Generic Drug Therapeutic Class: Neurology-Psychiatry
active ingredients: Aripiprazole
laboratory: Otsuka Pharma Europe Ltd
Case of 98
ABILIFY is indicated for the treatment of schizophrenia in adults and adolescents aged 15 years and older.
ABILIFY is indicated for the treatment of moderate to severe manic episodes of bipolar I disorder and for the prevention of recurrence of manic episodes in adults with predominantly manic episodes and for whom manic episodes have responded to treatment. by aripiprazole (see section 5.1 Pharmacodynamic properties ).
ABILIFY is indicated for the treatment of moderate to severe manic episodes of bipolar I disorder in adolescents 13 years of age and older for up to 12 weeks (see section 5.1 ).
Dosage ABILIFY 10 mg Tablet Case of 98
Adults:Schizophrenia: The recommended starting dose of ABILIFY is 10 or 15 mg / day with a maintenance dose of 15 mg / day, once, during or after meals.
ABILIFY is effective in a dose range of 10 to 30 mg / day. An increase in efficacy for doses above the recommended 15 mg daily dose has not been demonstrated, however some patients may benefit from a higher dose. The maximum daily dose should not exceed 30 mg.
Manic Episodes in Bipolar I Disorders: The recommended starting dose for ABILIFY is 15 mg once daily during or after meals, monotherapy or combination therapy (see section 5.1 Pharmacodynamic properties ). Some patients may receive a higher dose. The maximum daily dose should not exceed 30 mg.
Prevention of recurrence of manic episodes in bipolar I disorder: For the prevention of recurrence of manic episodes in patients treated with aripiprazole monotherapy or combination, treatment will be maintained at the same dose. The daily dosage may be adapted, a dose reduction may be considered depending on the clinical condition of the patient.
Schizophrenia in Adolescents Aged 15 Years and Older: The recommended dose of ABILIFY is 10 mg / day administered once daily during or after meals. Treatment is initiated at a dose of 2 mg (using ABILIFY oral solution 1 mg / ml) for two days, titrated to 5 mg for two additional days to reach the recommended daily dosage of 10 mg. Depending on the case, the following dose increases are administered in 5 mg increments, without exceeding the maximum daily dosage of 30 mg (see section 5.1 ).
ABILIFY is effective between 10 to 30 mg / day. Increased efficacy at doses above the 10 mg daily dose has not been demonstrated, although each patient may benefit at a higher dose.
The use of ABILIFY is not recommended in schizophrenia patients under 15 years of age because the available data on safety and efficacy are insufficient (see sections 4.8 Undesirable effects and Pharmacodynamic properties ).
Manic episodes in bipolar I disorder in adolescents 13 years of age and older: the recommended dose of ABILIFY is 10 mg once daily in one dose with or without food. Treatment is initiated at a dose of 2 mg (using ABILIFY oral solution 1 mg / ml) for 2 days, titrated to 5 mg for 2 additional days to reach the recommended daily dosage of 10 mg.
The duration of treatment should be as short as necessary to control symptoms and should not exceed 12 weeks. Increased efficacy at doses above the 10 mg daily dose has not been demonstrated and a daily dose of 30 mg has been associated with a substantial increase in the incidence of significant adverse events including extrapyramidal symptoms (EPS), fatigue and weight gain (see section 4.8 ). Therefore, doses greater than 10 mg / day should be used for exceptional cases and associated with close clinical monitoring (see Warnings and Precautions, Adverse Reactions and Pharmacodynamic Properties sections).
Younger patients have a higher risk of developing adverse events associated with aripiprazole. Therefore, the use of ABILIFY is not recommended in patients younger than 13 years of age (see sections 4.8 Undesirable effects and Pharmacodynamic properties ).
Irritability associated with autistic disorder: The safety and efficacy of ABILIFY in children and adolescents under 18 years of age have not been established. The currently available data are described in the Pharmacodynamic properties section but no dosage recommendation can be made.
Hepatic impairment: No dose adjustment is required in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, there is insufficient data to make recommendations. Administration should be cautious in these patients. However, the maximum daily dose of 30 mg may be used with caution in patients with severe hepatic impairment (see section 5.2 ).
Patients with renal impairment: No dose adjustment is required in patients with renal impairment.
Elderly patients: The efficacy of ABILIFY in the treatment of schizophrenia and bipolar I disorder in patients aged 65 years and older has not been established. Due to the greater sensitivity of this population, a lower initial dose should be considered when clinical reasons warrant (see Warnings and Precautions ) section.
Gender: No dosage adjustment is required in women over men (see section 5.2 ).
Smokers: No dosage adjustment is required for smokers based on the metabolism of ABILIFY (see section 4.5 Interactions with other medicinal products and other forms of interaction ).
Dose adjustments related to interactions:
When concomitant use of strong CYP3A4 or CYP2D6 inhibitors with aripiprazole, the aripiprazole dose should be reduced. When the CYP3A4 inhibitor or CYP2D6 is discontinued, the aripiprazole dose should be increased (see section 4.5 ).
When co-administering CYP3A4 inducers with aripiprazole, the aripiprazole dose should be increased. When the CYP3A4 inducer is stopped, the aripiprazole dose should be reduced to the recommended dosage (see section 4.5 ).
ABILIFY tablets is for oral use.
Hypersensitivity to the active substance or to any of the excipients.
Abilify side effects
Adults:The most commonly reported adverse events in placebo-controlled clinical studies were akathisia and nausea, each occurring in more than 3% of patients treated with oral aripiprazole.
The following side effects have been reported more frequently (≥ 1/100) than placebo, or have been identified as clinically significant adverse events (*):
The frequencies below are defined using the following convention: frequent (≥ 1/100 to <1/10); uncommon (≥ 1/100 to <1/100).
Frequent: agitation, insomnia, anxiety
Uncommon: depression *
Nervous system disorders
Frequent: extrapyramidal disorders, akathisia, tremor, dizziness, somnolence, sedation,
Common: vision disorder
Uncommon: tachycardia *
Uncommon: orthostatic hypotension *
Common: dyspepsia, vomiting, nausea, constipation, salivary hypersecretion
General disorders and administration site conditions
Extrapyramidal symptoms: Schizophrenia: In a 52-week long-term controlled clinical trial, the incidence of extrapyramidal symptoms, including parkinsonism, akathisia, dystonia and dyskinesia, was lower overall in aripiprazole-treated patients (25.8%). %) compared to patients treated with haloperidol (57.3%). In a 26-week long-term, placebo-controlled clinical study, the incidence of extrapyramidal symptoms was 19% in the aripiprazole-treated patients and 13.1% in the placebo-treated patients. In another 26-week long-term controlled clinical study, the incidence of extrapyramidal symptoms was 14.8% in the aripiprazole-treated patients and 15.1% in the olanzapine-treated patients. Manic Episodes in Bipolar I Disorder - In a controlled clinical study at 12 weeks, the incidence of extrapyramidal symptoms was 23.5% in the aripiprazole-treated patients and 53.3% in the haloperidol-treated patients. In another clinical study at 12 weeks, the incidence of extrapyramidal symptoms was 26.6% in patients treated with aripiprazole and 17.6% in patients treated with lithium. In the long-term, placebo-controlled clinical study at 26 weeks of maintenance, the incidence of extrapyramidal symptoms was 18.2% in the aripiprazole-treated patients and 15.7% in the placebo-treated patients.
In placebo-controlled clinical studies, the incidence of akathisia in bipolar patients was 12.1% with aripiprazole and 3.2% with placebo. In schizophrenic patients, the incidence of akathisia was 6.2% with aripiprazole and 3.0% with placebo.
Dystonia: Class effect: symptoms of dystonia, prolonged abnormal contractions of a muscle group have been reported in patients predisposed during the first days of treatment. Dystonic symptoms include spasm of the neck muscles, sometimes progressing to oppression of the throat, difficulty swallowing, difficulty breathing, and / or protrusion of the tongue. While these symptoms may occur at low doses, they have been reported more frequently and with greater severity with high-potency and higher-dose first-generation antipsychotics. A high risk of acute dystonia has been observed in groups of men and youth.
Among patients who experienced changes in standard and lipid parameters that could be clinically significant (see section 5.1 ), there was no significant difference in clinical status between the aripiprazole group and the placebo group. Elevations of CPK (Creatine Phosphokinase), generally transient and asymptomatic, were observed in 3.5% of aripiprazole-treated patients and 2.0% of placebo-treated patients.
Adverse reactions known to be associated with antipsychotic medications have also been reported during treatment with aripiprazole (neuroleptic malignant syndrome, tardive dyskinesia, convulsions, cerebrovascular adverse events and increased mortality in elderly patients with dementia, hyperglycaemia and diabetes) (see section Warnings and precautions for use ).
In a short-term placebo-controlled clinical trial in 302 schizophrenic adolescents (aged 13 to 17 years), the frequency and nature of adverse events were similar to those of adults, with the exception of the following reactions that were reported more frequently in adolescents taking aripiprazole compared to adults taking aripiprazole (and more frequently than placebo): drowsiness / sedation and extrapyramidal disorder were very common (≥ 1/10), dry mouth, increased appetite and hypotension orthostatic have been reported frequently (≥ 1/100, <1/10). The safety profile in an open-label 26-week extension trial was similar to that seen in the short-term placebo-controlled trial. Pooled analysis of a population of adolescents (aged 13 to 17 years) with schizophrenia, exposed to the product for up to 2 years, reveals low plasma prolactin incidence in girls (<3 ng / ml) and boys (<2 ng / ml) of 29.5% and 48.3%, respectively.
Schizophrenia in adolescents aged 15 and over:
Manic episodes in bipolar I disorder in adolescents 13 years of age and older:
The frequency and nature of adverse reactions in adolescents with bipolar I disorder were similar to those seen in adults with the exception of the following: very frequently (≥ 1/10) drowsiness (23.0%) extrapyramidal disorders (18.4%), akathisia (16.0%) and fatigue (11.8%); frequently (≥ 1/100, <1/10) upper abdominal pain, increased heart rate, weight gain, increased appetite, muscle contractions and dyskinesia.
The following adverse events had a possible dose-effect relationship: extrapyramidal disorders (the incidence was 9.1% at a dose of 10 mg, 28.8% at a dose of 30 mg and 1.7% for placebo) ; and akathisia (the incidence was 12.1% at a dosage of 10 mg, 20.3% at a dosage of 30 mg and 1.7% for placebo).
Mean weight changes in adolescents with bipolar I disorder after 12 and 30 weeks of treatment were 2.4 kg and 5.8 kg with aripiprazole and 0.2 kg and 2.3 kg, respectively with the placebo.
In the pediatric population, somnolence and fatigue were observed more frequently in patients with bipolar disorder compared to those with schizophrenia.
In the pediatric population with bipolar disorder (patients aged 10 to 17 years), exposed to the product for periods up to 30 weeks, the incidence of low plasma prolactin levels was 28.0% in females ( <3 ng / ml) and 53.3% in boys (<2 ng / ml).
Adverse reactions reported after marketing:
The following side effects have been reported after marketing. The frequency of these
effects is considered unknown (can not be estimated from the available data).
Hematologic disorders and
leukopenia, neutropenia, thrombocytopenia
Immune system disorders:
allergic reactions (eg anaphylactic reaction,
Quincke's edema including swelling of the tongue,
edema of the tongue, edema of the face, pruritus or urticaria)
hyperglycemia, diabetes mellitus, ketoacidosis diabetes,
hyperosmolar diabetic coma
Metabolism disorders and
weight gain, weight loss, anorexia, hyponatremia
agitation, nervousness, pathological gambling; suicide attempt,
suicidal ideation, completed suicide (see Warnings and Precautions for Use section ).
Nervous system disorders:
slurred speech, neuroleptic malignant syndrome
(SMN), grand epilepticus, serotonin syndrome
QT prolongation, ventricular arrhythmia, sudden death
unexplained, cardiac arrest, torsades de pointes, bradycardia
syncope, hypertension, thromboembolic event
(including pulmonary embolism and venous thrombosis
Respiratory, thoracic disorders
Oropharyngeal spasm, laryngeal spasm, pneumonia
pancreatitis, dysphagia, discomfort in the abdomen, discomfort
stomach level, diarrhea
liver failure, jaundice, hepatitis, increased
alanine aminotransferase (ALT), increased
Aspartate aminotransferase (ASAT), increased
gamma glutamyl transferase (GGT), increased
Skin and tissue disorders
rash, photosensitivity reaction, alopecia, hyperhidrosis
Musculoskeletal disorders and
rhabdomyolysis, myalgia, stiffness
Negative drug withdrawal syndrome (see
Fertility, pregnancy and lactation section)
Kidney disorders and pathways
urinary incontinence, urinary retention
Disorders of organs of
reproduction and breast:
General disorders and abnormalities
disturbance of temperature regulation (eg
hypothermia, fever), chest pain, edema
Increased Creatine Phosphokinase, Increase
blood sugar levels, blood glucose