Aripiprazole (Abilify) is an atypical antipsychotic medicine that is used to treat a variety of mental disorders.

It is used to treat patients with the following disorders:

Oral use of aripiprazole:

• Acute and maintenance treatment of schizophrenia;

• acute (manic and mixed episodes) and maintenance treatment of bipolar I disorder as monotherapy or as an adjunct to lithium or valproic acid;

• adjunctive treatment of major depressive disorder;

• treatment of irritability associated with autistic disorder

Injection:

• Agitation and aggression associated with schizophrenia or bipolar I disorder (Abilify®);

• treatment of schizophrenia (Abilify Maintena™)

Unlabeled use of Aripiprazole: 

• Depression with psychotic features;

• aggression (children);

• conduct disorder (children);

• Tourette syndrome (children);

• pervasive developmental disorder not otherwise specified (PDD-NOS) (children);

• Asperger's Disorder (children);

• psychosis/agitation related to Alzheimer's dementia.

Aripiprazole Dose in Adults

Dose in the treatment of Schizophrenia:

• The 675 mg strength aripiprazole lauroxil can only be used as a single dose in combination with oral aripiprazole for initiation in long-term treatment with aripiprazole lauroxil.
• It can also be used as a single dose to restart treatment after a missed dose of aripiprazole lauroxil.
• It is not proposed for repeat dosing.

Intramuscular: Note:

• Tolerability should be developed with oral aripiprazole before initiating treatment with aripiprazole lauroxil (can take up to 14 days).
• Starting dosing options include a single day oral overlapping with 2 injections (Aristada Initio and Aristada).

or

• A 21-day oral overlap with 1 injection (Aristada).
• The 675 mg strength aripiprazole lauroxil (Aristada Initio) cannot be interchanged with other aripiprazole lauroxil strengths (Aristada).

• Initial dosage :

  • 1-day oral overlap:

    • Give a single oral aripiprazole 30 mg dose, along with single aripiprazole lauroxil (Aristada Initio) 675 mg dose, plus the first dose of aripiprazole lauroxil (Aristada) according to current oral aripiprazole dose  with or within 10 days aftergiving the 675 mg dose.

  • 21-day oral overlap:

    • Start Oral aripiprazole for 21 consecutive days alongwith first dose of aripiprazole lauroxil (Aristada) according to current oral aripiprazole dose.

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    Conversion of oral aripiprazole to I/M aripiprazole lauroxil (Aristada):

    • Oral aripiprazole 10 mg/day can be substituted with I/M aripiprazole lauroxil (Aristada) dose, 441 mg per month
    • Oral aripiprazole 15 mg/day can be substituted with various I/M aripiprazole lauroxil (Aristada) dosages:
      • 662 mg per month        or
      • 882 mg every 6 weeks    or
      • 1,064 mg every 2 months
• Oral aripiprazole more than 20 mg/day equals  882 mg/month of intramuscular aripiprazole lauroxil (Aristada) dose

• Adjustment of Dosage

  • Dose can be adjusted as needed
  • If a dose has to be given earlier than the recommended interval(s) then do not administer <2 weeks after the previous injection.

• Missed dose:

  • Give a missed dose as early as possible.
  • Supplementation with the 675 mg strength aripiprazole lauroxil (Aristada Initio) and/or oral aripiprazole is sometimes required,
  • In patients who take medicine orally, the same dose of oral aripiprazole is given that the patient was using before starting aripiprazole lauroxil unless otherwise indicated.

Concomitant Supplementation Recommendations Following Missed Doses

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  Dosage adjustment for concomitant therapy:

  • Patients starting treatment with aripiprazole lauroxil (Aristada) or restarting treatment with aripiprazole lauroxil (Aristada) after a missed dose:

  • 675 mg strength aripiprazole lauroxil (Aristada Initio) should be avoided in patients who are CYP2D6 poor metabolizers

                                     or

• In patients using aripiprazole lauroxil (Aristada) 441 mg, no dosage adjustment necessary, if tolerated.

• Initiation of a CYP3A4 inducer is planned for ≥2 weeks:

  • In patients receiving aripiprazole lauroxil (Aristada) 441 mg, build up the dose to 662 mg.
  • No dose adjustment is necessary for patients receiving aripiprazole lauroxil (Aristada) 662 mg, 882 mg, or 1,064 mg.

Aripiprazole (Abilify) dose in Children: 

Note:

• The Oral solution may be substituted for the oral tablet on an mg-per-mg basis, up to 25 mg.
• Children on 30 mg tablets should be given 25 mg oral solution.
• Orally disintegrating tablets (Abilify Discmelt®) and the immediate-release tablets (Abilify®) are bioequivalent.

Children and Adolescents:

Attention-Deficit/ Hyperactivity Disorder (ADHD):

• Children ≥8 years and Adolescents: Oral:
  • 2.5 mg/day initially;
  • The dose may be increased on a weekly basis by 2.5 mg/day increments as tolerated.
  • The maximum daily dose: 10 mg/day.

Autism; treatment of associated irritability (including aggression, deliberate self-injurious behavior, temper tantrums, and quickly changing moods): 

• Children and Adolescents 6-17 years:

  • 2 mg orally daily for 7 days initially, followed by 5 mg daily
  • The dose may be increased in increments of 5 mg at weekly intervals up to a maximum dose of 15 mg/day.

Bipolar I disorder (acute manic or mixed episodes): 

• Children and Adolescents 10-17 years:
  • 2 mg orally daily for 2 days, followed by 5 mg daily for 2 days with a further increase to the target dose of 10 mg daily
  • The dose may be increased in increments of 5 mg at weekly intervals up to a maximum daily dose of 30 mg/ day.

Conduct disorder and aggression:

• Children ≥6 years and Adolescents: Oral:

  • Patient weight <25 kg:

    • 1 mg/day;

  • 25-50 kg:

    • 2 mg/day;

  • 51-70 kg:

    • 5 mg/day;

  • >70 kg:

    • 10 mg/day;
  • The dose may be titrated after 2 weeks.
  • The maximum daily dose: 15 mg/ day.

Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) or Asperger's Disorder; treatment of associated irritability (aggression, self-injury, tantrums): 

• Children ≥4 years and Adolescents: Oral:

• Preschool age:

  • 1.25 mg/day initially.
  • The dose may be titrated every 5th day in increments of 1.25 mg/day if tolerated.

• Prepubertal children:

  • 1.25-2.5 mg/day orally initially with titration every 3-5 days in 1.25-2.5 mg/day increments as tolerated or clinically indicated
  • The maximum daily dose is 15 mg/ day.

• Adolescents:

  • 2.5-5 mg/day initially with titration every 5 days in 2.5-5 mg/day increments as tolerated or clinically indicated.
  • doses greater than 5 mg/day were divided twice daily.
  • if sleep disorder was reported, the dose was given in the morning and/ or at lunchtime.
  • The maximum daily dose is 15 mg/ day.

Schizophrenia: 

• Adolescents 13-17 years:

  • 2 mg orally daily for 2 days, followed by 5 mg daily for 2 days with a further increase to the target dose of 10 mg daily.
  • The dose may be increased in increments of 5 mg at weekly intervals to a maximum daily dose of 30 mg/ day.

Tourette's syndrome, tic disorders:

• Children ≥7 years and Adolescents:
  • 1.25-5 mg/day orally initially
  • The daily doses were increased by 1.25 - 2.5 mg weekly or by 5 mg every 2 weeks.
  • The maximum daily dose: 20 mg/day.

Aripiprazole (Abilify) pregnancy Risk Factor: C

• Antipsychotics used in the last trimester are a risk factor for abnormal movement in newborns.
• Data collection is ongoing to monitor the outcomes of infants and pregnant women after exposure to aripiprazole.
• Aripiprazole crosses the placenta. Aripiprazole as well as dehydro-aripiprazole may be detected in cord blood during delivery.
• The symptoms of a newborn's condition include agitation and feeding disorder, hypotonia, hypertonia or respiratory distress, somnolence, tremor, respiratory distress, and somnolence.
• It is a good idea to have healthcare providers register pregnant women who are exposed to aripiprazole lactil.

Use of Aripiprazole during breastfeeding

• Breast milk contains Aripiprazole.
• Before initiating therapy, it is important to consider the maternal health and the potential for drug exposure in the child's milk.

Aripiprazole Dose in Renal Disease:

• No dosage adjustment necessary.

Aripiprazole Dose in Liver Disease:

• No dosage adjustment necessary. 

Common Side Effects of Aripiprazole (Abilify) Include:

• Central nervous system:

  • Akathisia

Less Common Side Effects of Aripiprazole (Abilify) Include:

• Central nervous system:

  • Headache
  • Parkinsonian-like syndrome
  • Insomnia
  • Restlessness
  • Dystonia

• Endocrine & metabolic:

  • Weight gain

• Local:

  • Pain at the injection site

• Neuromuscular & skeletal:

  • Increased creatine phosphokinase

Rare side effects of aripiprazole (Abilify):

• Cardiovascular:

  • Angina Pectoris
  • Palpitations
  • Tachycardia

• Central nervous system:

  • Anxiety
  • Dizziness
  • Myasthenia

• Gastrointestinal:

  • Constipation
  • Xerostomia

• Neuromuscular & skeletal:

  • Asthenia

Contraindication to Aripiprazole Include:

• Allergy reactions that may be anaphylaxis or pruritus or urticaria to aripiprazole, or any component thereof, can occur.

Warnings and precautions

• Modified cardiac conduction
  • It can also alter the cardiac conduction.
  • Therapeutic doses of antipsychotics have been shown to cause life-threatening arrhythmias.
• Blood dyscrasias
  • In clinical trials and postmarketing reports, leukopenia, neutropenia and sometimes fatal agranulocytosis were reported.
  • Periodic blood count assessments should be performed if there are any risk factors, such as low WBC/ANC and preexisting drug-induced leukopenia/neutropenia.
  • Stop treatment at the first sign of blood dyscrasias, or if your absolute neutrophil count is 1,000/mm3.
• Effects on the cerebrovascular system:
  • In placebo-controlled studies of antipsychotics approved for use in dementia-related psychosis patients, there was a higher chance of cerebrovascular effects (eg stroke, transient ischemic attacks, stroke) than in those who were not prescribed.
• Depression in the CNS:
  • It can lead to CNS depression that may cause impairment of mental or physical abilities.
  • It is important to warn patients about tasks that require mental alertness, such as driving or operating machinery.
• Dyslipidemia
  • Lipid changes have been observed in the form of increases in total cholesterol and LDL cholesterol as well as triglycerides, and decreases in HDL cholesterol.
  • The risk of dyslipidemia is low compared to other antipsychotics.
• Esophageal dysmotility/aspiration
  • Aspiration and esophageal dysmotility have been linked to antipsychotic use;
  • As we age, the risk of developing cancer increases.
  • Patients at high risk of aspiration pneumonia (eg Alzheimer's disease) should be treated with caution, especially patients over 75 years.
• Extrapyramidal symptoms
  • It can cause extrapyramidal reactions (EPS), such as pseudo-parkinsonism and acute dystonic reactions. These reactions are generally less common than those caused by conventional antipsychotics. The frequency of these reactions has been reported to be similar to that of placebo.
  • Higher doses of antipsychotics, conventional antipsychotics, men, and younger patients are all associated with greater risk of dystonia (and possibly other EPS).
  • There are several factors that could be linked to tardive dyskinesia.
    • Old age
    • Pseudo-parkinsonism symptoms
    • Female gender and postmenopausal status combined,
    • Parkinson disease
    • Affective disorders, especially major depressive disorder,
    • Concurrent medical conditions such as diabetes and hypertension are also possible.
    • Previous brain damage
    • Alcoholism
    • Poor treatment and unsatisfactory results are the main reasons for u
    • Use of high doses antipsychotics
  • You may consider discontinuing therapy if you experience tardive dyskinesia symptoms.
• Falls
  • It can increase the chance of falling due to somnolence and orthostatic hypotension as well as motor or sensory instability.
  • Before and during treatment, patients should be evaluated for falls.
• Hyperglycemia
  • Hyperglycemia can be caused by antipsychotics that are not typical.
  • Hyperglycemia can be severe in some cases and may lead to hyperosmolar or even death.
  • Hyperglycemia symptoms (eg, polydipsia and polyuria), should be checked on all patients.
  • Patients with diabetes and other disorders of glucose regulation should be cautious; closely monitor for signs of a worsening glucose control.
  • Patients at high risk for diabetes (eg obesity or family history), should have a baseline fasting sugar (FBS), and periodic glucose regulation assessments.
  • The treatment for hyperglycemia may be stopped. However, some patients will need to be treated for diabetes after the therapy is stopped.
  • Aripiprazole Lauroxil has a very low risk of hyperglycemia compared to other antipsychotics.
• Disorders of impulse control:
  • Compulsive behavior and/or loss in impulse control have been linked to it.
  • These include uncontrolled gambling, pathological sexual urges, uncontrolled spending and binge/compulsive eating.
  • Patients who have had a history of impulse control problems may be at greater risk.
  • These behaviors can be reversed by stopping or reducing dosages of therapy, although not always.
• Neuroleptic malignant Syndrome:
  • Its use could be linked to the neuroleptic malignant disorder (NMS).
  • Monitor for changes in mental status, fever, rigidity of muscles, and/or autonomic instability.
• Orthostatic hypotension
  • It can lead to orthostatic hypotension.
  • The risk of developing an infection is higher during the first treatment or dose escalation.
  • Patients at high risk for this effect and those who cannot tolerate temporary hypotensive episodes (cerebrovascular Disease, cardiovascular Disease, Hypovolemia) should be cautious.
  • These patients may benefit from lower starting doses and slower titrations.
• Temperature regulation
  • It is possible to have impaired core body temperature regulation
  • Patients who do strenuous exercise, are exposed to heat or are at risk of dehydration and those taking anticholinergic medications should be aware that the drug can cause serious side effects.
• Weight loss
  • Antipsychotic therapy has led to significant weight gain; incidences vary from product to product.
  • It is recommended to monitor your weight.
  • Aripiprazole is much less likely to cause weight gain than other antipsychotics.
• Cardiovascular disease
  • Patients with cerebrovascular disease, cardiac disease, pre-myocardial infarction, ischemic hearts disease, and patients with prior myocardial injury should be cautious.
• Dementia [US Boxed Warning]
  • Antipsychotics pose a higher risk of death for dementia-related psychosis patients than placebo.
  • The majority of deaths were caused by either infectious (eg pneumonia) or cardiovascular problems in nature.
  • Patients with Parkinson disease dementia or Lewy body dementia should be cautious about using this medication.
  • There is a greater risk of adverse reactions, increased sensitivity for extrapyramidal effects and association with irreversible cognitive decline or death.
  • It is not approved to treat dementia-related psychosis.
• Parkinson disease
  • Patients with Parkinson's disease should be treated with caution
  • Motor disturbances can be aggravated by antipsychotics.
• Seizures
  • Patients at high risk of seizures should be treated with caution, especially those who have had seizures in the past, are brain damaged, suffered from head trauma or have been drinking, and/or are receiving concurrent treatment with medication that could lower their seizure threshold.
  • Due to the increased prevalence of predisposing conditions, elderly patients may be more susceptible to seizures.

Aripiprazole (oral and [Abilify Maintena] long-acting injectable): Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor:

• Mental health

• Vital signs

• Blood pressure baseline after 3 months of antipsychotics and annually thereafter.

• At baseline, weight, height, BMI and waist circumference were at 4, 8 and 12 weeks following the start or change of therapy. Then, quarterly.

  • If the patient experiences a greater than 5% weight gain, he or she should switch to another antipsychotic.

• Patients with low WBC, or a history of drug-induced neutropenia or leukopenia should have their CBC checked frequently in the first few months.

• Annual serum electrolytes and liver function tests are recommended.

• At baseline, and 3 months after starting therapy, fasting plasma glucose and glycated haglobin should be performed. Then, every year.

• Fasting lipid profile should also be taken at baseline and three months after starting therapy.

• If the LDL levels are normal, they can be repeated every 2 to 5 years or more if it is clinically necessary.

• Every year, it is important to monitor changes in menstruation, fertility, libido and the development of galactorrhea and erectile function.

• Monitor your patient for symptoms of Parkinson's disease, parkinsonian symptoms, and abnormal involuntary movements weekly up to the time the dose is stabilized. This should be done for at least 14 days after the introduction as well as for 2 weeks after any significant dose increases.

• High-risk patients should have their tardive dyskinesia checked at least once a year.

• Patients over 40 years old should have their eyes examined every year, and younger patients should have it done every 2 years.

How to administer Aripiprazole (Abilify)?

• Only for intramuscular administration
• In the deltoid, gluteal or gluteal muscles, give the 441 mg (Aristada), and the 675mg (Aristada Initio). Also give other dose strengths (Aristada).
• It is administered in a continuous and rapid manner.

• Do not give two aripiprazole injections simultaneously (Aristada Initio and Aristada) in the same muscle.

• To ensure uniform suspension, tap the syringe at minimum 10 times before administering. Next, shake the syringe vigorously for >=30 seconds.
• Do not use the syringe for more than 15 minutes. Instead, shake it again for 30 seconds.

• The needle should be the right size for the injection site.

  • A 21-gauge 1 inch needle or a 20-gauge 1.5-inch, 1-inch needle are available for deltoid injections.

  • A 20-gauge, 1.5 or 2-inch needle is required for gluteal injection.

• Patients with more subcutaneous tissue than the injection site muscles should use the longer needles.

Mechanism of action of Aripiprazole (Abilify):

• Aripiprazole Lauroxil is a protodrug for aripiprazole.
• Aripiprazole lacil is converted likely by enzyme-mediated hydrolysis into N-hydroxymethyl aripiprazole following an IM injection.
• This is then hydrolyzed and made to aripiprazole.
• It is a quinolinone-antimpsychotic that has a high affinity to D2, D3, 5-HT-1A and 5-HT-2A receptors.
• It also has moderate affinity for D-4 and 5-HT-2C receptors.
• It has moderate affinity for serotonin receptor transporter.
• It does not have an affinity for muscarinic or cholinergic receptors.
• Aripiprazole is a partial agonist for the D-2 and 5-HT-1A receptors and an antagonist for the 5-HT receptor.

The beginning of action: Aristada can be administered 5-6 days after injection and within 4 days if taken concomitantly to oral aripiprazole.

Aristada Initio (75 mg strength) It reaches the systemic circulation within a few hours of injection. When administered with oral aripiprazole 30, mg, it reaches clinically relevant serum levels 4 days after injection.

Time of action: Aristada 36 days after systemic circulation.

Protein binding: More than 99%, primarily due to albumin

Metabolism:

• It is subject to enzyme-mediated hydrolysis at N-hydroxymethyl Aripiprazole, followed by enzymemediated hydrolysis at aripiprazole.
• Aripiprazole is subject to hepatic metabolism mainly through CYP2D6 and CYP3A4. (Dehydro-aripiprazole metabolite) has an affinity for D receptors that are similar to the parent drugs and accounts for 40% of parent drug exposure in plasma

Eliminating half-life Aristada: 53.9 to 57.2 days Aristada Initio (75 mg strength): 15-18 days

Time until peak serum concentrations are reached: Aristada Initio (375 mg strength): 16-35 days (median 27 Days)

International Brands of Aripiprazole:

• Aristada
• Aristada Initio
• Abilify Discmelt
• Abilify Maintena
• Abilify

Aripiprazole brands in Pakistan: