aripiprazole (Rx)

>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

Aripiprazole lauroxil

• Extrapyramidal symptoms (5-7%)
• Injection site reactions (4%)
• Pain at injection site (<2%)
• Increased weight (<2%)
• Increased creatinine phosphokinase (<2%)
• Akathisia (<2%)
• Headache (<2%)
• Insomnia (<2%)
• Restlessness (<2%)

<1%

Altered mental status

Autonomic instability

Dysphagia

Hyperpyrexia

Muscle rigidity

Neuroleptic malignant syndrome (NMS)

Seizure

Tardive dyskinesia

Aripiprazole lauroxil

• Cardiac – Angina pectoris, tachycardia, palpitations
• Gastrointestinal disorders – Constipation, dry mouth
• General disorders – Asthenia
• Musculoskeletal – Muscular weakness
• Nervous system disorders – Dizziness
• Psychiatric disorders – Anxiety, suicide

Postmarketing Reports

Pathological gambling

Hiccups

Falls

Aripiprazole lauroxil

• Occurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups and blood glucose fluctuation

Contraindications

Hypersensitivity to 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 (eg, 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 (see Black Box Warnings)

FDA warning regarding off-label use for dementia in elderly (see Black Box Warnings)

Patients may act on dangerous impulses (eg, gambling)

Monitor for orthostatic hypotension

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

Potential dosing and medication errors

• Aristada and Aristada Initio
• Medication errors (eg, substitution, dispensing errors) between Aristada and Aristada Initio may occur
• Aristada Initio is intended only for single administration
• Do not substitute Aristada Initio for Aristada because of differing pharmacokinetic profiles

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

Drug interaction overview

• See Dosage Modifications
• Strong CYP3A4 and CYP2D6 inhibitors: Coadministration of oral aripiprazole with strong CYP3A4 or CYP2D6 inhibitors increased the exposure of aripiprazole compared to the use of oral aripiprazole alone
• Strong CYP3A4 inducers: Coadministration of oral aripiprazole with strong CYP3A4 inducers decreased the exposure of aripiprazole compared to the use of oral aripiprazole alone
• Antihypertensives: Due to its alpha adrenergic antagonism, aripiprazole may potentiate the effects of certain antihypertensive agents; avoid concomitant use with Aristada Initio
• Benzodiazepines: Orthostatic hypotension and the intensity of sedation was greater with the combination of oral aripiprazole and lorazepam as compared to that observed with aripiprazole alone; avoid concomitant use with Aristada Initio

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; there are reports of poor weight gain in breastfed infants exposed to aripiprazole and reports of inadequate milk supply in lactating women taking aripiprazole; 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.

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

Aristada Initio

• Prodrug of aripiprazole and its activity is primarily due to aripiprazole, and to a lesser extent dehydro-aripiprazole (major metabolite of aripiprazole), which has been shown to have affinities for D2 receptors similar to aripiprazole and represents 30-40% of the aripiprazole exposure in plasma

Absorption

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

Peak plasma time: 1-3 hr (IR); 5-7 hr (ER); 3-5 hr (tablet); ~27 days (Aristada Initio)

Distribution

Protein bound: 99%

Vd: 404 L (aripiprazole IV); 268 L (Aristada Initio)

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)

Half-life, Aristada Initio: 15-18 days

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

Oral Administration

Oral solution can be substituted for tablets on a mg-per-mg basis up to the 25 mg dose level; patient receiving 30 mg tablets should receive 25 mg of solution

Tablet

• May take with or without food
• Swallow tablet whole; do not divide, crush, or chew

ODT

• Dosing for orally disintegrating tablets (ODT) is the same as for the oral tablets
• May take with or without food
• Do not open the blister until ready to take the ODT
• Remove 1 ODT by opening the package and peeling back the foil on the blister to expose the tablet
• Do not push the tablet through the foil because this could damage the tablet
• Immediately upon opening the blister, using dry hands, remove the tablet and place the entire ODT on tongue
• Tablet disintegration occurs rapidly in saliva; recommended to take without liquid, however, if needed, it can be taken with liquid
• Do not attempt to split the tablet

Abilify MyCite

• May take with or without food
• Swallow tablet whole; do not divide, crush, or chew

• MyCite Patch

  • Apply the MyCite patch only when instructed by the app to the left side of the body just above the lower edge of the rib cage
  • Do not place the patch in areas where the skin is scraped, cracked, inflamed, or irritated, or in a location that overlaps the area of the most recently removed patch
  • Instruct patients to keep the patch on when showering, swimming, or exercising
  • Change patch weekly or sooner as needed
  • The app will prompt patient to change the patch and will direct patient to apply and remove the patch correctly
  • Patients undergoing an MRI need to remove their patch and replace with a new one as soon as possible
  • If there is skin irritation, instruct patients to remove the patch

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 syringe at least 10 times to dislodge any material which may have settled

Shake the syringe vigorously for a minimum of 30 secs to ensure a uniform suspension; if the syringe is not used within 15 min, shake again for 30 secs

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 Preparation (Aristada Initio)

Tap syringe at least 10 times to dislodge any material which may have settled

Shake the syringe vigorously for a minimum of 30 secs to ensure a uniform suspension

If syringe is not used within 15 min, shake again for 30 secs

Injection site and associated needle length

• Deltoid: 21 gauge, 1-in or 20 gauge 1.5-in
• Gluteal: 20 gauge, 1-in or 20 gauge 1.5-in

Attach appropriate needle securely with a clockwise twisting motion; do NOT overtighten; overtightening could lead to needle hub cracking

Prime syringe to remove air

Bring syringe into upright position and tap the syringe to bring air to the top Inject in a rapid and continuous manner

Product requires a RAPID injection; do not hesitate

Administer the entire content IM; do not inject by any other route

Dispose of needle and any unused items

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

• Missed doses (Abilify Maintena)

  • 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

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

Missed doses (Aristada)

• 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 OR single dose of Aristada Initio
  • >7 wk: Supplement with 21 days of PO aripiprazole OR reinitiate with a single dose of Aristada Initio and a single dose of aripiprazole 30 mg PO

• 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 OR single dose of Aristada Initio
  • >12 wk: Supplement with 21 days of PO aripiprazole OR reinitiate with a single dose of Aristada Initio and a single dose of aripiprazole 30 mg PO

• 1064 mg q2mo

  • ≤10 wk: No PO supplementation required
  • >10 wk and ≤12 wk: Supplement with 7 days of PO aripiprazole OR single dose of Aristada Initio
  • >12 wk: Supplement with 21 days of PO aripiprazole OR reinitiate with a single dose of Aristada Initio and a single dose of aripiprazole 30 mg PO

Storage

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

Abilify Maintena (prefilled dual chamber syringe): Store below 30°C (86°F); 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 25°C (77°F), excursions permitted between 15- 30°C (59-86°F)

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

Aristada Initio: Store at room temperature 20-25°C (68-77°F) with excursions permitted between 15-30°C (between 59-86°F); do not freeze

Abilify MyCite

• Tablets

  • Store 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
  • Do not store in humid conditions (eg, bathroom)

• Patch (wearable sensor)

  • Store between 15-30°C (59-86°F) and 15-93% relative humidity