Aripiprazole

Aripiprazole is a prescription medication used in treatment of schizophrenia, bipolar mania, and major depressive disorder.

• Extended-release aripiprazole injection is used to treat a mental/mood disorder called schizophrenia. This medication can decrease hallucinations (hearing/seeing things that are not there) and improve your concentration. It also helps you to think more clearly, feel less nervous, and take a more active part in everyday life. Extended-release aripiprazole injection is a long-acting psychiatric medication known as an atypical antipsychotic. It works by helping to restore the balance of certain natural substances in the brain.
• Aripiprazole is available under the following different brand names: Abilify, Abilify Maintena, and Aristada.

Adult and pediatric dosages:

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

Tablet, orally disintegrating

• 2 tabs (6.78 mg) orally three times daily

Aripiprazole pallida root tincture

• 10 mg
• 15 mg

Oral solution

• 1 mg/ml

Adult dosages only:

The extended-release injectable intermuscular suspension (Abilify Maintena)

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

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

• 441 mg/prefilled syringe
• 662 mg/prefilled syringe
• 882 mg/prefilled syringe

Injectable intermuscular solution

• 7.5 mg/ml (9.75 mg/1.3 ml)

Dosage Considerations – Should be Given as Follows:

Schizophrenia

Adult Dosages

• 10-15 mg/day orally initially, may be increased to 30 mg/day orally after 2 weeks

Maintenance with Abilify Maintena

• 400 mg intramuscularly once monthly; continue treatment with aripiprazole orally (10-20 mg/day) or another oral antipsychotic for 14 consecutive days following the first injection
• Only to be administered by deep intermuscular injection into the deltoid or gluteal muscle by a healthcare professional
• Establish tolerability with oral aripiprazole prior to initiating if the patient has never taken aripiprazole
• Administer monthly dose no sooner than 26 days after the previous injection (also see Dosage Modifications)
• Consider dose reduction to 300 mg/month if adverse reaction occurs

Treatment of relapse with Abilify Maintena

• 400 mg intermuscular plus oral aripiprazole 10-20 mg for 2 weeks

Aristada

• Establish tolerability to aripiprazole with oral dosing, then in conjunction with the first Aristada dose, administer treatment with oral aripiprazole for 21 consecutive days
• Depending on individual patient's needs, treatment can be initiated with 441 mg, 662 mg, or 882 mg intramuscularly once monthly of Aristada, which corresponds to 300 mg, 450 mg, and 600 mg of aripiprazole base, respectively
• Treatment may also be initiated with 882 mg intramuscularly every 6 weeks
• 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
• Aristada dose based on a total oral dose
  • 10 mg/day orally: 441 mg intramuscularly once monthly
  • 15 mg/day orally: 662 mg intramuscularly once monthly
  • Over 20 mg/day: 882 mg intramuscularly once monthly

Pediatric Dosages

• 13-17 years: 2 mg/day orally initially; increased to 5 mg/day after 2 days; increased to recommended dosage of 10 mg/day after additional 2 days; may subsequently be increased by 5 mg/day; maintenance: 10-30 mg/day

Bipolar Mania

Adult Dosages

• Acute and maintenance treatment of manic or mixed episodes associated with bipolar I disorder, either as monotherapy or as an adjunct to lithium or valproate
• Monotherapy: 15 mg/day orally initially; may be increased gradually; not to exceed 30 mg/day
• Adjunct to lithium or valproate: 10-15 mg/day orally 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 over 6 weeks not studied

Pediatric Dosages

• Acute manic or mixed episodes, either as monotherapy or as an adjunct to lithium or valproate
• Children 10-17 years: 2 mg/day orally initially; increased to 5 mg/day after 2 days; increased to recommended dosage of 10 mg/day after additional 2 days; may subsequently be increased by 5 mg/day; maintenance: 10-30 mg/day

Major Depressive Disorder

Adult Dosages

• 2-5 mg/day orally initially; increased weekly as needed by over or equal to 5 mg/day to a dose range of 2-15 mg/day
• Used adjunctively with other antidepressants

Dosage Modifications (Oral)

Adult Dosages

• 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 (decrease dose by 75%)
• Coadministration with any CYP2D6 inhibitor PLUS any CYP3A4 inhibitor: Decrease dose to 25% of the usual dose (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 (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)

Adult Dosages

• CYP2D6 poor metabolizers: 300 mg intramuscularly
• CYP2D6 poor metabolizers taking concomitant CYP3A4 inhibitor: 200 mg intramuscularly

Patients taking 400 mg intramuscularly

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

Patients taking 300 mg intramuscularly

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

Missed doses

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

Dosage Modifications (Aristada)

Adult Dosages

• No dosage changes if CYP450 modulators are added for less than 2 weeks
• Strong CYP3A4 inhibitor for over 2 weeks
• Reduce the dose to the next lower strength no dosage adjustment is necessary for patients taking 441 mg if tolerated
• Poor CYP2D6 metabolizers: Reduce dose to 441 mg from 662 mg or 882 mg; no dosage adjustment necessary in patients taking 441 mg if tolerated
• Strong CYP2D6 inhibitor for more than 2 weeks
• Reduce the dose to the next lower strength
• No dosage adjustment is necessary for patients taking 441 mg if tolerated
• Poor CYP2D6 metabolizers: No dose adjustment required
• Both strong CYP3A4 and CYP2D6 inhibitors for over 2 weeks
• Avoid use for patients taking 662 mg or 882 mg
• No dosage adjustment is necessary for patients taking 441 mg if tolerated
• CYP3A4 inducers for over 2 weeks
• No dose adjustment for 662 mg and 882 mg dose
• 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 exceeded 6-8 weeks
• See the following for recommendations for missed doses based on the last injection dose

Monthly 441 mg

• Up to 6 weeks: No oral supplementation is required
• Over 6 weeks and up to 7 weeks: Supplement with 7 days of oral aripiprazole
• Over 7 weeks: Supplement with 21 days of oral aripiprazole
• Monthly 662 mg, monthly 882 mg, or 882 mg every 6 weeks
• Up to 8 weeks: No oral supplementation is required
• Over 8 weeks and up to 12 weeks: Supplement with 7 days of oral aripiprazole
• Over 12 weeks: Supplement with 21 days of oral aripiprazole

Autism

Pediatric Dosages

• Irritability associated with autistic disorder
• Children under 6 years: Safety and efficacy not established
• Children 6-17 years: 2 mg/day orally initially; increased gradually at intervals over or 1 week to target dosage of 5 mg/day; may gradually be further increased as needed to 10 mg/day or higher; not to exceed 15 mg/day

Tourette Disorder

Pediatric Dosages

Indicated for the treatment of Tourette disorder

• Children under 6 years: Safety and efficacy not established
• Children 6-18 years (less than 50 kg)

Initiate at 2 mg/day orally 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

Children 6-18 years (over or 50 kg)

• Initiate at 2 mg/day orally 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)

Pediatric Dosage

• 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 (decrease dose by 75%)
• Coadministration with any CYP2D6 inhibitor PLUS any CYP3A4 inhibitor: Decrease dose to 25% of the usual dose (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 (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

Side effects of aripiprazole include:

• weight gain
• headache
• agitation
• anxiety
• nausea
• vomiting
• lightheadedness
• constipation
• dizziness
• indigestion
• sleepiness
• fatigue
• restlessness
• shakiness (tremor)
• dry mouth
• extrapyramidal disorder (EPS) (muscle spasms, restlessness, muscle rigidity, slowness of movement, tremor, and jerky movements)
• feeling dizzy when standing up
• musculoskeletal stiffness
• abdominal discomfort
• blurred vision
• cough
• pain
• muscle pain
• rash
• stuffy nose
• altered mental status
• fever above 106.7 degrees
• muscle rigidity
• neuroleptic malignant syndrome (NMS)
• stiff jerky movements
• fever
• confusion
• fast or uneven heartbeats
• sudden numbness or weakness
• poor balance
• difficulty speaking
• flu symptoms
• sores in the mouth or throat
• increased thirst
• increased urination
• loss of appetite
• fruity breath odor
• dry skin
• seizures
• thoughts of hurting yourself
• yellowing of skin or eyes (jaundice)
• decreased urination
• difficulty falling asleep (insomnia)

Postmarketing side effects of Aripiprazole reported include:

• pathological gambling
• hiccups
• falls

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Aripiprazole has no known severe interactions with other drugs.
• Aripiprazole has serious interactions with at least 28 different drugs.
• Aripiprazole has moderate interactions with at least 334 different drugs.
• Aripiprazole has minor interactions with at least 29 different drugs.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns, or for more information about this medicine.

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 (heart failure, sudden death) or infectious (pneumonia) in nature
• In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (under 24 years of age) taking antidepressants for major depressive disorders and other psychiatric illnesses
• This medication contains aripiprazole. Do not take Abilify, Abilify Maintena, or Aristada if you are allergic to aripiprazole or any ingredients contained in this drug
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately

Contraindications

• Documented hypersensitivity

Effects of Drug Abuse

• No information available

Short-Term Effects

• In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (under 24 years of age) taking antidepressants for major depressive disorders and other psychiatric illnesses
• See "What Are Side Effects Associated with Using Aripiprazole?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Aripiprazole?"

Cautions

• Risk of NMS and extrapyramidal symptoms (EPS)
• Stiff, jerky movements may occur; may consider discontinuation of therapy if clinically indicated
• May cause sleepiness, low blood pressure after standing for at least a minute, 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 low blood pressure; may increase the incidence of cerebrovascular adverse reactions (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 fainting
• Use caution in patients with Parkinson's 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
• Leukopenia/neutropenia and agranulocytosis were reported; possible risk factors for leukopenia/neutropenia include preexisting low white blood cell (WBC) count and a history of drug-induced leukopenia/neutropenia
• If the patient has a history of clinically significant low white blood cell count or drug-induced leukopenia/neutropenia, monitor complete blood count (CBC) frequently during the first few months of therapy; discontinue the drug at the first sign of clinically significant white blood cell decline under 1000/mcL in absence of other causative factors, and continue monitoring white blood cell count until recovery
• Monitor for an increase in blood pressure after standing up (orthostatic hypertension)
• May cause seizures or convulsions; use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold
• May cause central nervous system 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
• 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 high blood sugar (hyperglycemia) and diabetes; in some cases, hyperglycemia concomitant with the use of atypical antipsychotics has been associated with deficient insulin production (ketoacidosis), severe dehydration (hyperosmolar coma), or death; monitor patients for symptoms of hyperglycemia including excessive thirst, abnormally large volume of dilute volume, excessive hunger, and weakness; monitor glucose regularly in patients with and at risk for diabetes
• Significant weight gain reported with therapy; monitor waist circumference and BMI

Pregnancy and Lactation

• Use aripiprazole during pregnancy with caution if benefits outweigh risks
• Animal studies show risk and human studies are not available, or neither animal nor human studies were done
• Aripiprazole is excreted in breast milk
• A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother