aripiprazole (Rx)

Brand and Other Names:Abilify, Abilify Maintena, more...Aristada
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 2mg
  • 5mg
  • 10mg
  • 15mg
  • 20mg
  • 30mg

oral disintegrating tablet

  • 10mg
  • 15mg

oral solution

  • 1mg/mL

extended-release injectable IM suspension (Abilify Maintena)

  • 300mg/vial or prefilled dual chamber syringe
  • 400mg/vial or prefilled dual chamber syringe

extended-release injectable IM suspension (aripiprazole lauroxil [Aristada])

  • 441mg/prefilled syringe (300 mg of aripiprazole)
  • 662mg/prefilled syringe (450 mg of aripiprazole)
  • 882mg/prefilled syringe (600 mg of aripiprazole)
  • 1064mg/prefilled syringe (724 mg of aripiprazole)
more...

Schizophrenia

PO

  • 10-15 mg/day PO initially; may increase after 2 weeks at each dose strength; not to exceed 30 mg/day PO when administered as tablet formulation; efficacy not significantly greater above 15 mg/day

Abilify Maintena

  • Patients who have never taken aripiprazole
    • 400 mg IM once monthly initially
    • Establish tolerability with aripiprazole PO prior to initiating treatment with Abilify Maintena; may take up to ~ 2 weeks to fully assess tolerability
    • Continue aripiprazole PO (10-20 mg/day) or other antipsychotics PO in patients with known aripiprazole tolerance for 14 consecutive days after initial injection
  • Patients stabilized or aripiprazole tolerant
    • 400 mg IM once monthly
    • Administer monthly dose no sooner than 26 days after previous injection (also see Dosage Modifications)
    • Consider dose reduction to 300 mg/month if adverse reaction occurs
  • See Administration

Aristada

  • Establish tolerability with PO aripiprazole before initiating Aristada; may take up to 2 weeks to fully assess tolerability
  • Base initial Aristada dose on current aripiprazole PO dose; coadminister aripiprazole PO for 21 consecutive days
  • 10 mg/day PO: 441 mg IM once monthly
  • 15 mg/day PO: 662 mg IM once monthly or 882 mg IM q6wk or 1064 mg IM q2mo
  • ≥20 mg/day PO: 882 mg IM once monthly
  • Adjust dose and dosing interval as needed; take into consideration the pharmacokinetics and prolonged-release characteristics of Aristada In the event of early dosing, Aristada should not be given earlier than 14 days after the previous injection
  • See Administration

Bipolar Mania

PO

  • Indicated for acute and maintenance treatment of manic or mixed episodes associated with bipolar I disorder, either as monotherapy or as adjunct to lithium or valproate
  • Monotherapy: 15 mg/day PO initially; may be increased gradually; not to exceed 30 mg/day
  • Adjunct to lithium or valproate: 10-15 mg/day PO initially; recommended daily dose is 15 mg/day; may be gradually increased; not to exceed 30 mg/day
  • Continue stabilization dose for up to 6 weeks; treatment >6 weeks not studied

Abilify Maintena

  • Patients who have never taken aripiprazole
    • 400 mg IM once monthly initially
    • Administer only by deep IM injection into deltoid or gluteal muscle by healthcare professional
    • Establish tolerability with aripiprazole PO prior to initiating treatment with Abilify Maintena; may take up to ~ 2 weeks to fully assess tolerability
    • Continue aripiprazole PO (10-20 mg/day) or other PO antipsychotics in patients with known aripiprazole tolerance for 14 consecutive days after initial injection
  • Patients stabilized or aripiprazole tolerant
    • 400 mg IM once monthly
    • Administer monthly dose no sooner than 26 days after previous injection (also see Dosage Modifications)
    • Consider dose reduction to 300 mg/month if adverse reaction occurs

Major Depressive Disorder

2-5 mg/day PO initially; increased weekly PRN by ≤5 mg/day to dose range of 2-15 mg/day

Used adjunctively with other antidepressants

Dosage Modifications (Oral)

Coadministration with potent CYP2D6 or CYP3A4 inhibitors: Decrease dose by 50%

Coadministration with potent CYP2D6 inhibitor PLUS a potent CYP3A4 inhibitor: Decrease dose to 25% of the usual dose (ie, decrease dose by 75%)

Coadministration with any CYP2D6 inhibitor PLUS any CYP3A4 inhibitor: Decrease dose to 25% of the usual dose (ie, decrease dose by 75%) initially, and then adjust to a favorable clinical response

Poor CYP2D6 metabolizers: Decrease dose by 50% initially, and then adjust to a favorable clinical response

Poor CYP3A4 metabolizers: Decrease dose to 25% of the usual dose (ie, decrease dose by 75%) initially, and then adjust to a favorable clinical response

Coadministration with potent CYP3A4 inducer: The usual dose should be doubled

Dosage Modifications (Abilify Maintena)

CYP2D6 poor metabolizers: 300 mg IM

CYP2D6 poor metabolizers taking concomitant CYP3A4 inhibitor: 200 mg IM

Patients taking 400 mg IM

  • Strong CYP2D6 OR CYP3A4 inhibitors: 300 mg IM
  • CYP2D6 AND CYP 3A4 inhibitors: 200 mg IM
  • CYP3A4 inducers: Avoid use

Patients taking 300 mg IM

  • Strong CYP2D6 OR CYP3A4 inhibitors: 200 mg IM
  • CYP2D6 AND CYP 3A4 inhibitors: 160 mg IM
  • CYP3A4 inducers: Avoid use

Missed doses

  • 2nd or 3rd dose missed (>4 wk but <5 wk since last injection): Administer injection as soon as possible
  • 2nd or 3rd dose missed (>5 wk since last injection): Restart concomitant oral aripiprazole for 14 days with next administered injection
  • 4th or subsequent doses missed (>4 wk but <6 wk since last injection): Administer injection as soon as possible
  • 4th or subsequent doses missed (>6 wk since last injection): Restart concomitant oral aripiprazole for 14 days with next administered injection

Dosage Modifications (Aristada)

No dosage changes if CYP450 modulators are added for <2 wk

Strong CYP3A4 inhibitor for >2 wk

  • Reduce the dose to the next lower strength No dosage adjustment necessary in patients taking 441 mg, if tolerated
  • Poor CYP2D6 metabolizers: Reduce dose to 441 mg from 662 mg, 882 mg, or 1064 mg; no dosage adjustment necessary in patients taking 441 mg, if tolerated

Strong CYP2D6 inhibitor for >2 wk

  • Reduce the dose to the next lower strength
  • No dosage adjustment necessary in patients taking 441 mg, if tolerated
  • Poor CYP2D6 metabolizers: No dose adjustment required

Both strong CYP3A4 & CYP2D6 inhibitors for >2 wk

  • Avoid use for patients taking 662 mg, 882 mg, or 1064 mg
  • No dosage adjustment necessary in patients taking 441 mg, if tolerated

CYP3A4 inducers for >2 wk

  • No dose adjustment for 662 mg, 882 mg, or 1064 mg
  • Increase the 441 mg dose to 662 mg

Missed doses

  • When a dose is missed, administer the next injection as soon as possible, unless the time has exceed 6-8 wk
  • Supplemental PO doses should be the same as when the patient initiated Aristada
  • See the following for recommendations for missed doses based on last injection dose
  • Monthly 441 mg
    • ≤6 wk: No PO supplementation required
    • >6 wk and ≤7 wk: Supplement with 7 days of PO aripiprazole
    • >7 wk: Supplement with 21 days of PO aripiprazole
  • Monthly 662 mg, monthly 882 mg, or 882 mg q6wk
    • ≤8 wk: No PO supplementation required
    • >8 wk and ≤12 wk: Supplement with 7 days of PO aripiprazole
    • >12 wk: Supplement with 21 days of PO aripiprazole
  • 1064 mg q2mo
    • ≤10 wk: No PO supplementation required
    • >10 wk and ≤12 wk: Supplement with 7 days of PO aripiprazole
    • >12 wk: Supplement with 21 days of PO aripiprazole

Dosing Considerations

Dosing for oral disintegrating tablets is the same as for oral tablets

Dosage Forms & Strengths

tablet

  • 2mg
  • 5mg
  • 10mg
  • 15mg
  • 20mg
  • 30mg

tablet, orally disintegrating

  • 10mg
  • 15mg

oral solution

  • 1mg/mL
more...

Schizophrenia

13-17 years: 2 mg/day PO initially; increase to 5 mg/day after 2 days; may further increase to recommended dose of 10 mg/day after additional 2 days; subsequent doses may increase by 5 mg/day; maintenance: 10-30 mg/day

Bipolar Mania

Indicated for acute manic or mixed episodes, either as monotherapy or as adjunct to lithium or valproate

10-17 years: 2 mg/day PO initially; increased to 5 mg/day after 2 days; may further increase to recommended dosage of 10 mg/day after additional 2 days; subsequent doses may increase by 5 mg/day; maintenance: 10-30 mg/day

Autism

Indicated for irritability associated with autistic disorder

<6 years: Safety and efficacy not established

6-17 years: 2 mg/day PO initially; increase gradually at ≥1 week intervals to target dosage of 5 mg/day; may gradually be further increase PRN to 10 mg/day or higher; not to exceed 15 mg/day

Tourette Disorder

Indicated for treatment of Tourette disorder

<6 years: Safety and efficacy not established

6-18 years (<50 kg)

  • Initiate at 2 mg/day PO with a target dose of 5 mg/day after 2 days
  • The dose can be increased to 10 mg/day in patients who do not achieve optimal control of tics
  • Dosage adjustments should occur gradually at intervals of no less than 1 week

6-18 years (≥50 kg)

  • Initiate at 2 mg/day PO for 2 days, and then increase to 5 mg/day for 5 days, with a target dose of 10 mg/day on day 8
  • The dose can be increased up to 20 mg/day for patients who do not achieve optimal control of tics
  • Dosage adjustments should occur gradually in increments of 5 mg/day at intervals of no less than 1 week

Dosage Modifications (Oral)

Coadministration with potent CYP2D6 or CYP3A4 inhibitors: Decrease dose by 50%

Coadministration with potent CYP2D6 inhibitor PLUS a potent CYP3A4 inhibitor: Decrease dose to 25% of the usual dose (ie, decrease dose by 75%)

Coadministration with any CYP2D6 inhibitor PLUS any CYP3A4 inhibitor: Decrease dose to 25% of the usual dose (ie, decrease dose by 75%) initially, and then adjust to a favorable clinical response

Poor CYP2D6 metabolizers: Decrease dose by 50% initially, and then adjust to a favorable clinical response

Poor CYP3A4 metabolizers: Decrease dose to 25% of the usual dose (ie, decrease dose by 75%) initially, and then adjust to a favorable clinical response

Coadministration with potent CYP3A4 inducer: The usual dose should be doubled

Dosing Considerations

Dosing for oral disintegrating tablets is the same as for oral tablets

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Interactions

Interaction Checker

and aripiprazole

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    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            >10%

            Weight gain (8-30%)

            Headache (27%)

            Agitation (19%)

            Insomnia (18%)

            Anxiety (17%)

            Nausea and vomiting (11-15%)

            Akathisia (10-13%)

            Lightheadedness (11%)

            Constipation (10-11%)

            1-10%

            Dizziness (10%)

            Dyspepsia (9%)  

            Somnolence (5-8%)

            Fatigue (6%) 

            Restlessness (6%)

            Tremor (6%)

            Dry mouth/xerostomia (5%) 

            Extrapyramidal disorder (5%) 

            Orthostatic hypotension (1-5%)

            Musculoskeletal stiffness (4%)

            Abdominal discomfort (3%) 

            Blurred vision (3%) 

            Cough (3%) 

            Pain (3%)

            Myalgia (2%) 

            Rash  

            Rhinitis  

            <1%

            Altered mental status

            Autonomic instability

            Dysphagia

            Hyperpyrexia

            Muscle rigidity

            Neuroleptic malignant syndrome (NMS)

            Seizure

            Tardive dyskinesia

            Postmarketing Reports

            Pathological gambling

            Hiccups

            Falls

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            Warnings

            Black Box Warnings

            Not approved for dementia-related psychosis; patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk of death, as shown in short-term controlled trials; deaths reported in trials appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature

            Antidepressants increased risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses, as shown in short-term studies; monitor for worsening and emergence of suicidal thoughts and behaviors

            Contraindications

            Documented hypersensitivity for aripiprazole

            Cautions

            Risk of extrapyramidal symptoms (EPS) (eg, pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia; monitor

            Tardive dyskinesia may occur; may consider discontinuation of therapy if clinically indicated

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

            May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy

            Use caution in patients with known cardiovascular disease, cerebrovascular disease, or predisposition to hypotension; may increase incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities)

            Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope

            Use caution in patients with Parkinson disease; may aggravate motor disturbances

            May increase risk of suicidal tendencies in children and adolescents

            FDA warning regarding off-label use for dementia in elderly

            Patients may act on dangerous impulses

            Monitor for orthostatic hypertension

            May cause seizures or convulsions; use cautiously in patients with history of seizures or with conditions that lower the seizure threshold

            May cause CNS depression, which may impair physical or mental abilities; use caution when operating heavy machinery

            Use caution in patients at risk of pneumonia; antipsychotic therapy has been associated with esophageal dysmotility and aspiration

            Impairment of core body temperature regulation possible; use caution in dehydration, heat exposure, strenuous exercise, and concomitant medication possessing anticholinergic effects

            Leukopenia, neutropenia, and agranulocytosis

            • Leukopenia/neutropenia and agranulocytosis reported; possible risk factors for leukopenia/neutropenia include preexisting low white blood cell (WBC) count and history of drug-induced leukopenia/neutropenia
            • If patient has history of clinically significant low WBC count or drug-induced leukopenia/neutropenia, monitor complete blood count (CBC) frequently during first few months of therapy; discontinue drug at first sign of clinically significant WBC decline <1000/mcL in absence of other causative factors, and continue monitoring WBC count until recovery

            Metabolic changes

            • Atypical antipsychotics have been associated with metabolic changes that may increase cardiovascular or cerebrovascular risk, including dyslipidemia and body weight gain
            • Increased risk of hyperglycemia and diabetes; in some cases, hyperglycemia concomitant with use of atypical antipsychotics has been associated with ketoacidosis, hyperosmolar coma, or death; monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness; monitor glucose regularly in patients with and at risk for diabetes
            • Significant weight gain reported with therapy; monitor waist circumference and BMI
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            Pregnancy & Lactation

            Pregnancy

            There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ARISTADA during pregnancy; For more information, contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/

            Neonates exposed to antipsychotic drugs during third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery; limited published data on aripiprazole use in pregnant women are not sufficient to inform any drug-associated risks for birth defects or miscarriage; no teratogenicity observed in animal reproductive studies with intramuscular administration of drug

            Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder reported in neonates exposed to antipsychotic drugs during the third trimester of pregnancy; symptoms have varied in severity; monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately; some neonates recover within hours or days without specific treatment; others required prolonged hospitalization

            Lactation

            Aripiprazole is present in human breast milk; however, there are insufficient data to assess amount in human milk, effects on breastfed infant, or effects on milk production; development and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from treatment or from underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Atypical antipsychotic; partial agonist at dopamine D2 and serotonin type 1 (5-HT1A) receptors; antagonist at serotonin type 2 (5-HT2A) receptor; also has alpha-blocking activity

            Absorption

            Bioavailability: 87% (tablet); 100% (IM)

            Peak plasma time: 1-3 hr (IR); 5-7 hr (ER); 3-5 hr (tablet)

            Distribution

            Protein bound: 99%

            Vd: 404 L (4.9 L/kg)

            Metabolism

            Metabolized by CYP2D6 and CYP3A4

            Metabolites: Dehydroaripiprazole (40%)

            Elimination

            Half-life: 75 hr (parent drug); 94 hr (metabolite); 30-47 days (IM); 146 hr (poor metabolizers)

            Excretion: Feces (55%), urine (25%)

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            Administration

            IM Preparation (Abilify Maintena)

            Do no substitute IM long-acting depot suspension formulations

            Vial

            • Reconstitute lyophilized power with sterile water for injection (SWI); discard any unused portion of diluent
            • 400 mg/vial: 1.9 mL SWI
            • 300 mg/vial: 1.5 mL SWI
            • Final concentration for either vial is 200 mg/mL following reconstitution
            • Slowly inject SWI into vial; shake the vial vigorously for 30 seconds until the reconstituted suspension appears uniform, homogeneous suspension that is opaque and milky-white.
            • Do not store reconstituted suspension in syringe Refer to manufacturer’s labeling for full preparation technique
            • Inject full syringe contents immediately following reconstitution
            • Immediate use is recommended; maintain vial at room temperature if dose is not immediately given; shake for 60 seconds to resuspend particles prior to injection; discard unused portion

            Prefilled syringe

            • Reconstitute at room temperature
            • Rotate the syringe plunger rod to release diluent
            • Shake vigorously for 20 seconds or until the suspension is uniform; the resulting suspension will be milky white and opaque (refer to manufacturer’s labeling for full preparation technique)
            • Inject full syringe contents immediately following reconstitution

            For both formulations, select appropriate hypodermic needle after completing IM preparation

            Needle for gluteal injection

            • Nonobese patient: 22-ga, 1.5-in
            • Obese patient: 21-ga, 2-in

            Needle for deltoid injection

            • Nonobese patient: 23-ga, 1-in
            • Obese patient: 22-ga, 1.5-in

            IM Preparation (Aristada)

            Tap the syringe on your palm at least 10 times to dislodge any material which may have settled, and then shake the syringe vigorously for a minimum of 30 seconds to ensure a uniform suspension; if the syringe is not used within 15 minutes, shake again for 30 seconds

            Injection site and associated needle length

            • 441 mg dose (deltoid): 21-ga, 1-in or 20-ga, 1.5-in
            • 441 mg, 662 mg, 882 mg, or 1064 mg doses (gluteal): 20-ga, 1.5-in or 20-ga 2-in

            Attach appropriate needle with a clockwise twisting motion; do not overtighten (could lead to needle hub cracking)

            Prime syringe to remove air by bringing the syringe into upright position and tap the syringe to bring air to the top; remove air by depressing the plunger rod; a few drops of suspension will be released

            Administer the entire content IM; inject in a rapid and continuous manner in <10 seconds

            Cover the needle by pressing the safety device, then dispose the needle, and used and unused items in proper waste container

            IM Administration

            Must be administered by a healthcare professional

            For IM use only; do not administer IV or SC

            Abilfy Maintena

            • Slowly inject dosage volume as a single IM injection into the deltoid or gluteal muscle
            • Do not massage the injection site

            Aristada

            • Administer the entire syringe content IM; inject in a rapid and continuous manner in <10 seconds
            • 441 mg once monthly: Administer in deltoid or gluteal muscle
            • 662 mg monthly, 882 mg monthly or q6wk: Administer in gluteal muscle
            • 1064 mg q2mo: Administer in gluteal muscle

            Storage

            PO solution and tablets: Store 77°F (25°C), excursions permitted between 59-86°F (15- 30°C) Use oral solution within 6 months after opening

            Abilify Maintena (prefilled dual chamber syringe): Store below 86°F (30°C) Do not freeze Protect the syringe from light by storing in the original package until time of use

            Abilify Maintena (vial): Store at room temperature 77°F (25°C), excursions permitted between 59-86°F (15- 30°C)

            Aristada: Store at room temperature 77°F (25°C), excursions permitted between 59-86°F (15- 30°C )

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            Formulary

            FormularyPatient Discounts

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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