reduction in dosage to 720 mg every 2 months may be considered. The manufacturer states that dosages of Abilify Asimtufii(R) may be administered as early as 2 weeks before or 2 weeks following the scheduled 2-month dosage.
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.
When switching from once monthly Abilify Maintena(R) injections to extended-release aripiprazole injection (Abilify Asimtufii(R)) administer the first IM injection of Abilify Asimtufil(R) in place of the next scheduled injection of Abilify Maintena(R).
For adjunctive management of major depressive disorder in adults already receiving an antidepressant, the manufacturer recommends an initial aripiprazole dosage of 2-5 mg orally once daily for acute treatment. Subsequent dosage adjustments of up to 5 mg daily should occur gradually at intervals of at least 1 week; the recommended dosage range is 2-15 mg once daily. The maximum recommended dosage is 15 mg daily.
Efficacy of the drug was established within a dosage range of 2-15 mg daily in clinical studies; mean maintenance dosage in these studies was approximately 11 mg daily.
The manufacturer states that if aripiprazole is used for maintenance therapy, the need for continued therapy with the drug should be reassessed periodically.
Potent CYP3A4 or CYP2D6 inhibitors: In patients receiving concomitant therapy with potent cytochrome P-450 (CYP) 3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole) or potent CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine), dosage of oral aripiprazole should be reduced to 50% of the usual dosage, except when oral aripiprazole is used in the adjunctive treatment of major depressive disorder. Dosage adjustment is not necessary when oral aripiprazole is used as adjunctive treatment of major depressive disorder.
In patients receiving concomitant therapy with potent CYP3A4 or CYP2D6 inhibitors for >14 days, dosage of extended-release aripiprazole injection (Abilify Maintena(R)) should be reduced from 400 mg to 300 mg every month, or from 300 mg to 200 mg every month. In such patients, dosage of extended-release aripiprazole lauroxil injection (Aristada(R))should be reduced to the next available lower strength; in patients tolerating the 441-mg dosage, dosage reduction is not necessary. A dosage of 882 mg every 6 weeks or 1064 mg every 2 months should be reduced to 441 mg every 4 weeks.
Dosage of extended-release aripiprazole injection (Abilify Asimtufii(R)) should be reduced from 960 mg every 2 months to 720 mg every 2 months. If the potent CYP3A4 or 2D6 inhibitor is used for <14 days, dosage adjustment of extended-release aripiprazole (Abilify Maintena(R), Abilify Asimtufii(R)) or aripiprazole lauroxil injection is not necessary.
Potent CYP3A4 and CYP2D6 inhibitors: In patients receiving concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors, oral aripiprazole dosage should be reduced to 25% of the usual dosage, except when aripiprazole is used in the adjunctive treatment of major depressive disorder. Dosage adjustment is not necessary when oral aripiprazole is used as adjunctive treatment of major depressive disorder.
In patients receiving concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors for >14 days, dosage of extended-release aripiprazole injection (Abilify Maintena(R)) should be reduced from 400 mg to 200 mg every month, or from 300 mg to 160 mg every month. In such patients tolerating the 441-mg dosage of extended-release aripiprazole lauroxil injection (Aristada(R)), dosage adjustment is not necessary; however, the manufacturer states that concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors for >2 weeks should be avoided in patients receiving 662-, 882-, or 1064-mg dosages of extended-release aripiprazole lauroxil injection. If such therapy is used for <14 days, dosage adjustment of extended-release aripiprazole (Abilify Maintena(R), Abilify Asimtufii(R)) or aripiprazole lauroxil injection is not necessary.
Concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors for >2 weeks should be avoided in patients receiving Abilify Asimtufii(R).
Combination of potent, moderate, or weak CYP3A4 and CYP2D6 inhibitors: Dosage of oral aripiprazole should be reduced to 25% of the usual dosage in patients receiving aripiprazole concurrently with a combination of potent, moderate, or weak inhibitors of CYP3A4 and CYP2D6 (e.g., a potent CYP3A4 inhibitor and a moderate CYP2D6 inhibitor or a moderate CYP3A4 inhibitor and a moderate CYP2D6 inhibitor). The oral aripiprazole dosage may then be adjusted based on clinical response.
Aripiprazole dosages should be increased back to the original dosage when the CYP3A4 inhibitor and/or CYP2D6 inhibitor is discontinued.
Potent CYP3A4 inducers: In patients receiving potent CYP3A4 inducers (e.g., carbamazepine, rifampin), dosage of oral aripiprazole should be doubled over 1-2 weeks of concomitant therapy. When the CYP3A4 inducer is discontinued, the dosage should be reduced back to the original dosage over 1-2 weeks.
The manufacturer recommends avoiding use of potent CYP3A4 inducers for >14 days in patients receiving extended-release aripiprazole injection (Abilify Maintena(R) or Abilify Asimtufii(R)).
In patients receiving extended-release aripiprazole lauroxil injection (Aristada(R)), if a potent CYP3A4 inducer is used for >2 weeks, dosage of aripiprazole lauroxil should be increased from 441 mg to 662 mg every month; dosage adjustment is not necessary in patients receiving 662-, 882-, or 1064-mg dosages. If a potent CYP3A4 inducer is used for <2 weeks, dosage adjustment is not necessary.
Extended-release aripiprazole lauroxil injection (Aristada Initio(R)) is only available in a single strength (675 mg); therefore, dosage adjustments in patients receiving potent CYP3A4 inhibitors, potent CYP2D6 inhibitors, or potent CYP3A4 inducers are not possible. Use of this extended-release formulation of the drug should be avoided in such patients.
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.
Of the available oral dosage forms of aripiprazole, aripiprazole oral film (Opipza(R)) is not indicated for use in pediatric or adult patients with manic and mixed episodes associated with bipolar I disorder.
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 manufacturers state 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.
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.
The manufacturers state that the need for continued therapy with the drug should be reassessed periodically.
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.
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 Asimtufii(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 Asimtufii(R)) is 960 mg administered by IM injection every 2 months (56 days following the previous injection). In patients experiencing adverse effects, a reduction in dosage to 720 mg every 2 months may be considered. The manufacturer states that dosages of Abilify Asimtufii(R) may be administered as early as 2 weeks before or 2 weeks following the scheduled 2-month dosage.
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.
When switching from once monthly Abilify Maintena(R) injections to extended-release aripiprazole injection (Abilify Asimtufii(R)) administer the first IM injection of Abilify Asimtufil(R) in place of the next scheduled injection of Abilify Maintena(R).
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. Extended-release aripiprazole lauroxil injection (Aristada(R)) may be initiated using 1 of 2 methods. The first method requires administration of one 30 mg dose of oral aripiprazole with a single 675 mg IM injection of aripiprazole lauroxil injection (Aristada Initio(R)) in conjunction with the first Aristada(R) injection.
The first Aristada(R) injection may be given within 10 days (as early as the same day) of the first Aristada Initio(R) injection, but IM injections must be administered into different muscles. The second method requires oral administration of aripiprazole with the first IM injection of Aristada(R) 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.
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 dose 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 (see Table 1 under Dosage and Administration).
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.
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.
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 Asimtufii(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 Asimtufii(R)) is 960 mg administered by IM injection every 2 months (56 days following the previous injection). In patients experiencing adverse effects, a reduction in dosage to 720 mg every 2 months may be considered. The manufacturer states that dosages of Abilify Asimtufii(R) may be administered as early as 2 weeks before or 2 weeks following the scheduled 2-month dosage.
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.
When switching from once monthly Abilify Maintena(R) injections to extended-release aripiprazole injection (Abilify Asimtufii(R)) administer the first IM injection of Abilify Asimtufil(R) in place of the next scheduled injection of Abilify Maintena(R).
For adjunctive management of major depressive disorder in adults already receiving an antidepressant, the manufacturer recommends an initial aripiprazole dosage of 2-5 mg orally once daily for acute treatment. Subsequent dosage adjustments of up to 5 mg daily should occur gradually at intervals of at least 1 week; the recommended dosage range is 2-15 mg once daily. The maximum recommended dosage is 15 mg daily.
Efficacy of the drug was established within a dosage range of 2-15 mg daily in clinical studies; mean maintenance dosage in these studies was approximately 11 mg daily.
The manufacturer states that if aripiprazole is used for maintenance therapy, the need for continued therapy with the drug should be reassessed periodically.
Potent CYP3A4 or CYP2D6 inhibitors: In patients receiving concomitant therapy with potent cytochrome P-450 (CYP) 3A4 inhibitors (e.g., clarithromycin, itraconazole, ketoconazole) or potent CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine), dosage of oral aripiprazole should be reduced to 50% of the usual dosage, except when oral aripiprazole is used in the adjunctive treatment of major depressive disorder. Dosage adjustment is not necessary when oral aripiprazole is used as adjunctive treatment of major depressive disorder.
In patients receiving concomitant therapy with potent CYP3A4 or CYP2D6 inhibitors for >14 days, dosage of extended-release aripiprazole injection (Abilify Maintena(R)) should be reduced from 400 mg to 300 mg every month, or from 300 mg to 200 mg every month. In such patients, dosage of extended-release aripiprazole lauroxil injection (Aristada(R))should be reduced to the next available lower strength; in patients tolerating the 441-mg dosage, dosage reduction is not necessary. A dosage of 882 mg every 6 weeks or 1064 mg every 2 months should be reduced to 441 mg every 4 weeks.
Dosage of extended-release aripiprazole injection (Abilify Asimtufii(R)) should be reduced from 960 mg every 2 months to 720 mg every 2 months. If the potent CYP3A4 or 2D6 inhibitor is used for <14 days, dosage adjustment of extended-release aripiprazole (Abilify Maintena(R), Abilify Asimtufii(R)) or aripiprazole lauroxil injection is not necessary.
Potent CYP3A4 and CYP2D6 inhibitors: In patients receiving concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors, oral aripiprazole dosage should be reduced to 25% of the usual dosage, except when aripiprazole is used in the adjunctive treatment of major depressive disorder. Dosage adjustment is not necessary when oral aripiprazole is used as adjunctive treatment of major depressive disorder.
In patients receiving concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors for >14 days, dosage of extended-release aripiprazole injection (Abilify Maintena(R)) should be reduced from 400 mg to 200 mg every month, or from 300 mg to 160 mg every month. In such patients tolerating the 441-mg dosage of extended-release aripiprazole lauroxil injection (Aristada(R)), dosage adjustment is not necessary; however, the manufacturer states that concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors for >2 weeks should be avoided in patients receiving 662-, 882-, or 1064-mg dosages of extended-release aripiprazole lauroxil injection. If such therapy is used for <14 days, dosage adjustment of extended-release aripiprazole (Abilify Maintena(R), Abilify Asimtufii(R)) or aripiprazole lauroxil injection is not necessary.
Concomitant therapy with potent CYP3A4 inhibitors and potent CYP2D6 inhibitors for >2 weeks should be avoided in patients receiving Abilify Asimtufii(R).
Combination of potent, moderate, or weak CYP3A4 and CYP2D6 inhibitors: Dosage of oral aripiprazole should be reduced to 25% of the usual dosage in patients receiving aripiprazole concurrently with a combination of potent, moderate, or weak inhibitors of CYP3A4 and CYP2D6 (e.g., a potent CYP3A4 inhibitor and a moderate CYP2D6 inhibitor or a moderate CYP3A4 inhibitor and a moderate CYP2D6 inhibitor). The oral aripiprazole dosage may then be adjusted based on clinical response.
Aripiprazole dosages should be increased back to the original dosage when the CYP3A4 inhibitor and/or CYP2D6 inhibitor is discontinued.
Potent CYP3A4 inducers: In patients receiving potent CYP3A4 inducers (e.g., carbamazepine, rifampin), dosage of oral aripiprazole should be doubled over 1-2 weeks of concomitant therapy. When the CYP3A4 inducer is discontinued, the dosage should be reduced back to the original dosage over 1-2 weeks.
The manufacturer recommends avoiding use of potent CYP3A4 inducers for >14 days in patients receiving extended-release aripiprazole injection (Abilify Maintena(R) or Abilify Asimtufii(R)).
In patients receiving extended-release aripiprazole lauroxil injection (Aristada(R)), if a potent CYP3A4 inducer is used for >2 weeks, dosage of aripiprazole lauroxil should be increased from 441 mg to 662 mg every month; dosage adjustment is not necessary in patients receiving 662-, 882-, or 1064-mg dosages. If a potent CYP3A4 inducer is used for <2 weeks, dosage adjustment is not necessary.
Extended-release aripiprazole lauroxil injection (Aristada Initio(R)) is only available in a single strength (675 mg); therefore, dosage adjustments in patients receiving potent CYP3A4 inhibitors, potent CYP2D6 inhibitors, or potent CYP3A4 inducers are not possible. Use of this extended-release formulation of the drug should be avoided in such patients.
Aripiprazole is administered orally or by IM injection. Aripiprazole lauroxil is administered only by IM injection.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| ABILIFY ASIMTUFII 720 MG/2.4ML | Maintenance | Adults inject 720 mg by intramuscular route every 2 months |
| ABILIFY ASIMTUFII 960 MG/3.2ML | Maintenance | Adults inject 960 mg by intramuscular route every 2 months |
No generic dosing information available.
The following drug interaction information is available for ABILIFY ASIMTUFII (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) The US manufacturer of doxepin states if concurrent use of doxepin and strong CYP2D6 inhibitors such as mavorixafor is warranted, monitor doxepin plasma concentrations and reduce the doxepin dose based on doxepin plasma concentrations.(5) 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, atomoxetine, 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 |
| 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. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. Consider these risks 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 opioid reversal agents (e.g., naloxone, nalmefene) with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing an opioid reversal agent (e.g., naloxone, nalmefene) to patients prescribed medicines to treat OUD or opioid analgesics who are at increased risk of opioid overdose (such as those taking CNS depressants) and when a patient has household members/close contacts at risk for accidental overdose. Discuss the options for obtaining an opioid reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).(3) DISCUSSION: A nested case-control study looked at the relationship between antipsychotic use and risk of acute respiratory failure. Current use of antipsychotics was associated with a 2.33-fold increase in risk of respiratory failure compared to no use of antipsychotics. The risk was also significantly increased in patients with recent use of antipsychotics (within the past 15-30 days, OR = 1.79) and recent past use (within 31-90 days OR = 1.41). The risk increased with higher doses and longer duration of use.(4) Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
HYCODAN, HYDROCODONE-CHLORPHENIRAMNE ER, HYDROCODONE-HOMATROPINE MBR, HYDROMET, PROMETHAZINE-CODEINE, TUXARIN ER |
| Selected Long-Acting Aripiprazole Injections/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.(1,2) CLINICAL EFFECTS: Strong CYP3A4 inducers may result in decreased levels and effectiveness of aripiprazole.(1,2) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of the extended release injectable aripiprazole lauroxil, submicronized (Aristada Initio) recommends avoiding use of strong CYP3A4 inducers with Aristada Initio. Aristada Initio is only available in a single strength as a single-dose prefilled syringe.(1) For patients receiving aripiprazole extended-release injection (Abilify Maintena or Abilify Asimtuffi), dose adjustments are not recommended by the manufacturer if the duration of strong CYP3A4 inducer treatment is less than 14 days. Concurrent use of Abilify Maintena or Abilify Asimtuffi with strong CYP3A4 inducers for greater than 14 days should be avoided.(2-3) DISCUSSION: Drug interaction studies have not been conducted with Aristada Initio,(1) Abilify Maintena,(2) or Abilify Asimtuffi.(3) Aristada Initio has a long half-life (15-18 days).(1) Abilify Maintena has a half-life of 29.9 days and 46.5 days after multiple injections for every 4-week injection with the 300 mg and 400 mg dose, respectively.(2) 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) Strong CYP3A4 inducers linked to this monograph are: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, natisedine, phenytoin, primidone, rifampin, rifapentine and St. John's Wort.(4-5) |
ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BRAFTOVI, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EQUETRO, ERLEADA, FIORICET, 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, TIBSOVO, XTANDI |
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 |
|---|---|
| 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 ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.(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. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. Consider these risks 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 opioid reversal agents (e.g., naloxone, nalmefene) with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing an opioid reversal agent (e.g., naloxone, nalmefene) to patients prescribed medicines to treat OUD or opioid analgesics who are at increased risk of opioid overdose (such as those taking CNS depressants) and when a patient has household members/close contacts at risk for accidental overdose. Discuss the options for obtaining an opioid reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).(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, TAPENTADOL 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 ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.(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. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. Consider these risks 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 opioid reversal agents (e.g., naloxone, nalmefene) with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing an opioid reversal agent (e.g., naloxone, nalmefene) to patients prescribed medicines to treat OUD or opioid analgesics who are at increased risk of opioid overdose (such as those taking CNS depressants) and when a patient has household members/close contacts at risk for accidental overdose. Discuss the options for obtaining an opioid reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).(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) |
BELBUCA, BELLADONNA-OPIUM, 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, OPIUM TINCTURE, OXYCODONE HCL, OXYCODONE HYDROCHLORIDE, OXYCODONE-ACETAMINOPHEN, OXYMORPHONE HCL, PENTAZOCINE-NALOXONE HCL, PERCOCET, PRIMLEV, PROLATE, REMIFENTANIL HCL, ROXICODONE, ROXYBOND, SUFENTANIL CITRATE, TAPENTADOL HCL, 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. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. Consider these risks 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 opioid reversal agents (e.g., naloxone, nalmefene) with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing an opioid reversal agent (e.g., naloxone, nalmefene) to patients prescribed medicines to treat OUD or opioid analgesics who are at increased risk of opioid overdose (such as those taking CNS depressants) and when a patient has household members/close contacts at risk for accidental overdose. Discuss the options for obtaining an opioid reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).(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 ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.(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. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. Consider these risks 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 opioid reversal agents (e.g., naloxone, nalmefene) with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing an opioid reversal agent (e.g., naloxone, nalmefene) to patients prescribed medicines to treat OUD or opioid analgesics who are at increased risk of opioid overdose (such as those taking CNS depressants) and when a patient has household members/close contacts at risk for accidental overdose. Discuss the options for obtaining an opioid reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).(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 ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.(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. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. Consider these risks 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 opioid reversal agents (e.g., naloxone, nalmefene) with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing an opioid reversal agent (e.g., naloxone, nalmefene) to patients prescribed medicines to treat OUD or opioid analgesics who are at increased risk of opioid overdose (such as those taking CNS depressants) and when a patient has household members/close contacts at risk for accidental overdose. Discuss the options for obtaining an opioid reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).(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, HYDROCODONE BITARTRATE, LEVORPHANOL TARTRATE, TREZIX, XYVONA |
| 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 ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.(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. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. Consider these risks 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 opioid reversal agents (e.g., naloxone, nalmefene) with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing an opioid reversal agent (e.g., naloxone, nalmefene) to patients prescribed medicines to treat OUD or opioid analgesics who are at increased risk of opioid overdose (such as those taking CNS depressants) and when a patient has household members/close contacts at risk for accidental overdose. Discuss the options for obtaining an opioid reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).(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 ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.(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. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. Consider these risks 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 opioid reversal agents (e.g., naloxone, nalmefene) with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing an opioid reversal agent (e.g., naloxone, nalmefene) to patients prescribed medicines to treat OUD or opioid analgesics who are at increased risk of opioid overdose (such as those taking CNS depressants) and when a patient has household members/close contacts at risk for accidental overdose. Discuss the options for obtaining an opioid reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).(3) DISCUSSION: A nested case-control study looked at the relationship between antipsychotic use and risk of acute respiratory failure. Current use of antipsychotics was associated with a 2.33-fold increase in risk of respiratory failure compared to no use of antipsychotics. The risk was also significantly increased in patients with recent use of antipsychotics (within the past 15-30 days, OR = 1.79) and recent past use (within 31-90 days OR = 1.41). The risk increased with higher doses and longer duration of use.(4) Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
QDOLO, TRAMADOL HCL, TRAMADOL HCL-ACETAMINOPHEN |
| Apomorphine/Select Atypical Antipsychotics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Apomorphine is a dopamine agonist. Antipsychotic agents counteract this effect by blocking dopamine activity at CNS D2 receptors.(1) CLINICAL EFFECTS: The efficacy of either agent may be decreased, leading to exacerbation of the disease being treated, e.g. Parkinson disease or a psychotic disorder. PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body(DLB) disease are particularly susceptible to adverse effects of dopamine blockade by antipsychotics. PATIENT MANAGEMENT: Reassess the need for antipsychotic therapy. If psychosis or hallucinations are due to an antiparkinson agent, when possible consider reducing the dose or changing the antiparkinson agent before initiating antipsychotic therapy. In patients with PD and dementia, addition of a cholinesterase inhibitor (e.g. rivastigmine) may improve psychosis. If an antipsychotic is required, then an atypical antipsychotic should be used.(2,3) The US manufacturer of apomorphine states patients with major psychotic disorders treated with neuroleptics should be treated with dopamine agonists only if the potential benefits outweigh the risks.(1) DISCUSSION: An epidemiologic study evaluated 21,043 elderly patients with Parkinson disease to determine if recent initiation of a typical or atypical antipsychotic was associated with increased mortality. They found an adjusted odds ratio of 2.0 for death associated with atypical antipsychotics versus no antipsychotic. They found an adjusted odds ratio of 2.4 for death associated with typical versus atypical antipsychotics. The authors noted the increased mortality found with typical antipsychotics supports current treatment recommendations to use atypical antipsychotic agents in patients with Parkinson disease.(2,3) Two clozapine trials showed significant improvement in psychosis without worsening of motor symptoms. In contrast, two olanzapine trials were associated with unacceptable worsening of motor symptoms. Risperidone has also been associated with motor worsening in case reports. Quetiapine evaluations have been conflicting with several small studies showing improvement in psychotic symptoms while a more rigorous trial showed no improvement.(2) |
APOKYN, APOMORPHINE HCL, ONAPGO |
| Aripiprazole IM Every 2 Months (Abilify Asimtufii)/Strong CYP3A4 Inhibitors; 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) CLINICAL EFFECTS: Concurrent administration of a strong CYP3A4 inhibitor may result in elevated levels of and toxicity from aripiprazole.(1) 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) PATIENT MANAGEMENT: The US manufacturer of aripiprazole IM every 2 months injection (Abilify Asimtufii) makes the following recommendations for patients who receive a strong CYP3A4 inhibitor for greater than 14 days:(1) - if the aripiprazole dose is 960 mg every 2 months and a strong CYP3A4 inhibitor is started, reduce the aripiprazole dose to 720 mg once every 2 months. - if the patient is taking both a strong CYP3A4 inhibitor AND a strong CYP2D6 inhibitor, avoid use of Abilify Asimtufii. - if the patient is a poor CYP2D6 metabolizer and receives treatment with a strong CYP3A4 inhibitor, avoid use of Abilify Asimtufii. DISCUSSION: There have been no specific drug-drug interaction studies with aripiprazole long-acting injections. 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.(2) |
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, VFEND, VFEND IV, VIRACEPT, VOQUEZNA TRIPLE PAK, VORICONAZOLE, VORICONAZOLE (HPBCD), ZOKINVY, ZYDELIG, ZYKADIA |
| Aripiprazole IM Every 2 Months (Abilify Asimtufii)/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 aripiprazole IM every 2 months injection (Abilify Asimtufii) makes the following recommendations for patients who receive a strong CYP2D6 inhibitor for greater than 14 days:(1) - if the aripiprazole dose is 960 mg every 2 months and a strong CYP2D6 inhibitor is started, reduce the aripiprazole dose to 720 mg once every 2 months. - if the patient is taking both a strong CYP2D6 inhibitor AND a strong CYP3A4 inhibitor, avoid use of Abilify Asimtufii. DISCUSSION: There have been no specific drug-drug interaction studies with aripiprazole long-acting injections. 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. In simulations, the combination of strong CYP2D6 and CYP3A4 inhibitors is predicted to increase aripiprazole Cmax and AUC by 4.5-fold.(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 |
| Aripiprazole IM Every 2 Months (Abilify Asimtufii)/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. Both agents are also known to lower the seizure threshold.(1-3) CLINICAL EFFECTS: Concurrent administration of a strong CYP2D6 inhibitor with aripiprazole may result in elevated levels of and toxicity from aripiprazole. Concurrent use may also result in additive effects on the seizure threshold, increasing the risk of seizures.(1-3) 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).(2-3) 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,(2-3) and reduced dosages of aripiprazole.(1) Single doses of bupropion should not exceed 150 mg.(2-3) The maximum daily dose of bupropion should not exceed 300 mg for smoking cessation(3) or 450 mg for depression.(2) The US manufacturer of aripiprazole IM every 2 months injection (Abilify Asimtufii) makes the following recommendations for patients who receive a strong CYP2D6 inhibitor for greater than 14 days:(1) - if the aripiprazole dose is 960 mg every 2 months and a strong CYP2D6 inhibitor is started, reduce the aripiprazole dose to 720 mg once every 2 months. - if the patient is taking both a strong CYP2D6 inhibitor AND a strong CYP3A4 inhibitor, avoid use of Abilify Asimtufii. DISCUSSION: There have been no specific drug-drug interaction studies with aripiprazole long-acting injections. 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. In simulations, the combination of strong CYP2D6 and CYP3A4 inhibitors is predicted to increase aripiprazole Cmax and AUC by 4.5-fold.(1) |
APLENZIN, AUVELITY, BUPROPION HCL, BUPROPION HCL SR, BUPROPION XL, CONTRAVE, WELLBUTRIN SR, WELLBUTRIN XL |
The following contraindication information is available for ABILIFY ASIMTUFII (aripiprazole):
Drug contraindication overview.
*Known hypersensitivity to aripiprazole; hypersensitivity reactions have ranged from pruritus/urticaria to anaphylaxis.
*Known hypersensitivity to aripiprazole; hypersensitivity reactions have ranged from pruritus/urticaria to anaphylaxis.
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 ASIMTUFII (aripiprazole):
Adverse reaction overview.
In adults with schizophrenia receiving oral aripiprazole in clinical trials, akathisia was the only adverse effect that occurred in >=5% of patients and at an incidence at least twice that for placebo. Adverse effects occurring in >=5% of adolescents (13 to 17 years of age) with schizophrenia receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include extrapyramidal disorder, somnolence, and tremor. Adverse effects occurring in >=5% of adults with bipolar mania receiving oral aripiprazole as monotherapy in clinical trials and at an incidence at least twice that of placebo include akathisia, sedation, restlessness, tremor, and extrapyramidal disorder.
Adverse effects occurring in >=5% of adults with bipolar mania receiving oral aripiprazole as adjunctive therapy with lithium or valproate in clinical trials and at an incidence at least twice that of placebo include akathisia, insomnia, and extrapyramidal disorder. Adverse effects occurring in >=5% of pediatric patients 10 to 17 years of age with bipolar mania receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include somnolence, extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary hypersecretion, and dizziness. Adverse effects occurring in >=5% of adults with major depressive disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision.
Adverse effects occurring in >=5% of pediatric patients 6 to 17 years of age with autistic disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include sedation, fatigue, vomiting, somnolence, tremor, pyrexia, drooling, decreased appetite, salivary hypersecretion, extrapyramidal disorder, and lethargy. Adverse effects occurring in >=5% of pediatric patients 6 to 18 years of age with Tourette's Disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include sedation, somnolence, nausea, headache, nasopharyngitis, fatigue, and increased appetite. 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. Adverse effects occurring in >=5% of adults receiving extended-release IM aripiprazole injection 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 patients and at an incidence at least twice that for placebo.
In adults with schizophrenia receiving oral aripiprazole in clinical trials, akathisia was the only adverse effect that occurred in >=5% of patients and at an incidence at least twice that for placebo. Adverse effects occurring in >=5% of adolescents (13 to 17 years of age) with schizophrenia receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include extrapyramidal disorder, somnolence, and tremor. Adverse effects occurring in >=5% of adults with bipolar mania receiving oral aripiprazole as monotherapy in clinical trials and at an incidence at least twice that of placebo include akathisia, sedation, restlessness, tremor, and extrapyramidal disorder.
Adverse effects occurring in >=5% of adults with bipolar mania receiving oral aripiprazole as adjunctive therapy with lithium or valproate in clinical trials and at an incidence at least twice that of placebo include akathisia, insomnia, and extrapyramidal disorder. Adverse effects occurring in >=5% of pediatric patients 10 to 17 years of age with bipolar mania receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include somnolence, extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary hypersecretion, and dizziness. Adverse effects occurring in >=5% of adults with major depressive disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision.
Adverse effects occurring in >=5% of pediatric patients 6 to 17 years of age with autistic disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include sedation, fatigue, vomiting, somnolence, tremor, pyrexia, drooling, decreased appetite, salivary hypersecretion, extrapyramidal disorder, and lethargy. Adverse effects occurring in >=5% of pediatric patients 6 to 18 years of age with Tourette's Disorder receiving oral aripiprazole in clinical trials and at an incidence at least twice that of placebo include sedation, somnolence, nausea, headache, nasopharyngitis, fatigue, and increased appetite. 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. Adverse effects occurring in >=5% of adults receiving extended-release IM aripiprazole injection 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 patients and at an incidence at least twice that for placebo.
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 ASIMTUFII (aripiprazole):
Safety and efficacy of oral aripiprazole have not been established in pediatric patients with major depressive disorder. Safety and efficacy of oral aripiprazole have not been established in pediatric patients with agitation associated with schizophrenia or bipolar mania. Safety and efficacy of extended-release IM formulations of aripiprazole and aripiprazole lauroxil have not been evaluated in pediatric patients <18 years of age.
Safety and efficacy of aripiprazole tablets with sensor have not been established in pediatric patients. Safety and efficacy of oral aripiprazole for the acute management of schizophrenia in pediatric patients 13 to 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.
Safety and efficacy of oral aripiprazole monotherapy for the acute management of bipolar mania in pediatric patients 10 to 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 to 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 to 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 to 17 years of age and one 10-week, placebo-controlled trial in pediatric patients 6 to 18 years of age.
Efficacy of the drug as maintenance therapy in pediatric patients with Tourette's syndrome has not been systematically evaluated. The pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients 10 to 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.
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). 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.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Safety and efficacy of aripiprazole tablets with sensor have not been established in pediatric patients. Safety and efficacy of oral aripiprazole for the acute management of schizophrenia in pediatric patients 13 to 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.
Safety and efficacy of oral aripiprazole monotherapy for the acute management of bipolar mania in pediatric patients 10 to 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 to 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 to 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 to 17 years of age and one 10-week, placebo-controlled trial in pediatric patients 6 to 18 years of age.
Efficacy of the drug as maintenance therapy in pediatric patients with Tourette's syndrome has not been systematically evaluated. The pharmacokinetics of aripiprazole and dehydro-aripiprazole in pediatric patients 10 to 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.
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). 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.
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 and managed appropriately.
The complications have varied in severity; some neonates recovered within hours to days without specific treatment, while others have required prolonged hospitalization. There is a pregnancy registry that monitors pregnancy outcomes in females exposed to atypical antipsychotics during pregnancy. Clinicians are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 866-961-2388 and https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregi stry/atypicalantipsychotic/.
The complications have varied in severity; some neonates recovered within hours to days without specific treatment, while others have required prolonged hospitalization. There is a pregnancy registry that monitors pregnancy outcomes in females exposed to atypical antipsychotics during pregnancy. Clinicians are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 866-961-2388 and https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregi stry/atypicalantipsychotic/.
Limited data indicate that aripiprazole is present in human milk at a relative infant dose (RID) ranging from 0.7-8.3% of the maternal weight-adjusted dosage.
Poor weight gain in breast-fed infants exposed to aripiprazole and inadequate milk supply in lactating women have been reported. The manufacturers of aripiprazole state that the benefit of aripiprazole therapy to the mother 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.
Poor weight gain in breast-fed infants exposed to aripiprazole and inadequate milk supply in lactating women have been reported. The manufacturers of aripiprazole state that the benefit of aripiprazole therapy to the mother 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 and approximately 6% were >=75 years of age. Experience from placebo-controlled trials with oral aripiprazole in patients with schizophrenia, bipolar mania, or major depressive disorder who are >=65 years of age 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 >65 years of age and makes no specific dosage recommendations for geriatric patients. The manufacturer of extended-release IM aripiprazole (Abilify Asimtufii(R)) states that an insufficient number of patients >=65 years of age were included in clinical trials to assess differences in response compared to younger adults; however, dosage selection for elderly patients should be undertaken with caution and dosages should be initiated at the lower end of the dosage range. 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 TIAs), 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. In pooled data analyses, a reduced risk of suicidality was observed in adults >=65 years of age with antidepressant therapy compared with placebo.
The manufacturer of extended-release IM aripiprazole lauroxil states that the safety and efficacy of the drug have not been evaluated in patients >65 years of age and makes no specific dosage recommendations for geriatric patients. The manufacturer of extended-release IM aripiprazole (Abilify Asimtufii(R)) states that an insufficient number of patients >=65 years of age were included in clinical trials to assess differences in response compared to younger adults; however, dosage selection for elderly patients should be undertaken with caution and dosages should be initiated at the lower end of the dosage range. 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 TIAs), 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. In pooled data analyses, a reduced risk of suicidality was observed in adults >=65 years of age with antidepressant therapy compared with placebo.
The following prioritized warning is available for ABILIFY ASIMTUFII (aripiprazole):
WARNING: There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.
WARNING: There may be a slightly increased risk of serious, possibly fatal side effects (such as stroke, heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.
The following icd codes are available for ABILIFY ASIMTUFII (aripiprazole)'s list of indications:
| Bipolar disorder in remission | |
| F31.7 | Bipolar disorder, currently in remission |
| F31.70 | Bipolar disorder, currently in remission, most recent episode unspecified |
| F31.71 | Bipolar disorder, in partial remission, most recent episode hypomanic |
| F31.72 | Bipolar disorder, in full remission, most recent episode hypomanic |
| F31.73 | Bipolar disorder, in partial remission, most recent episode manic |
| F31.74 | Bipolar disorder, in full remission, most recent episode manic |
| F31.75 | Bipolar disorder, in partial remission, most recent episode depressed |
| F31.76 | Bipolar disorder, in full remission, most recent episode depressed |
| F31.77 | Bipolar disorder, in partial remission, most recent episode mixed |
| F31.78 | Bipolar disorder, in full remission, most recent episode mixed |
| Schizophrenia | |
| F20 | Schizophrenia |
| F20.0 | Paranoid schizophrenia |
| F20.1 | Disorganized schizophrenia |
| F20.2 | Catatonic schizophrenia |
| F20.3 | Undifferentiated schizophrenia |
| F20.5 | Residual schizophrenia |
| F20.8 | Other schizophrenia |
| F20.81 | Schizophreniform disorder |
| F20.89 | Other schizophrenia |
| F20.9 | Schizophrenia, unspecified |
Formulary Reference Tool