Abilify

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 5 mg tablets 
ABILIFY 10 mg tablets 
ABILIFY 15 mg tablets 
ABILIFY 30 mg tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
ABILIFY 5 mg tablets 
Each tablet contains 5 mg of aripiprazole. 
Excipient with known effect 
63.65 mg lactose (as monohydrate) per tablet 
 
ABILIFY 10 mg tablets 
Each tablet contains 10 mg of aripiprazole. 
Excipient with known effect 
59.07 mg lactose (as monohydrate) per tablet 
 
ABILIFY 15 mg tablets 
Each tablet contains 15 mg of aripiprazole. 
Excipient with known effect 
54.15 mg lactose (as monohydrate) per tablet 
 
ABILIFY 30 mg tablets 
Each tablet contains 30 mg of aripiprazole. 
Excipient with known effect 
177.22 mg lactose (as monohydrate) per tablet 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Tablet 
 
ABILIFY 5 mg tablets 
Rectangular and blue, engraved with "A-007" and "5" on one side. 
 
ABILIFY 10 mg tablets 
Rectangular and pink, engraved with "A-008" and "10" on one side. 
 
ABILIFY 15 mg tablets 
Round and yellow, engraved with "A-009" and "15" on one side. 
 
ABILIFY 30 mg tablets 
Round and pink, engraved with "A-011" and "30" on one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
ABILIFY is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years 
and older. 
 



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ABILIFY is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder 
and for the prevention of a new manic episode in adults who experienced predominantly manic 
episodes and whose manic episodes responded to aripiprazole treatment (see section 5.1). 
 
ABILIFY is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in 
Bipolar I Disorder in adolescents aged 13 years and older (see section 5.1). 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults 
 
Schizophrenia: the recommended starting dose for ABILIFY is 10 mg/day or 15 mg/day with a 
maintenance dose of 15 mg/day administered on a once-a-day schedule without regard to meals. 
ABILIFY is effective in a dose range of 10 mg/day to 30 mg/day. Enhanced efficacy at doses higher 
than a daily dose of 15 mg has not been demonstrated although individual patients may benefit from a 
higher dose. The maximum daily dose should not exceed 30 mg. 
 
Manic episodes in Bipolar I Disorder: the recommended starting dose for ABILIFY is 15 mg 
administered on a once-a-day schedule without regard to meals as monotherapy or combination 
therapy (see section 5.1). Some patients may benefit from a higher dose. The maximum daily dose 
should not exceed 30 mg. 
 
Recurrence prevention of manic episodes in Bipolar I Disorder: for preventing recurrence of manic 
episodes in patients, who have been receiving aripiprazole as monotherapy or combination therapy, 
continue therapy at the same dose. Adjustments of daily dosage, including dose reduction should be 
considered on the basis of clinical status. 
 
Paediatric population 
 
Schizophrenia in adolescents aged 15 years and older: the recommended dose for ABILIFY is 
10 mg/day administered on a once-a-day schedule without regard to meals. Treatment should be 
initiated at 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 dose of 10 mg. When appropriate, subsequent dose increases 
should be administered in 5 mg increments without exceeding the maximum daily dose of 30 mg (see 
section 5.1). ABILIFY is effective in a dose range of 10 mg/day to 30 mg/day. Enhanced efficacy at 
doses higher than a daily dose of 10 mg has not been demonstrated although individual patients may 
benefit from a higher dose. 
ABILIFY is not recommended for use in patients with schizophrenia below 15 years of age due to 
insufficient data on safety and efficacy (see sections 4.8 and 5.1). 
 
Manic episodes in Bipolar I Disorder in adolescents aged 13 years and older: the recommended dose 
for ABILIFY is 10 mg/day administered on a once-a-day schedule without regard to meals. Treatment 
should be initiated at 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 dose of 10 mg. The treatment duration should be the 
minimum necessary for symptom control and must not exceed 12 weeks. Enhanced efficacy at doses 
higher than a daily dose of 10 mg has not been demonstrated, and a daily dose of 30 mg is associated 
with a substantially higher incidence of significant adverse reactions including EPS related events, 
somnolence, fatigue and weight gain (see section 4.8). Doses higher than 10 mg/day should therefore 
only be used in exceptional cases and with close clinical monitoring (see sections 4.4, 4.8 and 5.1). 
Younger patients are at increased risk of experiencing adverse events associated with aripiprazole. 
Therefore, ABILIFY is not recommended for use in patients below 13 years of age (see sections 4.8 
and 5.1). 
 
Irritability associated with autistic disorder: the safety and efficacy of ABILIFY in children and 
adolescents aged below 18 years have not yet been established. Currently available data are described 



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in section 5.1 but no recommendation on a posology can be made. 
 
Tics associated with Tourette’s disorder: the safety and efficacy of ABILIFY in children and 
adolescents 6 to 18 years of age have not yet been established. Currently available data are described 
in section 5.1 but no recommendation on a posology can be made. 
 
Special population 
 
Hepatic impairment 
No dosage adjustment is required for patients with mild to moderate hepatic impairment. In patients 
with severe hepatic impairment, the data available are insufficient to establish recommendations. In 
these patients dosing should be managed cautiously. However, the maximum daily dose of 30 mg 
should be used with caution in patients with severe hepatic impairment (see section 5.2). 
 
Renal impairment 
No dosage adjustment is required in patients with renal impairment. 
 
Elderly 
The safety and efficacy of ABILIFY in the treatment of schizophrenia or manic episodes in Bipolar I 
Disorder in patients aged 65 years and older has not been established. Owing to the greater sensitivity 
of this population, a lower starting dose should be considered when clinical factors warrant (see 
section 4.4). 
 
Gender 
No dosage adjustment is required for female patients as compared to male patients (see section 5.2). 
 
Smoking status 
According to the metabolic pathway of aripiprazole no dosage adjustment is required for smokers (see 
section 4.5). 
 
Dose adjustments due to interactions 
When concomitant administration of strong CYP3A4 or CYP2D6 inhibitors with aripiprazole occurs, 
the aripiprazole dose should be reduced. When the CYP3A4 or CYP2D6 inhibitor is withdrawn from 
the combination therapy, aripiprazole dose should then be increased (see section 4.5). 
When concomitant administration of strong CYP3A4 inducers with aripiprazole occurs, the 
aripiprazole dose should be increased. When the CYP3A4 inducer is withdrawn from the combination 
therapy, the aripiprazole dose should then be reduced to the recommended dose (see section 4.5). 
 
Method of administration 
 
ABILIFY is for oral use. 
 
Orodispersible tablets or oral solution may be used as an alternative to ABILIFY tablets for patients 
who have difficulty swallowing ABILIFY tablets (see section 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
During antipsychotic treatment, improvement in the patient's clinical condition may take several days 
to some weeks. Patients should be closely monitored throughout this period. 
 
Suicidality 
 
The occurrence of suicidal behaviour is inherent in psychotic illnesses and mood disorders and in 



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some cases has been reported early after initiation or switch of antipsychotic treatment, including 
treatment with aripiprazole (see section 4.8). Close supervision of high-risk patients should 
accompany antipsychotic treatment. 
 
Cardiovascular disorders 
 
Aripiprazole should be used with caution in patients with known cardiovascular disease (history of 
myocardial infarction or ischaemic heart disease, heart failure, or conduction abnormalities), 
cerebrovascular disease, conditions which would predispose patients to hypotension (dehydration, 
hypovolemia, and treatment with antihypertensive medicinal products) or hypertension, including 
accelerated or malignant. Cases of venous thromboembolism (VTE) have been reported with 
antipsychotic medicinal products. Since patients treated with antipsychotics often present with 
acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during 
treatment with aripiprazole and preventive measures undertaken. 
 
QT prolongation 
 
In clinical trials of aripiprazole, the incidence of QT prolongation was comparable to placebo. 
Aripiprazole should be used with caution in patients with a family history of QT prolongation (see 
section 4.8). 
 
Tardive dyskinesia 
 
In clinical trials of one year or less duration, there were uncommon reports of treatment emergent 
dyskinesia during treatment with aripiprazole. If signs and symptoms of tardive dyskinesia appear in a 
patient on aripiprazole, dose reduction or discontinuation should be considered (see section 4.8). These 
symptoms can temporally deteriorate or can even arise after discontinuation of treatment. 
 
Other extrapyramidal symptoms 
 
In paediatric clinical trials of aripiprazole akathisia and Parkinsonism were observed. If signs and 
symptoms of other EPS appear in a patient taking aripiprazole, dose reduction and close clinical 
monitoring should be considered. 
 
Neuroleptic Malignant Syndrome (NMS) 
 
NMS is a potentially fatal symptom complex associated with antipsychotics. In clinical trials, rare 
cases of NMS were reported during treatment with aripiprazole. Clinical manifestations of NMS are 
hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular 
pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may 
include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. 
However, elevated creatine phosphokinase and rhabdomyolysis, not necessarily in association with 
NMS, have also been reported. If a patient develops signs and symptoms indicative of NMS, or 
presents with unexplained high fever without additional clinical manifestations of NMS, all 
antipsychotics, including aripiprazole, must be discontinued. 
 
Seizure 
 
In clinical trials, uncommon cases of seizure were reported during treatment with aripiprazole. 
Therefore, aripiprazole should be used with caution in patients who have a history of seizure disorder 
or have conditions associated with seizures (see section 4.8). 
 
Elderly patients with dementia-related psychosis 
 
Increased mortality 
In three placebo-controlled trials (n = 938; mean age: 82.4 years; range: 56 to 99 years) of aripiprazole 
in elderly patients with psychosis associated with Alzheimer's disease, patients treated with 



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aripiprazole were at increased risk of death compared to placebo. The rate of death in aripiprazole-
treated patients was 3.5 % compared to 1.7 % in the placebo group. Although the causes of deaths 
were varied, most of the deaths appeared to be either cardiovascular (e.g. heart failure, sudden death) 
or infectious (e.g. pneumonia) in nature (see section 4.8). 
 
Cerebrovascular adverse reactions 
In the same trials, cerebrovascular adverse reactions (e.g. stroke, transient ischaemic attack), including 
fatalities, were reported in patients (mean age: 84 years; range: 78 to 88 years). Overall, 1.3 % of 
aripiprazole-treated patients reported cerebrovascular adverse reactions compared with 0.6 % of 
placebo-treated patients in these trials. This difference was not statistically significant. However, in 
one of these trials, a fixed-dose trial, there was a significant dose response relationship for 
cerebrovascular adverse reactions in patients treated with aripiprazole (see section 4.8). 
 
Aripiprazole is not indicated for the treatment of patients with dementia-related psychosis. 
 
Hyperglycaemia and diabetes mellitus 
 
Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or 
death, has been reported in patients treated with atypical antipsychotics, including aripiprazole. Risk 
factors that may predispose patients to severe complications include obesity and family history of 
diabetes. In clinical trials with aripiprazole, there were no significant differences in the incidence rates 
of hyperglycaemia-related adverse reactions (including diabetes) or in abnormal glycaemia laboratory 
values compared to placebo. Precise risk estimates for hyperglycaemia-related adverse reactions in 
patients treated with aripiprazole and with other atypical antipsychotics are not available to allow 
direct comparisons. Patients treated with any antipsychotics, including aripiprazole, should be 
observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and 
weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be 
monitored regularly for worsening of glucose control (see section 4.8). 
 
Hypersensitivity 
 
Hypersensitivity reactions, characterised by allergic symptoms, may occur with aripiprazole (see 
section 4.8). 
 
Weight gain 
 
Weight gain is commonly seen in schizophrenic and bipolar mania patients due to co-morbidities, use 
of antipsychotics known to cause weight gain, poorly managed life-style, and might lead to severe 
complications. Weight gain has been reported post-marketing among patients prescribed aripiprazole. 
When seen, it is usually in those with significant risk factors such as history of diabetes, thyroid 
disorder or pituitary adenoma. In clinical trials aripiprazole has not been shown to induce clinically 
relevant weight gain in adults (see section 5.1). In clinical trials of adolescent patients with bipolar 
mania, aripiprazole has been shown to be associated with weight gain after 4 weeks of treatment. 
Weight gain should be monitored in adolescent patients with bipolar mania. If weight gain is clinically 
significant, dose reduction should be considered (see section 4.8). 
 
Dysphagia 
 
Oesophageal dysmotility and aspiration have been associated with the use of antipsychotics, including 
aripiprazole. Aripiprazole should be used cautiously in patients at risk for aspiration pneumonia. 
 
Pathological gambling and other impulse control disorders 
 
Patients can experience increased urges, particularly for gambling, and the inability to control these 
urges while taking aripiprazole. Other urges, reported, include: increased sexual urges, compulsive 
shopping, binge or compulsive eating, and other impulsive and compulsive behaviours. It is important 
for prescribers to ask patients or their caregivers specifically about the development of new or 



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increased gambling urges, sexual urges, compulsive shopping, binge or compulsive eating, or other 
urges while being treated with aripiprazole. It should be noted that impulse-control symptoms can be 
associated with the underlying disorder; however, in some cases, urges were reported to have stopped 
when the dose was reduced or the medication was discontinued. Impulse control disorders may result 
in harm to the patient and others if not recognised. Consider dose reduction or stopping the medication 
if a patient develops such urges while taking aripiprazole (see section 4.8). 
 
Lactose 
 
ABILIFY tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total 
lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. 
 
Patients with attention deficit hyperactivity disorder (ADHD) comorbidity 
 
Despite the high comorbidity frequency of Bipolar I Disorder and ADHD, very limited safety data are 
available on concomitant use of aripiprazole and stimulants; therefore, extreme caution should be 
taken when these medicinal products are co-administered. 
 
Falls 
 
Aripiprazole may cause somnolence, postural hypotension, motor and sensory instability, which may 
lead to falls. Caution should be taken when treating patients at higher risk, and a lower starting dose 
should be considered (e.g., elderly or debilitated patients; see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Due to its α1-adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of 
certain antihypertensive medicinal products. 
 
Given the primary CNS effects of aripiprazole, caution should be used when aripiprazole is 
administered in combination with alcohol or other CNS medicinal products with overlapping adverse 
reactions such as sedation (see section 4.8). 
 
If aripiprazole is administered concomitantly with medicinal products known to cause QT 
prolongation or electrolyte imbalance, caution should be used. 
 
Potential for other medicinal products to affect aripiprazole 
 
A gastric acid blocker, the H2 antagonist famotidine, reduces aripiprazole rate of absorption but this 
effect is deemed not clinically relevant. Aripiprazole is metabolised by multiple pathways involving 
the CYP2D6 and CYP3A4 enzymes but not CYP1A enzymes. Thus, no dosage adjustment is required 
for smokers. 
 
Quinidine and other CYP2D6 inhibitors 
In a clinical trial in healthy subjects, a strong inhibitor of CYP2D6 (quinidine) increased aripiprazole 
AUC by 107 %, while Cmax was unchanged. The AUC and Cmax of dehydro-aripiprazole, the active 
metabolite, decreased by 32 % and 47 %, respectively. Aripiprazole dose should be reduced to 
approximately one-half of its prescribed dose when concomitant administration of aripiprazole with 
quinidine occurs. Other strong inhibitors of CYP2D6, such as fluoxetine and paroxetine, may be 
expected to have similar effects and similar dose reductions should therefore be applied. 
 
Ketoconazole and other CYP3A4 inhibitors 
In a clinical trial in healthy subjects, a strong inhibitor of CYP3A4 (ketoconazole) increased 
aripiprazole AUC and Cmax by 63 % and 37 %, respectively. The AUC and Cmax of dehydro-
aripiprazole increased by 77 % and 43 %, respectively. In CYP2D6 poor metabolisers, concomitant 
use of strong inhibitors of CYP3A4 may result in higher plasma concentrations of aripiprazole 
compared to that in CYP2D6 extensive metabolizers. When considering concomitant administration of 



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ketoconazole or other strong CYP3A4 inhibitors with aripiprazole, potential benefits should outweigh 
the potential risks to the patient. When concomitant administration of ketoconazole with aripiprazole 
occurs, aripiprazole dose should be reduced to approximately one-half of its prescribed dose. Other 
strong inhibitors of CYP3A4, such as itraconazole and HIV protease inhibitors may be expected to 
have similar effects and similar dose reductions should therefore be applied (see section 4.2). Upon 
discontinuation of the CYP2D6 or CYP3A4 inhibitor, the dosage of aripiprazole should be increased 
to the level prior to the initiation of the concomitant therapy. When weak inhibitors of CYP3A4 (e.g. 
diltiazem) or CYP2D6 (e.g. escitalopram) are used concomitantly with aripiprazole, modest increases 
in plasma aripiprazole concentrations may be expected. 
 
Carbamazepine and other CYP3A4 inducers 
Following concomitant administration of carbamazepine, a strong inducer of CYP3A4, and oral 
aripiprazole to patients with schizophrenia or schizoaffective disorder, the geometric means of Cmax 
and AUC for aripiprazole were 68 % and 73 % lower, respectively, compared to when aripiprazole 
(30 mg) was administered alone. Similarly, for dehydro-aripiprazole the geometric means of Cmax and 
AUC after carbamazepine co-administration were 69 % and 71 % lower, respectively, than those 
following treatment with aripiprazole alone. Aripiprazole dose should be doubled when concomitant 
administration of aripiprazole occurs with carbamazepine. Concomitant administration of aripiprazole 
and other inducers of CYP3A4 (such as rifampicin, rifabutin, phenytoin, phenobarbital, primidone, 
efavirenz, nevirapine and St. John's Wort) may be expected to have similar effects and similar dose 
increases should therefore be applied. Upon discontinuation of strong CYP3A4 inducers, the dosage of 
aripiprazole should be reduced to the recommended dose. 
 
Valproate and lithium 
When either valproate or lithium was administered concomitantly with aripiprazole, there was no 
clinically significant change in aripiprazole concentrations and therefore no dose adjustment is 
necessary when either valproate or lithium is administered with aripiprazole. 
 
Potential for aripiprazole to affect other medicinal products 
 
In clinical studies, 10 mg/day to 30 mg/day doses of aripiprazole had no significant effect on the 
metabolism of substrates of CYP2D6 (dextromethorphan/3-methoxymorphinan ratio), 
CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP3A4 (dextromethorphan). Additionally, 
aripiprazole and dehydro-aripiprazole did not show potential for altering CYP1A2-mediated 
metabolism in vitro. Thus, aripiprazole is unlikely to cause clinically important medicinal product 
interactions mediated by these enzymes. 
 
When aripiprazole was administered concomitantly with either valproate, lithium or lamotrigine, there 
was no clinically important change in valproate, lithium or lamotrigine concentrations. 
 
Serotonin syndrome 
Cases of serotonin syndrome have been reported in patients taking aripiprazole, and possible signs and 
symptoms for this condition can occur especially in cases of concomitant use with other serotonergic 
medicinal products, such as selective serotonin reuptake inhibitor/selective serotonin noradrenaline 
reuptake inhibitor (SSRI/SNRI), or with medicinal products that are known to increase aripiprazole 
concentrations (see section 4.8). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate and well-controlled trials of aripiprazole in pregnant women. Congenital 
anomalies have been reported; however, causal relationship with aripiprazole could not be established. 
Animal studies could not exclude potential developmental toxicity (see section 5.3). Patients must be 
advised to notify their physician if they become pregnant or intend to become pregnant during 
treatment with aripiprazole. Due to insufficient safety information in humans and concerns raised by 
animal reproductive studies, this medicinal product should not be used in pregnancy unless the 



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expected benefit clearly justifies the potential risk to the foetus. 
 
Newborn infants exposed to antipsychotics (including aripiprazole) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborn 
infants should be monitored carefully (see section 4.8). 
 
Breast-feeding 
 
Aripiprazole/metabolites are excreted in human milk. A decision must be made whether to discontinue 
breast-feeding or to discontinue/abstain from aripiprazole therapy taking into account the benefit of 
breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
Aripiprazole did not impair fertility based on data from reproductive toxicity studies. 
 
4.7 Effects on ability to drive and use machines 
 
Aripiprazole has minor to moderate influence on the ability to drive and use machines due to potential 
nervous system and visual effects, such as sedation, somnolence, syncope, vision blurred, diplopia (see 
section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most commonly reported adverse reactions in placebo-controlled trials were akathisia and nausea 
each occurring in more than 3 % of patients treated with oral aripiprazole. 
 
Tabulated list of adverse reactions 
 
The incidences of the Adverse Drug Reactions (ADRs) associated with aripiprazole therapy are 
tabulated below. The table is based on adverse events reported during clinical trials and/or post-
marketing use. 
 
All ADRs are listed by system organ class and frequency; very common (≥ 1/10), common (≥ 1/100 to 
< 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and 
not known (cannot be estimated from the available data). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness. 
 
The frequency of adverse reactions reported during post-marketing use cannot be determined as they 
are derived from spontaneous reports. Consequently, the frequency of these adverse events is qualified 
as "not known". 
 
 Common Uncommon Not known 
Blood and 
lymphatic system 
disorders 

  Leukopenia 
Neutropenia 
Thrombocytopenia 

Immune system 
disorders 

  Allergic reaction (e.g. 
anaphylactic reaction, 
angioedema including swollen 
tongue, tongue oedema, face 
oedema, pruritus allergic, or 
urticaria) 

Endocrine  Hyperprolactinaemia Diabetic hyperosmolar coma 



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 Common Uncommon Not known 
disorders Diabetic ketoacidosis 
Metabolism and 
nutrition disorders 

Diabetes mellitus Hyperglycaemia Hyponatremia 
Anorexia 

Psychiatric 
disorders 

Insomnia 
Anxiety 
Restlessness 

Depression 
Hypersexuality 

Suicide attempt, suicidal ideation 
and completed suicide (see 
section 4.4) 
Pathological gambling 
Impulse-control disorder 
Binge eating 
Compulsive shopping 
Poriomania 
Aggression 
Agitation 
Nervousness  

Nervous system 
disorders 

Akathisia 
Extrapyramidal 
disorder 
Tremor 
Headache 
Sedation 
Somnolence 
Dizziness 

Tardive dyskinesia 
Dystonia 
Restless legs 
syndrome 
 

Neuroleptic Malignant Syndrome 
Grand mal convulsion 
Serotonin syndrome 
Speech disorder 

Eye disorders Vision blurred Diplopia 
Photophobia 

Oculogyric crisis 

Cardiac disorders  Tachycardia 
 

Sudden death unexplained 
Torsades de pointes 
Ventricular arrhythmia 
Cardiac arrest 
Bradycardia 

Vascular disorders  Orthostatic 
hypotension 

Venous thromboembolism 
(including pulmonary embolism 
and deep vein thrombosis) 
Hypertension 
Syncope 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Hiccups Aspiration pneumonia 
Laryngospasm 
Oropharyngeal spasm 
 

Gastrointestinal 
disorders 

Constipation 
Dyspepsia 
Nausea 
Salivary 
hypersecretion 
Vomiting 

  Pancreatitis 
Dysphagia 
Diarrhoea 
Abdominal discomfort 
Stomach discomfort 
 

Hepatobiliary 
disorders 

  Hepatic failure 
Hepatitis 
Jaundice 

Skin and 
subcutaneous tissue 
disorders 

  Rash 
Photosensitivity reaction 
Alopecia 
Hyperhidrosis 
Drug Reaction with Eosinophilia 
and Systemic Symptoms 
(DRESS) 

Musculoskeletal 
and connective 

  Rhabdomyolysis 
Myalgia 



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 Common Uncommon Not known 
tissue disorders Stiffness 
Renal and urinary 
disorders 

  Urinary incontinence 
Urinary retention 

Pregnancy, 
puerperium and 
perinatal conditions 

  Drug withdrawal syndrome 
neonatal (see section 4.6) 

Reproductive 
system and breast 
disorders 

  Priapism 

General disorders 
and administration 
site conditions 

Fatigue 
 

 Temperature regulation disorder 
(e.g. hypothermia, pyrexia) 
Chest pain 
Peripheral oedema 

Investigations   Weight decreased 
Weight gain 
Alanine Aminotransferase 
increased 
Aspartate Aminotransferase 
increased 
Gamma-glutamyltransferase 
increased 
Alkaline phosphatase increased 
QT prolonged 
Blood glucose increased 
Glycosylated haemoglobin 
increased 
Blood glucose fluctuation 
Creatine phosphokinase increased 

 
Description of selected adverse reactions 
 
Adults 
 
Extrapyramidal symptoms (EPS) 
Schizophrenia: in a long-term 52-week controlled trial, aripiprazole-treated patients had an overall-
lower incidence (25.8 %) of EPS including Parkinsonism, akathisia, dystonia and dyskinesia compared 
with those treated with haloperidol (57.3 %). In a long-term 26-week placebo-controlled trial, the 
incidence of EPS was 19 % for aripiprazole-treated patients and 13.1 % for placebo-treated patients. In 
another long-term 26-week controlled trial, the incidence of EPS was 14.8 % for aripiprazole-treated 
patients and 15.1 % for olanzapine-treated patients. 
 
Manic episodes in Bipolar I Disorder: in a 12-week controlled trial, the incidence of EPS was 23.5 % 
for aripiprazole-treated patients and 53.3 % for haloperidol-treated patients. In another 12-week trial, 
the incidence of EPS was 26.6 % for patients treated with aripiprazole and 17.6 % for those treated 
with lithium. In the long-term 26-week maintenance phase of a placebo-controlled trial, the incidence 
of EPS was 18.2 % for aripiprazole-treated patients and 15.7 % for placebo-treated patients. 
 
Akathisia 
In placebo-controlled trials, the incidence of akathisia in bipolar patients was 12.1 % with aripiprazole 
and 3.2 % with placebo. In schizophrenia 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 muscle groups, may occur in 
susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of 
the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty 



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breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur 
more frequently and with greater severity with high potency and at higher doses of first generation 
antipsychotic medicinal products. An elevated risk of acute dystonia is observed in males and younger 
age groups. 
 
Prolactin 
In clinical trials for the approved indications and post-marketing, both increase and decrease in serum 
prolactin as compared to baseline was observed with aripiprazole (section 5.1). 
 
Laboratory parameters 
Comparisons between aripiprazole and placebo in the proportions of patients experiencing potentially 
clinically significant changes in routine laboratory and lipid parameters (see section 5.1) revealed no 
medically important differences. Elevations of CPK (Creatine Phosphokinase), generally transient and 
asymptomatic, were observed in 3.5 % of aripiprazole treated patients as compared to 2.0 % of 
patients who received placebo. 
 
Paediatric population 
 
Schizophrenia in adolescents aged 15 years and older 
In a short-term placebo-controlled clinical trial involving 302 adolescents (13 to 17 years) with 
schizophrenia, the frequency and type of adverse reactions were similar to those in adults except for 
the following reactions that were reported more frequently in adolescents receiving aripiprazole than 
in adults receiving aripiprazole (and more frequently than placebo): 
Somnolence/sedation and extrapyramidal disorder were reported very commonly (≥ 1/10), and dry 
mouth, increased appetite, and orthostatic hypotension were reported commonly (≥ 1/100, < 1/10). 
The safety profile in a 26-week open-label extension trial was similar to that observed in the short-
term, placebo-controlled trial. 
The safety profile of a long-term, double-blind, placebo-controlled trial was also similar except for the 
following reactions that were reported more frequently than paediatric patients taking placebo: weight 
decreased, blood insulin increased, arrhythmia, and leukopenia were reported commonly (≥ 1/100, 
< 1/10). 
 
In the pooled adolescent schizophrenia population (13 to 17 years) with exposure up to 2 years, 
incidence of low serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) was 29.5 % 
and 48.3 %, respectively. In the adolescent (13 to 17 years) schizophrenia population with aripiprazole 
exposure of 5 mg to 30 mg up to 72 months, incidence of low serum prolactin levels in females 
(< 3 ng/mL) and males (< 2 ng/mL) was 25.6 % and 45.0 %, respectively. 
In two long-term trials with adolescent (13 to 17 years) schizophrenia and bipolar patients treated with 
aripiprazole, incidence of low serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) 
was 37.0 % and 59.4 %, respectively. 
 
Manic episodes in Bipolar I Disorder in adolescents aged 13 years and older 
The frequency and type of adverse reactions in adolescents with Bipolar I Disorder were similar to 
those in adults except for the following reactions: very commonly (≥ 1/10) somnolence (23.0 %), 
extrapyramidal disorder (18.4 %), akathisia (16.0 %), and fatigue (11.8 %); and commonly (≥ 1/100, 
< 1/10) abdominal pain upper, heart rate increased, weight increased, increased appetite, muscle 
twitching, and dyskinesia. 
 
The following adverse reactions had a possible dose response relationship; extrapyramidal disorder 
(incidences were 10 mg, 9.1 %; 30 mg, 28.8 %; placebo, 1.7 %); and akathisia (incidences were 
10 mg, 12.1 %; 30 mg, 20.3 %; placebo, 1.7 %). 
 
Mean changes in body weight in adolescents with Bipolar I Disorder at 12 and 30 weeks for 
aripiprazole were 2.4 kg and 5.8 kg, and for placebo 0.2 kg and 2.3 kg, respectively. 
 
In the paediatric population somnolence and fatigue were observed more frequently in patients with 
bipolar disorder compared to patients with schizophrenia. 



 13 

 
In the paediatric bipolar population (10 to 17 years) with exposure up to 30 weeks, incidence of low 
serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) was 28.0 % and 53.3 %, 
respectively. 
 
Pathological gambling and other impulse control disorders 
Pathological gambling, hypersexuality, compulsive shopping and binge or compulsive eating can 
occur in patients treated with aripiprazole (see section 4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Signs and symptoms 
 
In clinical trials and post-marketing experience, accidental or intentional acute overdose of 
aripiprazole alone was identified in adult patients with reported estimated doses up to 1,260 mg with 
no fatalities. The potentially medically important signs and symptoms observed included lethargy, 
increased blood pressure, somnolence, tachycardia, nausea, vomiting and diarrhoea. In addition, 
reports of accidental overdose with aripiprazole alone (up to 195 mg) in children have been received 
with no fatalities. The potentially medically serious signs and symptoms reported included 
somnolence, transient loss of consciousness and extrapyramidal symptoms. 
 
Management of overdose 
 
Management of overdose should concentrate on supportive therapy, maintaining an adequate airway, 
oxygenation and ventilation, and management of symptoms. The possibility of multiple medicinal 
product involvement should be considered. Therefore cardiovascular monitoring should be started 
immediately and should include continuous electrocardiographic monitoring to detect possible 
arrhythmias. Following any confirmed or suspected overdose with aripiprazole, close medical 
supervision and monitoring should continue until the patient recovers. 
 
Activated charcoal (50 g), administered one hour after aripiprazole, decreased aripiprazole Cmax by 
about 41 % and AUC by about 51 %, suggesting that charcoal may be effective in the treatment of 
overdose. 
 
Haemodialysis 
 
Although there is no information on the effect of haemodialysis in treating an overdose with 
aripiprazole, haemodialysis is unlikely to be useful in overdose management since aripiprazole is 
highly bound to plasma proteins. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Psycholeptics, other antipsychotics, ATC code: N05AX12 
 
Mechanism of action 
 
It has been proposed that aripiprazole’s efficacy in schizophrenia and Bipolar I Disorder is mediated 
through a combination of partial agonism at dopamine D2 and serotonin 5-HT1A receptors and 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 14 

antagonism of serotonin 5-HT2A receptors. Aripiprazole exhibited antagonist properties in animal 
models of dopaminergic hyperactivity and agonist properties in animal models of dopaminergic 
hypoactivity. Aripiprazole exhibited high binding affinity in vitro for dopamine D2 and D3, serotonin 
5-HT1A and 5-HT2A receptors and moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, 
alpha-1 adrenergic and histamine H1 receptors. Aripiprazole also exhibited moderate binding affinity 
for the serotonin reuptake site and no appreciable affinity for muscarinic receptors. Interaction with 
receptors other than dopamine and serotonin subtypes may explain some of the other clinical effects of 
aripiprazole. 
 
Aripiprazole doses ranging from 0.5 mg to 30 mg administered once a day to healthy subjects for 
2 weeks produced a dose-dependent reduction in the binding of 11C-raclopride, a D2/D3 receptor 
ligand, to the caudate and putamen detected by positron emission tomography. 
 
Clinical efficacy and safety 
 
Adults 
 
Schizophrenia 
In three short-term (4 to 6 weeks) placebo-controlled trials involving 1,228 schizophrenic adult 
patients, presenting with positive or negative symptoms, aripiprazole was associated with statistically 
significantly greater improvements in psychotic symptoms compared to placebo. 
 
Aripiprazole is effective in maintaining the clinical improvement during continuation therapy in adult 
patients who have shown an initial treatment response. In a haloperidol-controlled trial, the proportion 
of responder patients maintaining response to medicinal product at 52-weeks was similar in both 
groups (aripiprazole 77 % and haloperidol 73 %). The overall completion rate was significantly higher 
for patients on aripiprazole (43 %) than for haloperidol (30 %). Actual scores in rating scales used as 
secondary endpoints, including PANSS and the Montgomery-Åsberg Depression Rating Scale 
(MADRS) showed a significant improvement over haloperidol. 
 
In a 26-week, placebo-controlled trial in adult stabilised patients with chronic schizophrenia, 
aripiprazole had significantly greater reduction in relapse rate, 34 % in aripiprazole group and 57 % in 
placebo. 
 
Weight gain 
In clinical trials aripiprazole has not been shown to induce clinically relevant weight gain. In a 
26-week, olanzapine-controlled, double-blind, multi-national study of schizophrenia which included 
314 adult patients and where the primary endpoint was weight gain, significantly less patients had at 
least 7 % weight gain over baseline (i.e. a gain of at least 5.6 kg for a mean baseline weight of 
~80.5 kg) on aripiprazole (n = 18, or 13 % of evaluable patients), compared to olanzapine (n = 45, or 
33 % of evaluable patients). 
 
Lipid parameters 
In a pooled analysis on lipid parameters from placebo controlled clinical trials in adults, aripiprazole 
has not been shown to induce clinically relevant alterations in levels of total cholesterol, triglycerides, 
High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL). 
 
Prolactin 
Prolactin levels were evaluated in all trials of all doses of aripiprazole (n = 28,242). The incidence of 
hyperprolactinaemia or increased serum prolactin in patients treated with aripiprazole (0.3 %) was 
similar to that of placebo (0.2 %). For patients receiving aripiprazole, the median time to onset was 
42 days and median duration was 34 days. 
 
The incidence of hypoprolactinaemia or decreased serum prolactin in patients treated with aripiprazole 
was 0.4 %, compared with 0.02 % for patients treated with placebo. For patients receiving 
aripiprazole, the median time to onset was 30 days and median duration was 194 days. 
 



 15 

Manic episodes in Bipolar I Disorder 
In two 3-week, flexible-dose, placebo-controlled monotherapy trials involving patients with a manic or 
mixed episode of Bipolar I Disorder, aripiprazole demonstrated superior efficacy to placebo in 
reduction of manic symptoms over 3 weeks. These trials included patients with or without psychotic 
features and with or without a rapid-cycling course. 
 
In one 3-week, fixed-dose, placebo-controlled monotherapy trial involving patients with a manic or 
mixed episode of Bipolar I Disorder, aripiprazole failed to demonstrate superior efficacy to placebo. 
 
In two 12-week, placebo- and active-controlled monotherapy trials in patients with a manic or mixed 
episode of Bipolar I Disorder, with or without psychotic features, aripiprazole demonstrated superior 
efficacy to placebo at week 3 and a maintenance of effect comparable to lithium or haloperidol at 
week 12. Aripiprazole also demonstrated a comparable proportion of patients in symptomatic 
remission from mania as lithium or haloperidol at week 12. 
 
In a 6-week, placebo-controlled trial involving patients with a manic or mixed episode of Bipolar I 
Disorder, with or without psychotic features, who were partially non-responsive to lithium or 
valproate monotherapy for 2 weeks at therapeutic serum levels, the addition of aripiprazole as 
adjunctive therapy resulted in superior efficacy in reduction of manic symptoms than lithium or 
valproate monotherapy. 
 
In a 26-week, placebo-controlled trial, followed by a 74-week extension, in manic patients who 
achieved remission on aripiprazole during a stabilization phase prior to randomisation, aripiprazole 
demonstrated superiority over placebo in preventing bipolar recurrence, primarily in preventing 
recurrence into mania but failed to demonstrate superiority over placebo in preventing recurrence into 
depression. 
 
In a 52-week, placebo-controlled trial, in patients with a current manic or mixed episode of Bipolar I 
Disorder who achieved sustained remission (Young Mania Rating Scale [YMRS] and MADRS with 
total scores ≤ 12) on aripiprazole (10 mg/day to 30 mg/day) adjunctive to lithium or valproate for 
12 consecutive weeks, adjunctive aripiprazole demonstrated superiority over placebo with a 46 % 
decreased risk (hazard ratio of 0.54) in preventing bipolar recurrence and a 65 % decreased risk 
(hazard ratio of 0.35) in preventing recurrence into mania over adjunctive placebo but failed to 
demonstrate superiority over placebo in preventing recurrence into depression. Adjunctive aripiprazole 
demonstrated superiority over placebo on the secondary outcome measure in Clinical Global 
Impression - Bipolar version (CGI-BP) Severity of Illness (SOI; mania) scores. In this trial, patients 
were assigned by investigators with either open-label lithium or valproate monotherapy to determine 
partial non-response. Patients were stabilised for at least 12 consecutive weeks with the combination 
of aripiprazole and the same mood stabilizer. Stabilized patients were then randomised to continue the 
same mood stabilizer with double-blind aripiprazole or placebo. Four mood stabilizer subgroups were 
assessed in the randomised phase: aripiprazole + lithium; aripiprazole + valproate; placebo + lithium; 
placebo + valproate. The Kaplan-Meier rates for recurrence to any mood episode for the adjunctive 
treatment arm were 16 % in aripiprazole + lithium and 18 % in aripiprazole + valproate compared to 
45 % in placebo + lithium and 19 % in placebo + valproate. 
 
Paediatric population 
 
Schizophrenia in adolescents 
In a 6-week placebo-controlled trial involving 302 schizophrenic adolescent patients (13 to 17 years), 
presenting with positive or negative symptoms, aripiprazole was associated with statistically 
significantly greater improvements in psychotic symptoms compared to placebo. In a sub-analysis of 
the adolescent patients between the ages of 15 to 17 years, representing 74 % of the total enrolled 
population, maintenance of effect was observed over the 26-week open-label extension trial. 
 
In a 60- to 89-week, randomised, double-blind, placebo-controlled trial in adolescent subjects 
(n = 146; ages 13 to 17 years) with schizophrenia, there was a statistically significant difference in the 
rate of relapse of psychotic symptoms between the aripiprazole (19.39 %) and placebo (37.50 %) 



 16 

groups. The point estimate of the hazard ratio (HR) was 0.461 (95 % confidence interval, 0.242 to 
0.879) in the full population. In sub-group analyses the point estimate of the HR was 0.495 for 
subjects 13 to 14 years of age compared to 0.454 for subjects 15 to 17 years of age. However, the 
estimation of the HR for the younger (13 to 14 years) group was not precise, reflecting the smaller 
number of subjects in that group (aripiprazole, n = 29; placebo, n = 12), and the confidence interval for 
this estimation (ranging from 0.151 to 1.628) did not allow conclusions to be drawn on the presence of 
a treatment effect. In contrast the 95 % confidence interval for the HR in the older subgroup 
(aripiprazole, n = 69; placebo, n = 36) was 0.242 to 0.879 and hence a treatment effect could be 
concluded in the older patients. 
 
Manic episodes in Bipolar I Disorder in children and adolescents 
Aripiprazole was studied in a 30-week placebo-controlled trial involving 296 children and adolescents 
(10 to 17 years), who met DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders) 
for Bipolar I Disorder with manic or mixed episodes with or without psychotic features and had a 
YMRS score ≥ 20 at baseline. Among the patients included in the primary efficacy analysis, 
139 patients had a current co-morbid diagnosis of ADHD. 
 
Aripiprazole was superior to placebo in change from baseline at week 4 and at week 12 on the Y-MRS 
total score. In a post-hoc analysis, the improvement over placebo was more pronounced in the patients 
with associated co-morbidity of ADHD compared to the group without ADHD, where there was no 
difference from placebo. Recurrence prevention was not established. 
 
The most common treatment-emergent adverse events among patients receiving 30 mg were 
extrapyramidal disorder (28.3 %), somnolence (27.3 %), headache (23.2 %), and nausea (14.1 %). 
Mean weight gain in the 30 weeks treatment-interval was 2.9 kg as compared to 0.98 kg in patients 
treated with placebo. 
 
Irritability associated with autistic disorder in paediatric patients (see section 4.2) 
Aripiprazole was studied in patients aged 6 to 17 years in two 8-week, placebo-controlled trials [one 
flexible-dose (2 mg/day to 15 mg/day) and one fixed-dose (5 mg/day, 10 mg/day, or 15 mg/day)] and 
in one 52-week open-label trial. Dosing in these trials was initiated at 2 mg/day, increased to 5 mg/day 
after one week, and increased by 5 mg/day in weekly increments to the target dose. Over 75 % of 
patients were less than 13 years of age. Aripiprazole demonstrated statistically superior efficacy 
compared to placebo on the Aberrant Behaviour Checklist Irritability subscale. However, the clinical 
relevance of this finding has not been established. The safety profile included weight gain and changes 
in prolactin levels. The duration of the long-term safety study was limited to 52 weeks. In the pooled 
trials, the incidence of low serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) in 
aripiprazole-treated patients was 27/46 (58.7 %) and 258/298 (86.6 %), respectively. In the placebo-
controlled trials, the mean weight gain was 0.4 kg for placebo and 1.6 kg for aripiprazole. 
 
Aripiprazole was also studied in a placebo-controlled, long-term maintenance trial. After a 13 to 
26-week stabilisation on aripiprazole (2 mg/day to 15 mg/day) patients with a stable response were 
either maintained on aripiprazole or substituted to placebo for further 16 weeks. Kaplan-Meier relapse 
rates at week 16 were 35 % for aripiprazole and 52 % for placebo; the hazard ratio for relapse within 
16 weeks (aripiprazole/placebo) was 0.57 (non-statistically significant difference). The mean weight 
gain over the stabilisation phase (up to 26 weeks) on aripiprazole was 3.2 kg, and a further mean 
increase of 2.2 kg for aripiprazole as compared to 0.6 kg for placebo was observed in the second phase 
(16 weeks) of the trial. Extrapyramidal symptoms were mainly reported during the stabilisation phase 
in 17 % of patients, with tremor accounting for 6.5 %. 
 
Tics associated with Tourette’s disorder in paediatric patients (see section 4.2) 
The efficacy of aripiprazole was studied in paediatric subjects with Tourette’s disorder (aripiprazole: 
n = 99, placebo: n = 44) in a randomised, double-blind, placebo-controlled, 8 week study using a fixed 
dose weight-based treatment group design over the dose range of 5 mg/day to 20 mg/day and a starting 
dose of 2 mg. Patients were 7 to 17 years of age and presented an average score of 30 on Total Tic 
Score on the Yale Global Tic Severity Scale (TTS-YGTSS) at baseline. Aripiprazole showed an 
improvement on TTS-YGTSS change from baseline to week 8 of 13.35, for the low dose group (5 mg 



 17 

or 10 mg) and 16.94 for the high dose group (10 mg or 20 mg) as compared with an improvement of 
7.09 in the placebo group. 
 
The efficacy of aripiprazole in paediatric subjects with Tourette’s syndrome (aripiprazole: n = 32, 
placebo: n = 29) was also evaluated over a flexible dose range of 2 mg/day to 20 mg/day and a starting 
dose of 2 mg, in a 10 week, randomised, double blind, placebo-controlled study conducted in South-
Korea. Patients were 6 to 18 years and presented an average score of 29 on TTS-YGTSS at baseline. 
Aripiprazole group showed an improvement of 14.97 on TTS-YGTSS change from baseline to 
week 10 as compared with an improvement of 9.62 in the placebo group. 
 
In both of these short-term trials, the clinical relevance of the efficacy findings has not been 
established, considering the magnitude of treatment effect compared to the large placebo effect and the 
unclear effects regarding psycho-social functioning. No long-term data are available with regard to the 
efficacy and the safety of aripiprazole in this fluctuating disorder. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
ABILIFY in one or more subsets of the paediatric population in the treatment of schizophrenia and in 
the treatment of bipolar affective disorder (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Aripiprazole is well absorbed, with peak plasma concentrations occurring within 3 to 5 hours after 
dosing. Aripiprazole undergoes minimal pre-systemic metabolism. The absolute oral bioavailability of 
the tablet formulation is 87 %. There is no effect of a high fat meal on the pharmacokinetics of 
aripiprazole. 
 
Distribution 
 
Aripiprazole is widely distributed throughout the body with an apparent volume of distribution of 
4.9 L/kg, indicating extensive extravascular distribution. At therapeutic concentrations, aripiprazole 
and dehydro-aripiprazole are greater than 99 % bound to serum proteins, binding primarily to albumin. 
 
Biotransformation 
 
Aripiprazole is extensively metabolised by the liver primarily by three biotransformation pathways: 
dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 
enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is 
catalysed by CYP3A4. Aripiprazole is the predominant medicinal product moiety in systemic 
circulation. At steady state, dehydro-aripiprazole, the active metabolite, represents about 40 % of 
aripiprazole AUC in plasma. 
 
Elimination 
 
The mean elimination half-lives for aripiprazole are approximately 75 hours in extensive metabolisers 
of CYP2D6 and approximately 146 hours in poor metabolisers of CYP2D6. 
 
The total body clearance of aripiprazole is 0.7 mL/min/kg, which is primarily hepatic. 
 
Following a single oral dose of [14C]-labelled aripiprazole, approximately 27 % of the administered 
radioactivity was recovered in the urine and approximately 60 % in the faeces. Less than 1 % of 
unchanged aripiprazole was excreted in the urine and approximately 18 % was recovered unchanged 
in the faeces. 
 
Paediatric population 
 



 18 

The pharmacokinetics of aripiprazole and dehydro-aripiprazole in paediatric patients 10 to 17 years of 
age were similar to those in adults after correcting for the differences in body weights. 
 
Pharmacokinetics in special patient groups 
 
Elderly 
There are no differences in the pharmacokinetics of aripiprazole between healthy elderly and younger 
adult subjects, nor is there any detectable effect of age in a population pharmacokinetic analysis in 
schizophrenic patients. 
 
Gender 
There are no differences in the pharmacokinetics of aripiprazole between healthy male and female 
subjects nor is there any detectable effect of gender in a population pharmacokinetic analysis in 
schizophrenic patients. 
 
Smoking 
Population pharmacokinetic evaluation has revealed no evidence of clinically significant effects from 
smoking on the pharmacokinetics of aripiprazole. 
 
Race 
Population pharmacokinetic evaluation showed no evidence of race-related differences on the 
pharmacokinetics of aripiprazole. 
 
Renal impairment 
The pharmacokinetic characteristics of aripiprazole and dehydro-aripiprazole were found to be similar 
in patients with severe renal disease compared to young healthy subjects. 
 
Hepatic impairment 
A single-dose study in subjects with varying degrees of liver cirrhosis (Child-Pugh Classes A, B, 
and C) did not reveal a significant effect of hepatic impairment on the pharmacokinetics of 
aripiprazole and dehydro-aripiprazole, but the study included only 3 patients with Class C liver 
cirrhosis, which is insufficient to draw conclusions on their metabolic capacity. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction 
and development. 
 
Toxicologically significant effects were observed only at doses or exposures that were sufficiently in 
excess of the maximum human dose or exposure, indicating that these effects were limited or of no 
relevance to clinical use. These included: dose-dependent adrenocortical toxicity (lipofuscin pigment 
accumulation and/or parenchymal cell loss) in rats after 104 weeks at 20 mg/kg/day to 60 mg/kg/day 
(3 to 10 times the mean steady-state AUC at the maximum recommended human dose) and increased 
adrenocortical carcinomas and combined adrenocortical adenomas/carcinomas in female rats at 
60 mg/kg/day (10 times the mean steady-state AUC at the maximum recommended human dose). The 
highest nontumorigenic exposure in female rats was 7 times the human exposure at the recommended 
dose. 
 
An additional finding was cholelithiasis as a consequence of precipitation of sulphate conjugates of 
hydroxy metabolites of aripiprazole in the bile of monkeys after repeated oral dosing at 25 mg/kg/day 
to 125 mg/kg/day (1 to 3 times the mean steady-state AUC at the maximum recommended clinical 
dose or 16 to 81 times the maximum recommended human dose based on mg/m2). However, the 
concentrations of the sulphate conjugates of hydroxy aripiprazole in human bile at the highest dose 
proposed, 30 mg per day, were no more than 6 % of the bile concentrations found in the monkeys in 
the 39-week study and are well below (6 %) their limits of in vitro solubility. 
 



 19 

In repeat-dose studies in juvenile rats and dogs, the toxicity profile of aripiprazole was comparable to 
that observed in adult animals, and there was no evidence of neurotoxicity or adverse reactions on 
development. 
 
Based on results of a full range of standard genotoxicity tests, aripiprazole was considered non-
genotoxic. Aripiprazole did not impair fertility in reproductive toxicity studies. Developmental 
toxicity, including dose-dependent delayed foetal ossification and possible teratogenic effects, were 
observed in rats at doses resulting in subtherapeutic exposures (based on AUC) and in rabbits at doses 
resulting in exposures 3 and 11 times the mean steady-state AUC at the maximum recommended 
clinical dose. Maternal toxicity occurred at doses similar to those eliciting developmental toxicity. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Lactose monohydrate 
Maize starch 
Microcrystalline cellulose 
Hydroxypropyl cellulose 
Magnesium stearate 
 
Tablet coat 
 
ABILIFY 5 mg tablets 
Indigo carmine aluminium lake (E 132) 
 
ABILIFY 10 mg tablets 
Red iron oxide (E 172) 
 
ABILIFY 15 mg tablets 
Yellow iron oxide (E 172) 
 
ABILIFY 30 mg tablets 
Red iron oxide (E 172) 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from moisture. 
 
6.5 Nature and contents of container 
 
Aluminium perforated unit dose blisters in cartons of 14 × 1, 28 × 1, 49 × 1, 56 × 1, 98 × 1 tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 



 20 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
ABILIFY 5 mg tablets 
EU/1/04/276/001 (5 mg, 14 × 1 tablets) 
EU/1/04/276/002 (5 mg, 28 × 1 tablets) 
EU/1/04/276/003 (5 mg, 49 × 1 tablets) 
EU/1/04/276/004 (5 mg, 56 × 1 tablets) 
EU/1/04/276/005 (5 mg, 98 × 1 tablets) 
 
ABILIFY 10 mg tablets 
EU/1/04/276/006 (10 mg, 14 × 1 tablets) 
EU/1/04/276/007 (10 mg, 28 × 1 tablets) 
EU/1/04/276/008 (10 mg, 49 × 1 tablets) 
EU/1/04/276/009 (10 mg, 56 × 1 tablets) 
EU/1/04/276/010 (10 mg, 98 × 1 tablets) 
 
ABILIFY 15 mg tablets 
EU/1/04/276/011 (15 mg, 14 × 1 tablets) 
EU/1/04/276/012 (15 mg, 28 × 1 tablets) 
EU/1/04/276/013 (15 mg, 49 × 1 tablets) 
EU/1/04/276/014 (15 mg, 56 × 1 tablets) 
EU/1/04/276/015 (15 mg, 98 × 1 tablets) 
 
ABILIFY 30 mg tablets 
EU/1/04/276/016 (30 mg, 14 × 1 tablets) 
EU/1/04/276/017 (30 mg, 28 × 1 tablets) 
EU/1/04/276/018 (30 mg, 49 × 1 tablets) 
EU/1/04/276/019 (30 mg, 56 × 1 tablets) 
EU/1/04/276/020 (30 mg, 98 × 1 tablets) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 04 June 2004 
Date of latest renewal: 04 June 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


 21 

1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 10 mg orodispersible tablets 
ABILIFY 15 mg orodispersible tablets 
ABILIFY 30 mg orodispersible tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
ABILIFY 10 mg orodispersible tablets 
Each orodispersible tablet contains 10 mg of aripiprazole. 
Excipient with known effect 
2 mg aspartame (E 951) and 0.075 mg lactose per orodispersible tablet 
 
ABILIFY 15 mg orodispersible tablets 
Each orodispersible tablet contains 15 mg of aripiprazole. 
Excipient with known effect 
3 mg aspartame (E 951) and 0.1125 mg lactose per orodispersible tablet 
 
ABILIFY 30 mg orodispersible tablets 
Each orodispersible tablet contains 30 mg of aripiprazole. 
Excipient with known effect 
6 mg aspartame (E 951) and 0.225 mg lactose per orodispersible tablet 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Orodispersible tablet 
 
ABILIFY 10 mg orodispersible tablets 
10 mg: Round and pink, marked with "A" over "640" on one side and "10" on the other. 
 
ABILIFY 15 mg orodispersible tablets 
15 mg: Round and yellow, marked with "A" over "641" on one side and "15" on the other. 
 
ABILIFY 30 mg orodispersible tablets 
30 mg: Round and pink, marked with "A" over "643" on one side and "30" on the other. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
ABILIFY is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years 
and older. 
 
ABILIFY is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder 
and for the prevention of a new manic episode in adults who experienced predominantly manic 
episodes and whose manic episodes responded to aripiprazole treatment (see section 5.1). 
 
ABILIFY is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in 
Bipolar I Disorder in adolescents aged 13 years and older (see section 5.1). 
 
4.2 Posology and method of administration 
 



 22 

Posology 
 
Adults 
 
Schizophrenia: the recommended starting dose for ABILIFY is 10 mg/day or 15 mg/day with a 
maintenance dose of 15 mg/day administered on a once-a-day schedule without regard to meals. 
ABILIFY is effective in a dose range of 10 mg/day to 30 mg/day. Enhanced efficacy at doses higher 
than a daily dose of 15 mg has not been demonstrated although individual patients may benefit from a 
higher dose. The maximum daily dose should not exceed 30 mg. 
 
Manic episodes in Bipolar I Disorder: the recommended starting dose for ABILIFY is 15 mg 
administered on a once-a-day schedule without regard to meals as monotherapy or combination 
therapy (see section 5.1). Some patients may benefit from a higher dose. The maximum daily dose 
should not exceed 30 mg. 
 
Recurrence prevention of manic episodes in Bipolar I Disorder: for preventing recurrence of manic 
episodes in patients, who have been receiving aripiprazole as monotherapy or combination therapy, 
continue therapy at the same dose. Adjustments of daily dosage, including dose reduction should be 
considered on the basis of clinical status. 
 
Paediatric population 
 
Schizophrenia in adolescents aged 15 years and older: the recommended dose for ABILIFY is 
10 mg/day administered on a once-a-day schedule without regard to meals. Treatment should be 
initiated at 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 dose of 10 mg. When appropriate, subsequent dose increases 
should be administered in 5 mg increments without exceeding the maximum daily dose of 30 mg (see 
section 5.1). ABILIFY is effective in a dose range of 10 mg/day to 30 mg/day. Enhanced efficacy at 
doses higher than a daily dose of 10 mg has not been demonstrated although individual patients may 
benefit from a higher dose. 
ABILIFY is not recommended for use in patients with schizophrenia below 15 years of age due to 
insufficient data on safety and efficacy (see sections 4.8 and 5.1). 
 
Manic episodes in Bipolar I Disorder in adolescents aged 13 years and older: the recommended dose 
for ABILIFY is 10 mg/day administered on a once-a-day schedule without regard to meals. Treatment 
should be initiated at 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 dose of 10 mg. The treatment duration should be the 
minimum necessary for symptom control and must not exceed 12 weeks. Enhanced efficacy at doses 
higher than a daily dose of 10 mg has not been demonstrated, and a daily dose of 30 mg is associated 
with a substantially higher incidence of significant adverse reactions including EPS related events, 
somnolence, fatigue and weight gain (see section 4.8). Doses higher than 10 mg/day should therefore 
only be used in exceptional cases and with close clinical monitoring (see sections 4.4, 4.8 and 5.1). 
Younger patients are at increased risk of experiencing adverse events associated with aripiprazole. 
Therefore, ABILIFY is not recommended for use in patients below 13 years of age (see sections 4.8 
and 5.1). 
 
Irritability associated with autistic disorder: the safety and efficacy of ABILIFY in children and 
adolescents aged below 18 years have not yet been established. Currently available data are described 
in section 5.1 but no recommendation on a posology can be made. 
 
Tics associated with Tourette’s disorder: the safety and efficacy of ABILIFY in children and 
adolescents 6 to 18 years of age have not yet been established. Currently available data are described 
in section 5.1 but no recommendation on a posology can be made. 
 
Special populations 
 
Hepatic impairment 



 23 

No dosage adjustment is required for patients with mild to moderate hepatic impairment. In patients 
with severe hepatic impairment, the data available are insufficient to establish recommendations. In 
these patients dosing should be managed cautiously. However, the maximum daily dose of 30 mg 
should be used with caution in patients with severe hepatic impairment (see section 5.2). 
 
Renal impairment 
No dosage adjustment is required in patients with renal impairment. 
 
Elderly 
The safety and efficacy of ABILIFY in the treatment of schizophrenia or manic episodes in Bipolar I 
Disorder in patients aged 65 years and older has not been established. Owing to the greater sensitivity 
of this population, a lower starting dose should be considered when clinical factors warrant (see 
section 4.4). 
 
Gender 
No dosage adjustment is required for female patients as compared to male patients (see section 5.2). 
 
Smoking status 
According to the metabolic pathway of aripiprazole no dosage adjustment is required for smokers (see 
section 4.5). 
 
Dose adjustments due to interactions 
When concomitant administration of strong CYP3A4 or CYP2D6 inhibitors with aripiprazole occurs, 
the aripiprazole dose should be reduced. When the CYP3A4 or CYP2D6 inhibitor is withdrawn from 
the combination therapy, aripiprazole dose should then be increased (see section 4.5). 
When concomitant administration of strong CYP3A4 inducers with aripiprazole occurs, the 
aripiprazole dose should be increased. When the CYP3A4 inducer is withdrawn from the combination 
therapy, the aripiprazole dose should then be reduced to the recommended dose (see section 4.5). 
 
Method of administration 
 
ABILIFY is for oral use. 
 
The orodispersible tablet should be placed in the mouth on the tongue, where it will rapidly disperse in 
saliva. It can be taken with or without liquid. Removal of the intact orodispersible tablet from the 
mouth is difficult. Since the orodispersible tablet is fragile, it should be taken immediately on opening 
the blister. Alternatively, disperse the tablet in water and drink the resulting suspension. 
 
Orodispersible tablets or oral solution may be used as an alternative to ABILIFY tablets for patients 
who have difficulty swallowing ABILIFY tablets (see section 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
During antipsychotic treatment, improvement in the patient's clinical condition may take several days 
to some weeks. Patients should be closely monitored throughout this period. 
 
Suicidality 
 
The occurrence of suicidal behaviour is inherent in psychotic illnesses and mood disorders and in 
some cases has been reported early after initiation or switch of antipsychotic treatment, including 
treatment with aripiprazole (see section 4.8). Close supervision of high-risk patients should 
accompany antipsychotic treatment. 
 



 24 

Cardiovascular disorders 
 
Aripiprazole should be used with caution in patients with known cardiovascular disease (history of 
myocardial infarction or ischaemic heart disease, heart failure, or conduction abnormalities), 
cerebrovascular disease, conditions which would predispose patients to hypotension (dehydration, 
hypovolemia, and treatment with antihypertensive medicinal products) or hypertension, including 
accelerated or malignant. Cases of venous thromboembolism (VTE) have been reported with 
antipsychotic medicinal products. Since patients treated with antipsychotics often present with 
acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during 
treatment with aripiprazole and preventive measures undertaken. 
 
QT prolongation 
 
In clinical trials of aripiprazole, the incidence of QT prolongation was comparable to placebo. 
Aripiprazole should be used with caution in patients with a family history of QT prolongation (see 
section 4.8). 
 
Tardive dyskinesia 
 
In clinical trials of one year or less duration, there were uncommon reports of treatment emergent 
dyskinesia during treatment with aripiprazole. If signs and symptoms of tardive dyskinesia appear in a 
patient on aripiprazole, dose reduction or discontinuation should be considered (see section 4.8). These 
symptoms can temporally deteriorate or can even arise after discontinuation of treatment. 
 
Other extrapyramidal symptoms 
 
In paediatric clinical trials of aripiprazole akathisia and Parkinsonism were observed. If signs and 
symptoms of other EPS appear in a patient taking aripiprazole, dose reduction and close clinical 
monitoring should be considered. 
 
Neuroleptic Malignant Syndrome (NMS) 
 
NMS is a potentially fatal symptom complex associated with antipsychotics. In clinical trials, rare 
cases of NMS were reported during treatment with aripiprazole. Clinical manifestations of NMS are 
hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular 
pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may 
include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. 
However, elevated creatine phosphokinase and rhabdomyolysis, not necessarily in association with 
NMS, have also been reported. If a patient develops signs and symptoms indicative of NMS, or 
presents with unexplained high fever without additional clinical manifestations of NMS, all 
antipsychotics, including aripiprazole, must be discontinued. 
 
Seizure 
 
In clinical trials, uncommon cases of seizure were reported during treatment with aripiprazole. 
Therefore, aripiprazole should be used with caution in patients who have a history of seizure disorder 
or have conditions associated with seizures (see section 4.8). 
 
Elderly patients with dementia-related psychosis 
 
Increased mortality 
In three placebo-controlled trials (n = 938; mean age: 82.4 years; range: 56 to 99 years) of aripiprazole 
in elderly patients with psychosis associated with Alzheimer's disease, patients treated with 
aripiprazole were at increased risk of death compared to placebo. The rate of death in aripiprazole-
treated patients was 3.5 % compared to 1.7 % in the placebo group. Although the causes of deaths 
were varied, most of the deaths appeared to be either cardiovascular (e.g. heart failure, sudden death) 
or infectious (e.g. pneumonia) in nature (see section 4.8). 



 25 

 
Cerebrovascular adverse reactions 
In the same trials, cerebrovascular adverse reactions (e.g. stroke, transient ischaemic attack), including 
fatalities, were reported in patients (mean age: 84 years; range: 78 to 88 years). Overall, 1.3 % of 
aripiprazole-treated patients reported cerebrovascular adverse reactions compared with 0.6 % of 
placebo-treated patients in these trials. This difference was not statistically significant. However, in 
one of these trials, a fixed-dose trial, there was a significant dose response relationship for 
cerebrovascular adverse reactions in patients treated with aripiprazole (see section 4.8). 
 
Aripiprazole is not indicated for the treatment of patients with dementia-related psychosis. 
 
Hyperglycaemia and diabetes mellitus 
 
Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or 
death, has been reported in patients treated with atypical antipsychotics, including aripiprazole. Risk 
factors that may predispose patients to severe complications include obesity and family history of 
diabetes. In clinical trials with aripiprazole, there were no significant differences in the incidence rates 
of hyperglycaemia-related adverse reactions (including diabetes) or in abnormal glycaemia laboratory 
values compared to placebo. Precise risk estimates for hyperglycaemia-related adverse reactions in 
patients treated with aripiprazole and with other atypical antipsychotics are not available to allow 
direct comparisons. Patients treated with any antipsychotics, including aripiprazole, should be 
observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and 
weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be 
monitored regularly for worsening of glucose control (see section 4.8). 
 
Hypersensitivity 
 
Hypersensitivity reactions, characterised by allergic symptoms, may occur with aripiprazole (see 
section 4.8). 
 
Weight gain 
 
Weight gain is commonly seen in schizophrenic and bipolar mania patients due to co-morbidities, use 
of antipsychotics known to cause weight gain, poorly managed life-style, and might lead to severe 
complications. Weight gain has been reported post-marketing among patients prescribed aripiprazole. 
When seen, it is usually in those with significant risk factors such as history of diabetes, thyroid 
disorder or pituitary adenoma. In clinical trials aripiprazole has not been shown to induce clinically 
relevant weight gain in adults (see section 5.1). In clinical trials of adolescent patients with bipolar 
mania, aripiprazole has been shown to be associated with weight gain after 4 weeks of treatment. 
Weight gain should be monitored in adolescent patients with bipolar mania. If weight gain is clinically 
significant, dose reduction should be considered (see section 4.8). 
 
Dysphagia 
 
Oesophageal dysmotility and aspiration have been associated with the use of antipsychotics, including 
aripiprazole. Aripiprazole should be used cautiously in patients at risk for aspiration pneumonia. 
 
Pathological gambling and other impulse control disorders 
 
Patients can experience increased urges, particularly for gambling, and the inability to control these 
urges while taking aripiprazole. Other urges, reported, include: increased sexual urges, compulsive 
shopping, binge or compulsive eating, and other impulsive and compulsive behaviours. It is important 
for prescribers to ask patients or their caregivers specifically about the development of new or 
increased gambling urges, sexual urges, compulsive shopping, binge or compulsive eating, or other 
urges while being treated with aripiprazole. It should be noted that impulse-control symptoms can be 
associated with the underlying disorder; however, in some cases, urges were reported to have stopped 
when the dose was reduced or the medication was discontinued. Impulse control disorders may result 



 26 

in harm to the patient and others if not recognised. Consider dose reduction or stopping the medication 
if a patient develops such urges while taking aripiprazole (see section 4.8). 
 
Aspartame 
 
ABILIFY orodispersible tablets contain aspartame. Aspartame is a source of phenylalanine. It may be 
harmful for people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds 
up because the body cannot remove it properly. 
 
Lactose 
 
ABILIFY orodispersible tablets contain lactose. Patients with rare hereditary problems of galactose 
intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal 
product. 
 
Sodium 
 
ABILIFY orodispersible tablets contain sodium. This medicinal product contains less than 1 mmol 
sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’. 
 
Patients with attention deficit hyperactivity disorder (ADHD) comorbidity 
 
Despite the high comorbidity frequency of Bipolar I Disorder and ADHD, very limited safety data are 
available on concomitant use of aripiprazole and stimulants; therefore, extreme caution should be 
taken when these medicinal products are co-administered. 
 
Falls 
 
Aripiprazole may cause somnolence, postural hypotension, motor and sensory instability, which may 
lead to falls. Caution should be taken when treating patients at higher risk, and a lower starting dose 
should be considered (e.g., elderly or debilitated patients; see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Due to its α1-adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of 
certain antihypertensive medicinal products. 
 
Given the primary CNS effects of aripiprazole, caution should be used when aripiprazole is 
administered in combination with alcohol or other CNS medicinal products with overlapping adverse 
reactions such as sedation (see section 4.8). 
 
If aripiprazole is administered concomitantly with medicinal products known to cause QT 
prolongation or electrolyte imbalance, caution should be used. 
 
Potential for other medicinal products to affect aripiprazole 
 
A gastric acid blocker, the H2 antagonist famotidine, reduces aripiprazole rate of absorption but this 
effect is deemed not clinically relevant. Aripiprazole is metabolised by multiple pathways involving 
the CYP2D6 and CYP3A4 enzymes but not CYP1A enzymes. Thus, no dosage adjustment is required 
for smokers. 
 
Quinidine and other CYP2D6 inhibitors 
In a clinical trial in healthy subjects, a strong inhibitor of CYP2D6 (quinidine) increased aripiprazole 
AUC by 107 %, while Cmax was unchanged. The AUC and Cmax of dehydro-aripiprazole, the active 
metabolite, decreased by 32 % and 47 %, respectively. Aripiprazole dose should be reduced to 
approximately one-half of its prescribed dose when concomitant administration of aripiprazole with 
quinidine occurs. Other strong inhibitors of CYP2D6, such as fluoxetine and paroxetine, may be 



 27 

expected to have similar effects and similar dose reductions should therefore be applied. 
 
Ketoconazole and other CYP3A4 inhibitors 
In a clinical trial in healthy subjects, a strong inhibitor of CYP3A4 (ketoconazole) increased 
aripiprazole AUC and Cmax by 63 % and 37 %, respectively. The AUC and Cmax of dehydro-
aripiprazole increased by 77 % and 43 %, respectively. In CYP2D6 poor metabolisers, concomitant 
use of strong inhibitors of CYP3A4 may result in higher plasma concentrations of aripiprazole 
compared to that in CYP2D6 extensive metabolizers. When considering concomitant administration of 
ketoconazole or other strong CYP3A4 inhibitors with aripiprazole, potential benefits should outweigh 
the potential risks to the patient. When concomitant administration of ketoconazole with aripiprazole 
occurs, aripiprazole dose should be reduced to approximately one-half of its prescribed dose. Other 
strong inhibitors of CYP3A4, such as itraconazole and HIV protease inhibitors may be expected to 
have similar effects and similar dose reductions should therefore be applied (see section 4.2). Upon 
discontinuation of the CYP2D6 or CYP3A4 inhibitor, the dosage of aripiprazole should be increased 
to the level prior to the initiation of the concomitant therapy. When weak inhibitors of CYP3A4 (e.g. 
diltiazem) or CYP2D6 (e.g. escitalopram) are used concomitantly with aripiprazole, modest increases 
in plasma aripiprazole concentrations may be expected. 
 
Carbamazepine and other CYP3A4 inducers 
Following concomitant administration of carbamazepine, a strong inducer of CYP3A4, and oral 
aripiprazole to patients with schizophrenia or schizoaffective disorder, the geometric means of Cmax 
and AUC for aripiprazole were 68 % and 73 % lower, respectively, compared to when aripiprazole 
(30 mg) was administered alone. Similarly, for dehydro-aripiprazole the geometric means of Cmax and 
AUC after carbamazepine co-administration were 69 % and 71 % lower, respectively, than those 
following treatment with aripiprazole alone. Aripiprazole dose should be doubled when concomitant 
administration of aripiprazole occurs with carbamazepine. Concomitant administration of aripiprazole 
and other inducers of CYP3A4 (such as rifampicin, rifabutin, phenytoin, phenobarbital, primidone, 
efavirenz, nevirapine and St. John's Wort) may be expected to have similar effects and similar dose 
increases should therefore be applied. Upon discontinuation of strong CYP3A4 inducers, the dosage of 
aripiprazole should be reduced to the recommended dose. 
 
Valproate and lithium 
When either valproate or lithium was administered concomitantly with aripiprazole, there was no 
clinically significant change in aripiprazole concentrations and therefore no dose adjustment is 
necessary when either valproate or lithium is administered with aripiprazole. 
 
Potential for aripiprazole to affect other medicinal products 
 
In clinical studies, 10 mg/day to 30 mg/day doses of aripiprazole had no significant effect on the 
metabolism of substrates of CYP2D6 (dextromethorphan/3-methoxymorphinan ratio), 
CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP3A4 (dextromethorphan). Additionally, 
aripiprazole and dehydro-aripiprazole did not show potential for altering CYP1A2-mediated 
metabolism in vitro. Thus, aripiprazole is unlikely to cause clinically important medicinal product 
interactions mediated by these enzymes. 
 
When aripiprazole was administered concomitantly with either valproate, lithium or lamotrigine, there 
was no clinically important change in valproate, lithium or lamotrigine concentrations. 
 
Serotonin syndrome 
Cases of serotonin syndrome have been reported in patients taking aripiprazole, and possible signs and 
symptoms for this condition can occur especially in cases of concomitant use with other serotonergic 
medicinal products, such as selective serotonin reuptake inhibitor/selective serotonin noradrenaline 
reuptake inhibitor (SSRI/SNRI), or with medicinal products that are known to increase aripiprazole 
concentrations (see section 4.8). 
 
4.6 Fertility, pregnancy and lactation 
 



 28 

Pregnancy 
 
There are no adequate and well-controlled trials of aripiprazole in pregnant women. Congenital 
anomalies have been reported; however, causal relationship with aripiprazole could not be established. 
Animal studies could not exclude potential developmental toxicity (see section 5.3). Patients must be 
advised to notify their physician if they become pregnant or intend to become pregnant during 
treatment with aripiprazole. Due to insufficient safety information in humans and concerns raised by 
animal reproductive studies, this medicinal product should not be used in pregnancy unless the 
expected benefit clearly justifies the potential risk to the foetus. 
 
Newborn infants exposed to antipsychotics (including aripiprazole) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborn 
infants should be monitored carefully (see section 4.8). 
 
Breast-feeding 
 
Aripiprazole/metabolites are excreted in human milk. A decision must be made whether to discontinue 
breast-feeding or to discontinue/abstain from aripiprazole therapy taking into account the benefit of 
breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
Aripiprazole did not impair fertility based on data from reproductive toxicity studies. 
 
 
4.7 Effects on ability to drive and use machines 
 
Aripiprazole has minor to moderate influence on the ability to drive and use machines due to potential 
nervous system and visual effects, such as sedation, somnolence, syncope, vision blurred, diplopia (see 
section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most commonly reported adverse reactions in placebo-controlled trials were akathisia and nausea 
each occurring in more than 3 % of patients treated with oral aripiprazole. 
 
Tabulated list of adverse reactions 
 
The incidences of the Adverse Drug Reactions (ADRs) associated with aripiprazole therapy are 
tabulated below. The table is based on adverse events reported during clinical trials and/or post-
marketing use. 
 
All ADRs are listed by system organ class and frequency; very common (≥ 1/10), common (≥ 1/100 to 
< 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and 
not known (cannot be estimated from the available data). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness. 
 
The frequency of adverse reactions reported during post-marketing use cannot be determined as they 
are derived from spontaneous reports. Consequently, the frequency of these adverse events is qualified 
as "not known". 
 
 Common Uncommon Not known 

 



 29 

 Common Uncommon Not known 
 

Blood and 
lymphatic system 
disorders 

  Leukopenia 
Neutropenia 
Thrombocytopenia 

Immune system 
disorders 

  Allergic reaction (e.g. 
anaphylactic reaction, 
angioedema including swollen 
tongue, tongue oedema, face 
oedema, pruritus allergic, or 
urticaria) 

Endocrine 
disorders 

 Hyperprolactinaemia 
 

Diabetic hyperosmolar coma 
Diabetic ketoacidosis 
 

Metabolism and 
nutrition disorders 

Diabetes mellitus Hyperglycaemia Hyponatremia 
Anorexia 

Psychiatric 
disorders 

Insomnia 
Anxiety 
Restlessness 

Depression 
Hypersexuality 

Suicide attempt, suicidal ideation 
and completed suicide (see 
section 4.4) 
Pathological gambling 
Impulse-control disorder 
Binge eating 
Compulsive shopping 
Poriomania 
Aggression 
Agitation 
Nervousness  

Nervous system 
disorders 

Akathisia 
Extrapyramidal 
disorder 
Tremor 
Headache 
Sedation 
Somnolence 
Dizziness 

Tardive dyskinesia 
Dystonia 
Restless legs 
syndrome 
 

Neuroleptic Malignant Syndrome 
Grand mal convulsion 
Serotonin syndrome 
Speech disorder 
 

Eye disorders Vision blurred Diplopia 
Photophobia 

Oculogyric crisis 

Cardiac disorders  Tachycardia 
 

Sudden death unexplained  
Torsades de pointes 
Ventricular arrhythmia 
Cardiac arrest 
Bradycardia 

Vascular disorders  Orthostatic 
hypotension 
 

Venous thromboembolism 
(including pulmonary embolism 
and deep vein thrombosis) 
Hypertension 
Syncope 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Hiccups Aspiration pneumonia 
Laryngospasm 
Oropharyngeal spasm 
 

Gastrointestinal 
disorders 

Constipation 
Dyspepsia 
Nausea 
Salivary 
hypersecretion 
Vomiting 

 Pancreatitis 
Dysphagia 
Diarrhoea 
Abdominal discomfort 
Stomach discomfort 
 



 30 

 Common Uncommon Not known 
 

Hepatobiliary 
disorders 

  Hepatic failure 
Hepatitis 
Jaundice 

Skin and 
subcutaneous tissue 
disorders 

  Rash 
Photosensitivity reaction 
Alopecia 
Hyperhidrosis 
Drug Reaction with Eosinophilia 
and Systemic Symptoms 
(DRESS) 

Musculoskeletal 
and connective 
tissue disorders 

  Rhabdomyolysis 
Myalgia 
Stiffness 

Renal and urinary 
disorders 

  Urinary incontinence 
Urinary retention 

Pregnancy, 
puerperium and 
perinatal conditions 

  Drug withdrawal syndrome 
neonatal (see section 4.6) 

Reproductive 
system and breast 
disorders 

  Priapism 

General disorders 
and administration 
site conditions 

Fatigue 
 

 Temperature regulation disorder 
(e.g. hypothermia, pyrexia) 
Chest pain 
Peripheral oedema 

Investigations   Weight decreased 
Weight gain 
Alanine Aminotransferase 
increased 
Aspartate Aminotransferase 
increased 
Gamma-glutamyltransferase 
increased 
Alkaline phosphatase increased 
QT prolonged 
Blood glucose increased 
Glycosylated haemoglobin 
increased 
Blood glucose fluctuation 
Creatine phosphokinase increased 

 
Description of selected adverse reactions 
 
Adults 
 
Extrapyramidal symptoms (EPS) 
Schizophrenia: in a long-term 52-week controlled trial, aripiprazole-treated patients had an overall-
lower incidence (25.8 %) of EPS including Parkinsonism, akathisia, dystonia and dyskinesia compared 
with those treated with haloperidol (57.3 %). In a long-term 26-week placebo-controlled trial, the 
incidence of EPS was 19 % for aripiprazole-treated patients and 13.1 % for placebo-treated patients. In 
another long-term 26-week controlled trial, the incidence of EPS was 14.8 % for aripiprazole-treated 
patients and 15.1 % for olanzapine-treated patients. 
 
Manic episodes in Bipolar I Disorder: in a 12-week controlled trial, the incidence of EPS was 23.5 % 
for aripiprazole-treated patients and 53.3 % for haloperidol-treated patients. In another 12-week trial, 



 31 

the incidence of EPS was 26.6 % for patients treated with aripiprazole and 17.6 % for those treated 
with lithium. In the long-term 26-week maintenance phase of a placebo-controlled trial, the incidence 
of EPS was 18.2 % for aripiprazole-treated patients and 15.7 % for placebo-treated patients. 
 
Akathisia 
In placebo-controlled trials, the incidence of akathisia in bipolar patients was 12.1 % with aripiprazole 
and 3.2 % with placebo. In schizophrenia 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 muscle groups, may occur in 
susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of 
the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty 
breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur 
more frequently and with greater severity with high potency and at higher doses of first generation 
antipsychotic medicinal products. An elevated risk of acute dystonia is observed in males and younger 
age groups. 
 
Prolactin 
In clinical trials for the approved indications and post-marketing, both increase and decrease in serum 
prolactin as compared to baseline was observed with aripiprazole (section 5.1). 
 
Laboratory parameters 
Comparisons between aripiprazole and placebo in the proportions of patients experiencing potentially 
clinically significant changes in routine laboratory and lipid parameters (see section 5.1) revealed no 
medically important differences. Elevations of CPK (Creatine Phosphokinase), generally transient and 
asymptomatic, were observed in 3.5 % of aripiprazole treated patients as compared to 2.0 % of 
patients who received placebo. 
 
Paediatric population 
 
Schizophrenia in adolescents aged 15 years and older 
In a short-term placebo-controlled clinical trial involving 302 adolescents (13 to 17 years) with 
schizophrenia, the frequency and type of adverse reactions were similar to those in adults except for 
the following reactions that were reported more frequently in adolescents receiving aripiprazole than 
in adults receiving aripiprazole (and more frequently than placebo): 
Somnolence/sedation and extrapyramidal disorder were reported very commonly (≥ 1/10), and dry 
mouth, increased appetite, and orthostatic hypotension were reported commonly (≥ 1/100, < 1/10). 
The safety profile in a 26-week open-label extension trial was similar to that observed in the short-
term, placebo-controlled trial. 
The safety profile of a long-term, double-blind, placebo-controlled trial was also similar except for the 
following reactions that were reported more frequently than paediatric patients taking placebo: weight 
decreased, blood insulin increased, arrhythmia, and leukopenia were reported commonly (≥ 1/100, 
< 1/10). 
 
In the pooled adolescent schizophrenia population (13 to 17 years) with exposure up to 2 years, 
incidence of low serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) was 29.5 % 
and 48.3 %, respectively. In the adolescent (13 to 17 years) schizophrenia population with aripiprazole 
exposure of 5 mg to 30 mg up to 72 months, incidence of low serum prolactin levels in females 
(< 3 ng/mL) and males (< 2 ng/mL) was 25.6 % and 45.0 %, respectively. 
In two long-term trials with adolescent (13 to 17 years) schizophrenia and bipolar patients treated with 
aripiprazole, incidence of low serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) 
was 37.0 % and 59.4 %, respectively. 
 
Manic episodes in Bipolar I Disorder in adolescents aged 13 years and older 
The frequency and type of adverse reactions in adolescents with Bipolar I Disorder were similar to 
those in adults except for the following reactions: very commonly (≥ 1/10) somnolence (23.0 %), 



 32 

extrapyramidal disorder (18.4 %), akathisia (16.0 %), and fatigue (11.8 %); and commonly (≥ 1/100, 
< 1/10) abdominal pain upper, heart rate increased, weight increased, increased appetite, muscle 
twitching, and dyskinesia. 
 
The following adverse reactions had a possible dose response relationship; extrapyramidal disorder 
(incidences were 10 mg, 9.1 %; 30 mg, 28.8 %; placebo, 1.7 %); and akathisia (incidences were 
10 mg, 12.1 %; 30 mg, 20.3 %; placebo, 1.7 %). 
 
Mean changes in body weight in adolescents with Bipolar I Disorder at 12 and 30 weeks for 
aripiprazole were 2.4 kg and 5.8 kg, and for placebo 0.2 kg and 2.3 kg, respectively. 
 
In the paediatric population somnolence and fatigue were observed more frequently in patients with 
bipolar disorder compared to patients with schizophrenia. 
 
In the paediatric bipolar population (10 to 17 years) with exposure up to 30 weeks, incidence of low 
serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) was 28.0 % and 53.3 %, 
respectively. 
 
Pathological gambling and other impulse control disorders 
Pathological gambling, hypersexuality, compulsive shopping and binge or compulsive eating can 
occur in patients treated with aripiprazole (see section 4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Signs and symptoms 
 
In clinical trials and post-marketing experience, accidental or intentional acute overdose of 
aripiprazole alone was identified in adult patients with reported estimated doses up to 1,260 mg with 
no fatalities. The potentially medically important signs and symptoms observed included lethargy, 
increased blood pressure, somnolence, tachycardia, nausea, vomiting and diarrhoea. In addition, 
reports of accidental overdose with aripiprazole alone (up to 195 mg) in children have been received 
with no fatalities. The potentially medically serious signs and symptoms reported included 
somnolence, transient loss of consciousness and extrapyramidal symptoms. 
 
Management of overdose 
 
Management of overdose should concentrate on supportive therapy, maintaining an adequate airway, 
oxygenation and ventilation, and management of symptoms. The possibility of multiple medicinal 
product involvement should be considered. Therefore cardiovascular monitoring should be started 
immediately and should include continuous electrocardiographic monitoring to detect possible 
arrhythmias. Following any confirmed or suspected overdose with aripiprazole, close medical 
supervision and monitoring should continue until the patient recovers. 
 
Activated charcoal (50 g), administered one hour after aripiprazole, decreased aripiprazole Cmax by 
about 41 % and AUC by about 51 %, suggesting that charcoal may be effective in the treatment of 
overdose. 
 
Haemodialysis 
 
Although there is no information on the effect of haemodialysis in treating an overdose with 
aripiprazole, haemodialysis is unlikely to be useful in overdose management since aripiprazole is 

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 33 

highly bound to plasma proteins. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Psycholeptics, other antipsychotics, ATC code: N05AX12 
 
Mechanism of action 
 
It has been proposed that aripiprazole’s efficacy in schizophrenia and Bipolar I Disorder is mediated 
through a combination of partial agonism at dopamine D2 and serotonin 5-HT1A receptors and 
antagonism of serotonin 5-HT2A receptors. Aripiprazole exhibited antagonist properties in animal 
models of dopaminergic hyperactivity and agonist properties in animal models of dopaminergic 
hypoactivity. Aripiprazole exhibited high binding affinity in vitro for dopamine D2 and D3, serotonin 
5-HT1A and 5-HT2A receptors and moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, 
alpha-1 adrenergic and histamine H1 receptors. Aripiprazole also exhibited moderate binding affinity 
for the serotonin reuptake site and no appreciable affinity for muscarinic receptors. Interaction with 
receptors other than dopamine and serotonin subtypes may explain some of the other clinical effects of 
aripiprazole. 
 
Aripiprazole doses ranging from 0.5 mg to 30 mg administered once a day to healthy subjects for 
2 weeks produced a dose-dependent reduction in the binding of 11C-raclopride, a D2/D3 receptor 
ligand, to the caudate and putamen detected by positron emission tomography. 
 
Clinical efficacy and safety 
 
Adults 
 
Schizophrenia 
In three short-term (4 to 6 weeks) placebo-controlled trials involving 1,228 schizophrenic adult 
patients, presenting with positive or negative symptoms, aripiprazole was associated with statistically 
significantly greater improvements in psychotic symptoms compared to placebo. 
 
Aripiprazole is effective in maintaining the clinical improvement during continuation therapy in adult 
patients who have shown an initial treatment response. In a haloperidol-controlled trial, the proportion 
of responder patients maintaining response to medicinal product at 52-weeks was similar in both 
groups (aripiprazole 77 % and haloperidol 73 %). The overall completion rate was significantly higher 
for patients on aripiprazole (43 %) than for haloperidol (30 %). Actual scores in rating scales used as 
secondary endpoints, including PANSS and the Montgomery-Åsberg Depression Rating Scale 
(MADRS) showed a significant improvement over haloperidol. 
 
In a 26-week, placebo-controlled trial in adult stabilised patients with chronic schizophrenia, 
aripiprazole had significantly greater reduction in relapse rate, 34 % in aripiprazole group and 57 % in 
placebo. 
 
Weight gain 
In clinical trials aripiprazole has not been shown to induce clinically relevant weight gain. In a 
26-week, olanzapine-controlled, double-blind, multi-national study of schizophrenia which included 
314 adult patients and where the primary endpoint was weight gain, significantly less patients had at 
least 7 % weight gain over baseline (i.e. a gain of at least 5.6 kg for a mean baseline weight of 
~80.5 kg) on aripiprazole (n = 18, or 13 % of evaluable patients), compared to olanzapine (n = 45, or 
33 % of evaluable patients). 
 
Lipid parameters 
In a pooled analysis on lipid parameters from placebo controlled clinical trials in adults, aripiprazole 



 34 

has not been shown to induce clinically relevant alterations in levels of total cholesterol, triglycerides, 
High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL). 
 
Prolactin 
Prolactin levels were evaluated in all trials of all doses of aripiprazole (n = 28,242). The incidence of 
hyperprolactinaemia or increased serum prolactin in patients treated with aripiprazole (0.3 %) was 
similar to that of placebo (0.2 %). For patients receiving aripiprazole, the median time to onset was 
42 days and median duration was 34 days. 
 
The incidence of hypoprolactinaemia or decreased serum prolactin in patients treated with aripiprazole 
was 0.4 %, compared with 0.02 % for patients treated with placebo. For patients receiving 
aripiprazole, the median time to onset was 30 days and median duration was 194 days. 
 
Manic episodes in Bipolar I Disorder 
In two 3-week, flexible-dose, placebo-controlled monotherapy trials involving patients with a manic or 
mixed episode of Bipolar I Disorder, aripiprazole demonstrated superior efficacy to placebo in 
reduction of manic symptoms over 3 weeks. These trials included patients with or without psychotic 
features and with or without a rapid-cycling course. 
 
In one 3-week, fixed-dose, placebo-controlled monotherapy trial involving patients with a manic or 
mixed episode of Bipolar I Disorder, aripiprazole failed to demonstrate superior efficacy to placebo. 
 
In two 12-week, placebo- and active-controlled monotherapy trials in patients with a manic or mixed 
episode of Bipolar I Disorder, with or without psychotic features, aripiprazole demonstrated superior 
efficacy to placebo at week 3 and a maintenance of effect comparable to lithium or haloperidol at 
week 12. Aripiprazole also demonstrated a comparable proportion of patients in symptomatic 
remission from mania as lithium or haloperidol at week 12. 
 
In a 6-week, placebo-controlled trial involving patients with a manic or mixed episode of Bipolar I 
Disorder, with or without psychotic features, who were partially non-responsive to lithium or 
valproate monotherapy for 2 weeks at therapeutic serum levels, the addition of aripiprazole as 
adjunctive therapy resulted in superior efficacy in reduction of manic symptoms than lithium or 
valproate monotherapy. 
 
In a 26-week, placebo-controlled trial, followed by a 74-week extension, in manic patients who 
achieved remission on aripiprazole during a stabilization phase prior to randomisation, aripiprazole 
demonstrated superiority over placebo in preventing bipolar recurrence, primarily in preventing 
recurrence into mania but failed to demonstrate superiority over placebo in preventing recurrence into 
depression. 
 
In a 52-week, placebo-controlled trial, in patients with a current manic or mixed episode of Bipolar I 
Disorder who achieved sustained remission (Young Mania Rating Scale [YMRS] and MADRS with 
total scores ≤ 12) on aripiprazole (10 mg/day to 30 mg/day) adjunctive to lithium or valproate for 
12 consecutive weeks, adjunctive aripiprazole demonstrated superiority over placebo with a 46 % 
decreased risk (hazard ratio of 0.54) in preventing bipolar recurrence and a 65 % decreased risk 
(hazard ratio of 0.35) in preventing recurrence into mania over adjunctive placebo but failed to 
demonstrate superiority over placebo in preventing recurrence into depression. Adjunctive aripiprazole 
demonstrated superiority over placebo on the secondary outcome measure in Clinical Global 
Impression - Bipolar version (CGI-BP) Severity of Illness (SOI; mania) scores. In this trial, patients 
were assigned by investigators with either open-label lithium or valproate monotherapy to determine 
partial non-response. Patients were stabilised for at least 12 consecutive weeks with the combination 
of aripiprazole and the same mood stabilizer. Stabilized patients were then randomised to continue the 
same mood stabilizer with double-blind aripiprazole or placebo. Four mood stabilizer subgroups were 
assessed in the randomised phase: aripiprazole + lithium; aripiprazole + valproate; placebo + lithium; 
placebo + valproate. The Kaplan-Meier rates for recurrence to any mood episode for the adjunctive 
treatment arm were 16 % in aripiprazole + lithium and 18 % in aripiprazole + valproate compared to 
45 % in placebo + lithium and 19 % in placebo + valproate. 



 35 

 
Paediatric population 
 
Schizophrenia in adolescents 
In a 6-week placebo-controlled trial involving 302 schizophrenic adolescent patients (13 to 17 years), 
presenting with positive or negative symptoms, aripiprazole was associated with statistically 
significantly greater improvements in psychotic symptoms compared to placebo. In a sub-analysis of 
the adolescent patients between the ages of 15 to 17 years, representing 74 % of the total enrolled 
population, maintenance of effect was observed over the 26-week open-label extension trial. 
 
In a 60- to 89-week, randomised, double-blind, placebo-controlled trial in adolescent subjects 
(n = 146; ages 13 to 17 years) with schizophrenia, there was a statistically significant difference in the 
rate of relapse of psychotic symptoms between the aripiprazole (19.39 %) and placebo (37.50 %) 
groups. The point estimate of the hazard ratio (HR) was 0.461 (95 % confidence interval, 0.242 to 
0.879) in the full population. In subgroup analyses the point estimate of the HR was 0.495 for subjects 
13 to 14 years of age compared to 0.454 for subjects 15 to 17 years of age. However, the estimation of 
the HR for the younger (13 to 14 years) group was not precise, reflecting the smaller number of 
subjects in that group (aripiprazole, n = 29; placebo, n = 12), and the confidence interval for this 
estimation (ranging from 0.151 to 1.628) did not allow conclusions to be drawn on the presence of a 
treatment effect. In contrast the 95 % confidence interval for the HR in the older subgroup 
(aripiprazole, n = 69; placebo, n = 36) was 0.242 to 0.879 and hence a treatment effect could be 
concluded in the older patients. 
 
Manic episodes in Bipolar I Disorder in children and adolescents 
Aripiprazole was studied in a 30-week placebo-controlled trial involving 296 children and adolescents 
(10 to 17 years), who met DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders) 
for Bipolar I Disorder with manic or mixed episodes with or without psychotic features and had a 
YMRS score ≥ 20 at baseline. Among the patients included in the primary efficacy analysis, 
139 patients had a current co-morbid diagnosis of ADHD. 
 
Aripiprazole was superior to placebo in change from baseline at week 4 and at week 12 on the Y-MRS 
total score. In a post-hoc analysis, the improvement over placebo was more pronounced in the patients 
with associated co-morbidity of ADHD compared to the group without ADHD, where there was no 
difference from placebo. Recurrence prevention was not established. 
 
The most common treatment-emergent adverse events among patients receiving 30 mg were 
extrapyramidal disorder (28.3 %), somnolence (27.3 %), headache (23.2 %), and nausea (14.1 %). 
Mean weight gain in the 30 weeks treatment-interval was 2.9 kg as compared to 0.98 kg in patients 
treated with placebo. 
 
Irritability associated with autistic disorder in paediatric patients (see section 4.2) 
Aripiprazole was studied in patients aged 6 to 17 years in two 8-week, placebo-controlled trials [one 
flexible-dose (2 mg/day to 15 mg/day) and one fixed-dose (5 mg/day, 10 mg/day, or 15 mg/day)] and 
in one 52-week open-label trial. Dosing in these trials was initiated at 2 mg/day, increased to 5 mg/day 
after one week, and increased by 5 mg/day in weekly increments to the target dose. Over 75 % of 
patients were less than 13 years of age. Aripiprazole demonstrated statistically superior efficacy 
compared to placebo on the Aberrant Behaviour Checklist Irritability subscale. However, the clinical 
relevance of this finding has not been established. The safety profile included weight gain and changes 
in prolactin levels. The duration of the long-term safety study was limited to 52 weeks. In the pooled 
trials, the incidence of low serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) in 
aripiprazole-treated patients was 27/46 (58.7 %) and 258/298 (86.6 %), respectively. In the placebo-
controlled trials, the mean weight gain was 0.4 kg for placebo and 1.6 kg for aripiprazole. 
 
Aripiprazole was also studied in a placebo-controlled, long-term maintenance trial. After a 13 to 
26-week stabilisation on aripiprazole (2 mg/day to 15 mg/day) patients with a stable response were 
either maintained on aripiprazole or substituted to placebo for further 16 weeks. Kaplan-Meier relapse 
rates at week 16 were 35 % for aripiprazole and 52 % for placebo; the hazard ratio for relapse within 



 36 

16 weeks (aripiprazole/placebo) was 0.57 (non-statistically significant difference). The mean weight 
gain over the stabilisation phase (up to 26 weeks) on aripiprazole was 3.2 kg, and a further mean 
increase of 2.2 kg for aripiprazole as compared to 0.6 kg for placebo was observed in the second phase 
(16 weeks) of the trial. Extrapyramidal symptoms were mainly reported during the stabilisation phase 
in 17 % of patients, with tremor accounting for 6.5 %. 
 
Tics associated with Tourette’s disorder in paediatric patients (see section 4.2) 
The efficacy of aripiprazole was studied in paediatric subjects with Tourette’s disorder (aripiprazole: 
n = 99, placebo: n = 44) in a randomised, double-blind, placebo controlled, 8 week study using a fixed 
dose weight-based treatment group design over the dose range of 5 mg/day to 20 mg/day and a starting 
dose of 2 mg. Patients were 7 to 17 years of age and presented an average score of 30 on Total Tic 
Score on the Yale Global Tic Severity Scale (TTS-YGTSS) at baseline. Aripiprazole showed an 
improvement on TTS-YGTSS change from baseline to week 8 of 13.35, for the low dose group (5 mg 
or 10 mg) and 16.94 for the high dose group (10 mg or 20 mg) as compared with an improvement of 
7.09 in the placebo group. 
 
The efficacy of aripiprazole in paediatric subjects with Tourette’s syndrome (aripiprazole: n = 32, 
placebo: n = 29) was also evaluated over a flexible dose range of 2 mg/day to 20 mg/day and a starting 
dose of 2 mg, in a 10 week, randomised, double blind, placebo-controlled study conducted in South-
Korea. Patients were 6 to 18 years and presented an average score of 29 on TTS-YGTSS at baseline. 
Aripiprazole group showed an improvement of 14.97 on TTS-YGTSS change from baseline to 
week 10 as compared with an improvement of 9.62 in the placebo group. 
 
In both of these short-term trials, the clinical relevance of the efficacy findings has not been 
established, considering the magnitude of treatment effect compared to the large placebo effect and the 
unclear effects regarding psycho-social functioning. No long-term data are available with regard to the 
efficacy and the safety of aripiprazole in this fluctuating disorder. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
ABILIFY in one or more subsets of the paediatric population in the treatment of schizophrenia and in 
the treatment of bipolar affective disorder (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Aripiprazole is well absorbed, with peak plasma concentrations occurring within 3 to 5 hours after 
dosing. Aripiprazole undergoes minimal pre-systemic metabolism. The absolute oral bioavailability of 
the tablet formulation is 87 %. There is no effect of a high fat meal on the pharmacokinetics of 
aripiprazole. 
 
Distribution 
 
Aripiprazole is widely distributed throughout the body with an apparent volume of distribution of 
4.9 L/kg, indicating extensive extravascular distribution. At therapeutic concentrations, aripiprazole 
and dehydro-aripiprazole are greater than 99 % bound to serum proteins, binding primarily to albumin. 
 
Biotransformation 
 
Aripiprazole is extensively metabolised by the liver primarily by three biotransformation pathways: 
dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 
enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is 
catalysed by CYP3A4. Aripiprazole is the predominant medicinal product moiety in systemic 
circulation. At steady state, dehydro-aripiprazole, the active metabolite, represents about 40 % of 
aripiprazole AUC in plasma. 
 
Elimination 



 37 

 
The mean elimination half-lives for aripiprazole are approximately 75 hours in extensive metabolisers 
of CYP2D6 and approximately 146 hours in poor metabolisers of CYP2D6. 
 
The total body clearance of aripiprazole is 0.7 mL/min/kg, which is primarily hepatic. 
 
Following a single oral dose of [14C]-labelled aripiprazole, approximately 27 % of the administered 
radioactivity was recovered in the urine and approximately 60 % in the faeces. Less than 1 % of 
unchanged aripiprazole was excreted in the urine and approximately 18 % was recovered unchanged 
in the faeces. 
 
Paediatric population 
 
The pharmacokinetics of aripiprazole and dehydro-aripiprazole in paediatric patients 10 to 17 years of 
age were similar to those in adults after correcting for the differences in body weights. 
 
Pharmacokinetics in special patient groups 
 
Elderly 
There are no differences in the pharmacokinetics of aripiprazole between healthy elderly and younger 
adult subjects, nor is there any detectable effect of age in a population pharmacokinetic analysis in 
schizophrenic patients. 
 
Gender 
There are no differences in the pharmacokinetics of aripiprazole between healthy male and female 
subjects nor is there any detectable effect of gender in a population pharmacokinetic analysis in 
schizophrenic patients. 
 
Smoking 
Population pharmacokinetic evaluation has revealed no evidence of clinically significant effects from 
smoking on the pharmacokinetics of aripiprazole. 
 
Race 
Population pharmacokinetic evaluation showed no evidence of race-related differences on the 
pharmacokinetics of aripiprazole. 
 
Renal impairment 
The pharmacokinetic characteristics of aripiprazole and dehydro-aripiprazole were found to be similar 
in patients with severe renal disease compared to young healthy subjects. 
 
Hepatic impairment 
A single-dose study in subjects with varying degrees of liver cirrhosis (Child-Pugh Classes A, B, 
and C) did not reveal a significant effect of hepatic impairment on the pharmacokinetics of 
aripiprazole and dehydro-aripiprazole, but the study included only 3 patients with Class C liver 
cirrhosis, which is insufficient to draw conclusions on their metabolic capacity. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction 
and development. 
 
Toxicologically significant effects were observed only at doses or exposures that were sufficiently in 
excess of the maximum human dose or exposure, indicating that these effects were limited or of no 
relevance to clinical use. These included: dose-dependent adrenocortical toxicity (lipofuscin pigment 
accumulation and/or parenchymal cell loss) in rats after 104 weeks at 20 mg/kg/day to 60 mg/kg/day 
(3 to 10 times the mean steady-state AUC at the maximum recommended human dose) and increased 



 38 

adrenocortical carcinomas and combined adrenocortical adenomas/carcinomas in female rats at 
60 mg/kg/day (10 times the mean steady-state AUC at the maximum recommended human dose). The 
highest nontumorigenic exposure in female rats was 7 times the human exposure at the recommended 
dose. 
 
An additional finding was cholelithiasis as a consequence of precipitation of sulphate conjugates of 
hydroxy metabolites of aripiprazole in the bile of monkeys after repeated oral dosing at 25 mg/kg/day 
to 125 mg/kg/day (1 to 3 times the mean steady-state AUC at the maximum recommended clinical 
dose or 16 to 81 times the maximum recommended human dose based on mg/m2). However, the 
concentrations of the sulphate conjugates of hydroxy aripiprazole in human bile at the highest dose 
proposed, 30 mg per day, were no more than 6 % of the bile concentrations found in the monkeys in 
the 39-week study and are well below (6 %) their limits of in vitro solubility. 
 
In repeat-dose studies in juvenile rats and dogs, the toxicity profile of aripiprazole was comparable to 
that observed in adult animals, and there was no evidence of neurotoxicity or adverse reactions on 
development. 
 
Based on results of a full range of standard genotoxicity tests, aripiprazole was considered non-
genotoxic. Aripiprazole did not impair fertility in reproductive toxicity studies. Developmental 
toxicity, including dose-dependent delayed foetal ossification and possible teratogenic effects, were 
observed in rats at doses resulting in subtherapeutic exposures (based on AUC) and in rabbits at doses 
resulting in exposures 3 and 11 times the mean steady-state AUC at the maximum recommended 
clinical dose. Maternal toxicity occurred at doses similar to those eliciting developmental toxicity. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
 
Calcium silicate 
Croscarmellose sodium 
Crospovidone 
Silicon dioxide 
Xylitol 
Microcrystalline cellulose 
Aspartame (E 951) 
Acesulfame potassium 
Vanilla flavour (including vanillin, ethyl vanillin and lactose) 
Tartaric acid 
Magnesium stearate 
 
Tablet coat 
 
ABILIFY 10 mg orodispersible tablets 
Red iron oxide (E 172) 
 
ABILIFY 15 mg orodispersible tablets 
Yellow iron oxide (E 172) 
 
ABILIFY 30 mg orodispersible tablets 
Red iron oxide (E 172) 
 
6.2 Incompatibilities 
 
Not applicable. 



 39 

 
6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Store in the original package in order to protect from moisture. 
 
6.5 Nature and contents of container 
 
Aluminium perforated unit dose blisters in cartons of 14 × 1, 28 × 1, 49 × 1 tablets. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
ABILIFY 10 mg orodispersible tablets 
EU/1/04/276/024 (10 mg, 14 × 1 orodispersible tablets) 
EU/1/04/276/025 (10 mg, 28 × 1 orodispersible tablets) 
EU/1/04/276/026 (10 mg, 49 × 1 orodispersible tablets) 
 
ABILIFY 15 mg orodispersible tablets 
EU/1/04/276/027 (15 mg, 14 × 1 orodispersible tablets) 
EU/1/04/276/028 (15 mg, 28 × 1 orodispersible tablets) 
EU/1/04/276/029 (15 mg, 49 × 1 orodispersible tablets) 
 
ABILIFY 30 mg orodispersible tablets 
EU/1/04/276/030 (30 mg, 14 × 1 orodispersible tablets) 
EU/1/04/276/031 (30 mg, 28 × 1 orodispersible tablets) 
EU/1/04/276/032 (30 mg, 49 × 1 orodispersible tablets) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 04 June 2004 
Date of latest renewal: 04 June 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 



 40 

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 

http://www.ema.europa.eu/


 41 

1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 1 mg/mL oral solution 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each mL oral solution contains 1 mg of aripiprazole. 
 
Excipients with known effect (per mL) 
200 mg fructose, 400 mg sucrose, 1.8 mg methyl parahydroxybenzoate (E218), 0.2 mg propyl 
parahydroxybenzoate (E 216) 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Oral solution 
Clear, colourless to light yellow liquid solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
ABILIFY is indicated for the treatment of schizophrenia in adults and in adolescents aged 15 years 
and older. 
 
ABILIFY is indicated for the treatment of moderate to severe manic episodes in Bipolar I Disorder 
and for the prevention of a new manic episode in adults who experienced predominantly manic 
episodes and whose manic episodes responded to aripiprazole treatment (see section 5.1). 
 
ABILIFY is indicated for the treatment up to 12 weeks of moderate to severe manic episodes in 
Bipolar I Disorder in adolescents aged 13 years and older (see section 5.1). 
 
4.2 Posology and method of administration 
 
Posology 
 
Adults 
 
Schizophrenia: the recommended starting dose for ABILIFY is 10 mg/day or 15 mg/day (i.e. 10 mL or 
15 mL solution/day) with a maintenance dose of 15 mg/day administered on a once-a-day schedule 
without regard to meals. ABILIFY is effective in a dose range of 10 mg/day to 30 mg/day (i.e. 10 mL 
to 30 mL solution/day). Enhanced efficacy at doses higher than a daily dose of 15 mg has not been 
demonstrated although individual patients may benefit from a higher dose. The maximum daily dose 
should not exceed 30 mg. 
 
Manic episodes in Bipolar I Disorder: the recommended starting dose for ABILIFY is 15 mg (i.e. 
15 mL solution/day) administered on a once-a-day schedule without regard to meals as monotherapy 
or combination therapy (see section 5.1). Some patients may benefit from a higher dose. The 
maximum daily dose should not exceed 30 mg. 
 
Recurrence prevention of manic episodes in Bipolar I Disorder: for preventing recurrence of manic 
episodes in patients, who have been receiving aripiprazole as monotherapy or combination therapy, 
continue therapy at the same dose. Adjustments of daily dosage, including dose reduction should be 



 42 

considered on the basis of clinical status. 
 
Paediatric population 
 
Schizophrenia in adolescents aged 15 years and older: the recommended dose for ABILIFY is 
10 mg/day administered on a once-a-day schedule without regard to meals. Treatment should be 
initiated at 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 dose of 10 mg. When appropriate, subsequent dose increases 
should be administered in 5 mg increments without exceeding the maximum daily dose of 30 mg (see 
section 5.1). ABILIFY is effective in a dose range of 10 mg/day to 30 mg/day. Enhanced efficacy at 
doses higher than a daily dose of 10 mg has not been demonstrated although individual patients may 
benefit from a higher dose. 
ABILIFY is not recommended for use in patients with schizophrenia below 15 years of age due to 
insufficient data on safety and efficacy (see sections 4.8 and 5.1). 
 
Manic episodes in Bipolar I Disorder in adolescents aged 13 years and older: the recommended dose 
for ABILIFY is 10 mg/day administered on a once-a-day schedule without regard to meals. Treatment 
should be initiated at 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 dose of 10 mg. The treatment duration should be the 
minimum necessary for symptom control and must not exceed 12 weeks. Enhanced efficacy at doses 
higher than a daily dose of 10 mg has not been demonstrated, and a daily dose of 30 mg is associated 
with a substantially higher incidence of significant adverse reactions including EPS related events, 
somnolence, fatigue and weight gain (see section 4.8). Doses higher than 10 mg/day should therefore 
only be used in exceptional cases and with close clinical monitoring (see sections 4.4, 4.8 and 5.1). 
Younger patients are at increased risk of experiencing adverse events associated with aripiprazole. 
Therefore, ABILIFY is not recommended for use in patients below 13 years of age (see sections 4.8 
and 5.1). 
 
Irritability associated with autistic disorder: the safety and efficacy of ABILIFY in children and 
adolescents aged below 18 years have not yet been established. Currently available data are described 
in section 5.1 but no recommendation on a posology can be made. 
 
Tics associated with Tourette’s disorder: the safety and efficacy of ABILIFY in children and 
adolescents 6 to 18 years of age have not yet been established. Currently available data are described 
in section 5.1 but no recommendation on a posology can be made. 
 
Special populations 
 
Hepatic impairment 
No dosage adjustment is required for patients with mild to moderate hepatic impairment. In patients 
with severe hepatic impairment, the data available are insufficient to establish recommendations. In 
these patients dosing should be managed cautiously. However, the maximum daily dose of 30 mg 
should be used with caution in patients with severe hepatic impairment (see section 5.2). 
 
Renal impairment 
No dosage adjustment is required in patients with renal impairment. 
 
Elderly 
The safety and efficacy of ABILIFY in the treatment of schizophrenia or manic episodes in Bipolar I 
Disorder in patients aged 65 years and older has not been established. Owing to the greater sensitivity 
of this population, a lower starting dose should be considered when clinical factors warrant (see 
section 4.4). 
 
Gender 
No dosage adjustment is required for female patients as compared to male patients (see section 5.2). 
 
Smoking status 



 43 

According to the metabolic pathway of aripiprazole no dosage adjustment is required for smokers (see 
section 4.5). 
 
Dose adjustments due to interactions 
When concomitant administration of strong CYP3A4 or CYP2D6 inhibitors with aripiprazole occurs, 
the aripiprazole dose should be reduced. When the CYP3A4 or CYP2D6 inhibitor is withdrawn from 
the combination therapy, aripiprazole dose should then be increased (see section 4.5). 
When concomitant administration of strong CYP3A4 inducers with aripiprazole occurs, the 
aripiprazole dose should be increased. When the CYP3A4 inducer is withdrawn from the combination 
therapy, the aripiprazole dose should then be reduced to the recommended dose (see section 4.5). 
 
Method of administration 
 
ABILIFY is for oral use. 
 
Orodispersible tablets or oral solution may be used as an alternative to ABILIFY tablets for patients 
who have difficulty swallowing ABILIFY tablets (see section 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
During antipsychotic treatment, improvement in the patient's clinical condition may take several days 
to some weeks. Patients should be closely monitored throughout this period. 
 
Suicidality 
 
The occurrence of suicidal behaviour is inherent in psychotic illnesses and mood disorders and in 
some cases has been reported early after initiation or switch of antipsychotic treatment, including 
treatment with aripiprazole (see section 4.8). Close supervision of high-risk patients should 
accompany antipsychotic treatment. 
 
Cardiovascular disorders 
 
Aripiprazole should be used with caution in patients with known cardiovascular disease (history of 
myocardial infarction or ischaemic heart disease, heart failure, or conduction abnormalities), 
cerebrovascular disease, conditions which would predispose patients to hypotension (dehydration, 
hypovolemia, and treatment with antihypertensive medicinal products) or hypertension, including 
accelerated or malignant. Cases of venous thromboembolism (VTE) have been reported with 
antipsychotic medicinal products. Since patients treated with antipsychotics often present with 
acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during 
treatment with aripiprazole and preventive measures undertaken. 
 
QT prolongation 
 
In clinical trials of aripiprazole, the incidence of QT prolongation was comparable to placebo. 
Aripiprazole should be used with caution in patients with a family history of QT prolongation (see 
section 4.8). 
 
Tardive dyskinesia 
 
In clinical trials of one year or less duration, there were uncommon reports of treatment emergent 
dyskinesia during treatment with aripiprazole. If signs and symptoms of tardive dyskinesia appear in a 
patient on aripiprazole, dose reduction or discontinuation should be considered (see section 4.8). These 
symptoms can temporally deteriorate or can even arise after discontinuation of treatment. 



 44 

 
Other extrapyramidal symptoms 
 
In paediatric clinical trials of aripiprazole akathisia and Parkinsonism were observed. If signs and 
symptoms of other EPS appear in a patient taking aripiprazole, dose reduction and close clinical 
monitoring should be considered. 
 
Neuroleptic Malignant Syndrome (NMS) 
 
NMS is a potentially fatal symptom complex associated with antipsychotics. In clinical trials, rare 
cases of NMS were reported during treatment with aripiprazole. Clinical manifestations of NMS are 
hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular 
pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may 
include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. 
However, elevated creatine phosphokinase and rhabdomyolysis, not necessarily in association with 
NMS, have also been reported. If a patient develops signs and symptoms indicative of NMS, or 
presents with unexplained high fever without additional clinical manifestations of NMS, all 
antipsychotics, including aripiprazole, must be discontinued. 
 
Seizure 
 
In clinical trials, uncommon cases of seizure were reported during treatment with aripiprazole. 
Therefore, aripiprazole should be used with caution in patients who have a history of seizure disorder 
or have conditions associated with seizures (see section 4.8). 
 
Elderly patients with dementia-related psychosis 
 
Increased mortality 
In three placebo-controlled trials (n = 938; mean age: 82.4 years; range: 56 to 99 years) of aripiprazole 
in elderly patients with psychosis associated with Alzheimer's disease, patients treated with 
aripiprazole were at increased risk of death compared to placebo. The rate of death in aripiprazole-
treated patients was 3.5 % compared to 1.7 % in the placebo group. Although the causes of deaths 
were varied, most of the deaths appeared to be either cardiovascular (e.g. heart failure, sudden death) 
or infectious (e.g. pneumonia) in nature (see section 4.8). 
 
Cerebrovascular adverse reactions 
In the same trials, cerebrovascular adverse reactions (e.g. stroke, transient ischaemic attack), including 
fatalities, were reported in patients (mean age: 84 years; range: 78 to 88 years). Overall, 1.3 % of 
aripiprazole-treated patients reported cerebrovascular adverse reactions compared with 0.6 % of 
placebo-treated patients in these trials. This difference was not statistically significant. However, in 
one of these trials, a fixed-dose trial, there was a significant dose response relationship for 
cerebrovascular adverse reactions in patients treated with aripiprazole (see section 4.8). 
 
Aripiprazole is not indicated for the treatment of patients with dementia-related psychosis. 
 
Hyperglycaemia and diabetes mellitus 
 
Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or 
death, has been reported in patients treated with atypical antipsychotics, including aripiprazole. Risk 
factors that may predispose patients to severe complications include obesity and family history of 
diabetes. In clinical trials with aripiprazole, there were no significant differences in the incidence rates 
of hyperglycaemia-related adverse reactions (including diabetes) or in abnormal glycaemia laboratory 
values compared to placebo. Precise risk estimates for hyperglycaemia-related adverse reactions in 
patients treated with aripiprazole and with other atypical antipsychotics are not available to allow 
direct comparisons. Patients treated with any antipsychotics, including aripiprazole, should be 
observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and 
weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be 



 45 

monitored regularly for worsening of glucose control (see section 4.8). 
 
Hypersensitivity 
 
Hypersensitivity reactions, characterised by allergic symptoms, may occur with aripiprazole (see 
section 4.8). 
 
Weight gain 
 
Weight gain is commonly seen in schizophrenic and bipolar mania patients due to co-morbidities, use 
of antipsychotics known to cause weight gain, poorly managed life-style, and might lead to severe 
complications. Weight gain has been reported post-marketing among patients prescribed aripiprazole. 
When seen, it is usually in those with significant risk factors such as history of diabetes, thyroid 
disorder or pituitary adenoma. In clinical trials aripiprazole has not been shown to induce clinically 
relevant weight gain in adults (see section 5.1). In clinical trials of adolescent patients with bipolar 
mania, aripiprazole has been shown to be associated with weight gain after 4 weeks of treatment. 
Weight gain should be monitored in adolescent patients with bipolar mania. If weight gain is clinically 
significant, dose reduction should be considered (see section 4.8). 
 
Dysphagia 
 
Oesophageal dysmotility and aspiration have been associated with the use of antipsychotics, including 
aripiprazole. Aripiprazole should be used cautiously in patients at risk for aspiration pneumonia. 
 
Pathological gambling and other impulse control disorders 
 
Patients can experience increased urges, particularly for gambling, and the inability to control these 
urges while taking aripiprazole. Other urges, reported, include: increased sexual urges, compulsive 
shopping, binge or compulsive eating, and other impulsive and compulsive behaviours. It is important 
for prescribers to ask patients or their caregivers specifically about the development of new or 
increased gambling urges, sexual urges, compulsive shopping, binge or compulsive eating, or other 
urges while being treated with aripiprazole. It should be noted that impulse-control symptoms can be 
associated with the underlying disorder; however, in some cases, urges were reported to have stopped 
when the dose was reduced or the medication was discontinued. Impulse control disorders may result 
in harm to the patient and others if not recognised. Consider dose reduction or stopping the medication 
if a patient develops such urges while taking aripiprazole (see section 4.8). 
 
Fructose and sucrose 
 
The oral solution contains fructose and sucrose. Fructose may damage teeth. Sucrose may be harmful 
to the teeth. Patients with rare hereditary problems of fructose intolerance, glucose-galactose 
malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product. 
 
Parahydroxybenzoate 
 
The oral solution contains methyl parahydroxybenzoate and propyl parahydroxybenzoate. May cause 
allergic reactions (possibly delayed). 
 
Sodium 
 
The oral solution contains sodium. This medicinal product contains less than 1 mmol sodium (23 mg) 
per dosage unit, that is to say essentially ‘sodium-free’. 
 
Patients with attention deficit hyperactivity disorder (ADHD) comorbidity 
 
Despite the high comorbidity frequency of Bipolar I Disorder and ADHD, very limited safety data are 
available on concomitant use of aripiprazole and stimulants; therefore, extreme caution should be 



 46 

taken when these medicinal products are co-administered. 
 
Falls 
 
Aripiprazole may cause somnolence, postural hypotension, motor and sensory instability, which may 
lead to falls. Caution should be taken when treating patients at higher risk, and a lower starting dose 
should be considered (e.g., elderly or debilitated patients; see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Due to its α1-adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of 
certain antihypertensive medicinal products. 
 
Given the primary CNS effects of aripiprazole, caution should be used when aripiprazole is 
administered in combination with alcohol or other CNS medicinal products with overlapping adverse 
reactions such as sedation (see section 4.8). 
 
If aripiprazole is administered concomitantly with medicinal products known to cause QT 
prolongation or electrolyte imbalance, caution should be used. 
 
Potential for other medicinal products to affect aripiprazole 
 
A gastric acid blocker, the H2 antagonist famotidine, reduces aripiprazole rate of absorption but this 
effect is deemed not clinically relevant. Aripiprazole is metabolised by multiple pathways involving 
the CYP2D6 and CYP3A4 enzymes but not CYP1A enzymes. Thus, no dosage adjustment is required 
for smokers. 
 
Quinidine and other CYP2D6 inhibitors 
In a clinical trial in healthy subjects, a strong inhibitor of CYP2D6 (quinidine) increased aripiprazole 
AUC by 107 %, while Cmax was unchanged. The AUC and Cmax of dehydro-aripiprazole, the active 
metabolite, decreased by 32 % and 47 %, respectively. Aripiprazole dose should be reduced to 
approximately one-half of its prescribed dose when concomitant administration of aripiprazole with 
quinidine occurs. Other strong inhibitors of CYP2D6, such as fluoxetine and paroxetine, may be 
expected to have similar effects and similar dose reductions should therefore be applied. 
 
Ketoconazole and other CYP3A4 inhibitors 
In a clinical trial in healthy subjects, a strong inhibitor of CYP3A4 (ketoconazole) increased 
aripiprazole AUC and Cmax by 63 % and 37 %, respectively. The AUC and Cmax of dehydro-
aripiprazole increased by 77 % and 43 %, respectively. In CYP2D6 poor metabolisers, concomitant 
use of strong inhibitors of CYP3A4 may result in higher plasma concentrations of aripiprazole 
compared to that in CYP2D6 extensive metabolizers. When considering concomitant administration of 
ketoconazole or other strong CYP3A4 inhibitors with aripiprazole, potential benefits should outweigh 
the potential risks to the patient. When concomitant administration of ketoconazole with aripiprazole 
occurs, aripiprazole dose should be reduced to approximately one-half of its prescribed dose. Other 
strong inhibitors of CYP3A4, such as itraconazole and HIV protease inhibitors may be expected to 
have similar effects and similar dose reductions should therefore be applied (see section 4.2). Upon 
discontinuation of the CYP2D6 or CYP3A4 inhibitor, the dosage of aripiprazole should be increased 
to the level prior to the initiation of the concomitant therapy. When weak inhibitors of CYP3A4 (e.g. 
diltiazem) or CYP2D6 (e.g. escitalopram) are used concomitantly with aripiprazole, modest increases 
in plasma aripiprazole concentrations may be expected. 
 
Carbamazepine and other CYP3A4 inducers 
Following concomitant administration of carbamazepine, a strong inducer of CYP3A4, and oral 
aripiprazole to patients with schizophrenia or schizoaffective disorder, the geometric means of Cmax 
and AUC for aripiprazole were 68 % and 73 % lower, respectively, compared to when aripiprazole 
(30 mg) was administered alone. Similarly, for dehydro-aripiprazole the geometric means of Cmax and 
AUC after carbamazepine co-administration were 69 % and 71 % lower, respectively, than those 



 47 

following treatment with aripiprazole alone. Aripiprazole dose should be doubled when concomitant 
administration of aripiprazole occurs with carbamazepine. Concomitant administration of aripiprazole 
and other inducers of CYP3A4 (such as rifampicin, rifabutin, phenytoin, phenobarbital, primidone, 
efavirenz, nevirapine and St. John's Wort) may be expected to have similar effects and similar dose 
increases should therefore be applied. Upon discontinuation of strong CYP3A4 inducers, the dosage of 
aripiprazole should be reduced to the recommended dose. 
 
Valproate and lithium 
When either valproate or lithium was administered concomitantly with aripiprazole, there was no 
clinically significant change in aripiprazole concentrations and therefore no dose adjustment is 
necessary when either valproate or lithium is administered with aripiprazole. 
 
Potential for aripiprazole to affect other medicinal products 
 
In clinical studies, 10 mg/day to 30 mg/day doses of aripiprazole had no significant effect on the 
metabolism of substrates of CYP2D6 (dextromethorphan/3-methoxymorphinan ratio), 
CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP3A4 (dextromethorphan). Additionally, 
aripiprazole and dehydro-aripiprazole did not show potential for altering CYP1A2-mediated 
metabolism in vitro. Thus, aripiprazole is unlikely to cause clinically important medicinal product 
interactions mediated by these enzymes. 
 
When aripiprazole was administered concomitantly with either valproate, lithium or lamotrigine, there 
was no clinically important change in valproate, lithium or lamotrigine concentrations. 
 
Serotonin syndrome 
Cases of serotonin syndrome have been reported in patients taking aripiprazole, and possible signs and 
symptoms for this condition can occur especially in cases of concomitant use with other serotonergic 
medicinal products, such as selective serotonin reuptake inhibitor/selective serotonin noradrenaline 
reuptake inhibitor (SSRI/SNRI), or with medicinal products that are known to increase aripiprazole 
concentrations (see section 4.8). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate and well-controlled trials of aripiprazole in pregnant women. Congenital 
anomalies have been reported; however, causal relationship with aripiprazole could not be established. 
Animal studies could not exclude potential developmental toxicity (see section 5.3). Patients must be 
advised to notify their physician if they become pregnant or intend to become pregnant during 
treatment with aripiprazole. Due to insufficient safety information in humans and concerns raised by 
animal reproductive studies, this medicinal product should not be used in pregnancy unless the 
expected benefit clearly justifies the potential risk to the foetus. 
 
Newborn infants exposed to antipsychotics (including aripiprazole) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborn 
infants should be monitored carefully (see section 4.8). 
 
Breast-feeding 
 
Aripiprazole/metabolites are excreted in human milk. A decision must be made whether to discontinue 
breast-feeding or to discontinue/abstain from aripiprazole therapy taking into account the benefit of 
breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 



 48 

Aripiprazole did not impair fertility based on data from reproductive toxicity studies. 
 
4.7 Effects on ability to drive and use machines 
 
Aripiprazole has minor to moderate influence on the ability to drive and use machines due to potential 
nervous system and visual effects, such as sedation, somnolence, syncope, vision blurred, diplopia (see 
section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most commonly reported adverse reactions in placebo-controlled trials were akathisia and nausea 
each occurring in more than 3 % of patients treated with oral aripiprazole. 
 
Tabulated list of adverse reactions 
 
The incidences of the Adverse Drug Reactions (ADRs) associated with aripiprazole therapy are 
tabulated below. The table is based on adverse events reported during clinical trials and/or post-
marketing use. 
 
All ADRs are listed by system organ class and frequency; very common (≥ 1/10), common (≥ 1/100 to 
< 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and 
not known (cannot be estimated from the available data). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness. 
 
The frequency of adverse reactions reported during post-marketing use cannot be determined as they 
are derived from spontaneous reports. Consequently, the frequency of these adverse events is qualified 
as "not known". 
 
 Common Uncommon Not known 

 
Blood and 
lymphatic system 
disorders 

  Leukopenia 
Neutropenia 
Thrombocytopenia 

Immune system 
disorders 

  Allergic reaction (e.g. 
anaphylactic reaction, 
angioedema including swollen 
tongue, tongue oedema, face 
oedema, pruritus allergic, or 
urticaria) 

Endocrine 
disorders 

 Hyperprolactinaemia 
 

Diabetic hyperosmolar coma 
Diabetic ketoacidosis 
 

Metabolism and 
nutrition disorders 

Diabetes mellitus Hyperglycaemia Hyponatremia 
Anorexia 

Psychiatric 
disorders 

Insomnia 
Anxiety 
Restlessness 

Depression 
Hypersexuality 

Suicide attempt, suicidal ideation 
and completed suicide (see 
section 4.4) 
Pathological gambling 
Impulse-control disorder 
Binge eating 
Compulsive shopping 
Poriomania 
Aggression 
Agitation 
Nervousness  



 49 

 Common Uncommon Not known 
 

Nervous system 
disorders 

Akathisia 
Extrapyramidal 
disorder 
Tremor 
Headache 
Sedation 
Somnolence 
Dizziness 

Tardive dyskinesia 
Dystonia 
Restless legs 
syndrome 
 

Neuroleptic Malignant Syndrome 
Grand mal convulsion 
Serotonin syndrome 
Speech disorder 
 

Eye disorders Vision blurred Diplopia 
Photophobia 

Oculogyric crisis 

Cardiac disorders  Tachycardia 
 

Sudden death unexplained  
Torsades de pointes 
Ventricular arrhythmia 
Cardiac arrest 
Bradycardia 

Vascular disorders  Orthostatic 
hypotension 
 

Venous thromboembolism 
(including pulmonary embolism 
and deep vein thrombosis) 
Hypertension 
Syncope 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Hiccups Aspiration pneumonia 
Laryngospasm 
Oropharyngeal spasm 
 

Gastrointestinal 
disorders 

Constipation 
Dyspepsia 
Nausea 
Salivary 
hypersecretion 
Vomiting 

 Pancreatitis 
Dysphagia 
Diarrhoea 
Abdominal discomfort 
Stomach discomfort 
 

Hepatobiliary 
disorders 

  Hepatic failure 
Hepatitis 
Jaundice 

Skin and 
subcutaneous tissue 
disorders 

  Rash 
Photosensitivity reaction 
Alopecia 
Hyperhidrosis 
Drug Reaction with Eosinophilia 
and Systemic Symptoms 
(DRESS) 

Musculoskeletal 
and connective 
tissue disorders 

  Rhabdomyolysis 
Myalgia 
Stiffness 

Renal and urinary 
disorders 

  Urinary incontinence 
Urinary retention 

Pregnancy, 
puerperium and 
perinatal conditions 

  Drug withdrawal syndrome 
neonatal (see section 4.6) 

Reproductive 
system and breast 
disorders 

  Priapism 

General disorders 
and administration 
site conditions 

Fatigue 
 

 Temperature regulation disorder 
(e.g. hypothermia, pyrexia) 
Chest pain 
Peripheral oedema 



 50 

 Common Uncommon Not known 
 

Investigations   Weight decreased 
Weight gain 
Alanine Aminotransferase 
increased 
Aspartate Aminotransferase 
increased 
Gamma-glutamyltransferase 
increased 
Alkaline phosphatase increased 
QT prolonged 
Blood glucose increased 
Glycosylated haemoglobin 
increased 
Blood glucose fluctuation 
Creatine phosphokinase increased 

 
Description of selected adverse reactions 
 
Adults 
 
Extrapyramidal symptoms (EPS) 
Schizophrenia: in a long-term 52-week controlled trial, aripiprazole-treated patients had an overall-
lower incidence (25.8 %) of EPS including Parkinsonism, akathisia, dystonia and dyskinesia compared 
with those treated with haloperidol (57.3 %). In a long-term 26-week placebo-controlled trial, the 
incidence of EPS was 19 % for aripiprazole-treated patients and 13.1 % for placebo-treated patients. In 
another long-term 26-week controlled trial, the incidence of EPS was 14.8 % for aripiprazole-treated 
patients and 15.1 % for olanzapine-treated patients. 
 
Manic episodes in Bipolar I Disorder: in a 12-week controlled trial, the incidence of EPS was 23.5 % 
for aripiprazole-treated patients and 53.3 % for haloperidol-treated patients. In another 12-week trial, 
the incidence of EPS was 26.6 % for patients treated with aripiprazole and 17.6 % for those treated 
with lithium. In the long-term 26-week maintenance phase of a placebo-controlled trial, the incidence 
of EPS was 18.2 % for aripiprazole-treated patients and 15.7 % for placebo-treated patients. 
 
Akathisia 
In placebo-controlled trials, the incidence of akathisia in bipolar patients was 12.1 % with aripiprazole 
and 3.2 % with placebo. In schizophrenia 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 muscle groups, may occur in 
susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of 
the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty 
breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur 
more frequently and with greater severity with high potency and at higher doses of first generation 
antipsychotic medicinal products. An elevated risk of acute dystonia is observed in males and younger 
age groups. 
 
Prolactin 
In clinical trials for the approved indications and post-marketing, both increase and decrease in serum 
prolactin as compared to baseline was observed with aripiprazole (section 5.1). 
 
Laboratory parameters 
Comparisons between aripiprazole and placebo in the proportions of patients experiencing potentially 
clinically significant changes in routine laboratory and lipid parameters (see section 5.1) revealed no 



 51 

medically important differences. Elevations of CPK (Creatine Phosphokinase), generally transient and 
asymptomatic, were observed in 3.5 % of aripiprazole treated patients as compared to 2.0 % of 
patients who received placebo. 
 
Paediatric population 
 
Schizophrenia in adolescents aged 15 years and older 
In a short-term placebo-controlled clinical trial involving 302 adolescents (13 to 17 years) with 
schizophrenia, the frequency and type of adverse reactions were similar to those in adults except for 
the following reactions that were reported more frequently in adolescents receiving aripiprazole than 
in adults receiving aripiprazole (and more frequently than placebo): 
Somnolence/sedation and extrapyramidal disorder were reported very commonly (≥ 1/10), and dry 
mouth, increased appetite, and orthostatic hypotension were reported commonly (≥ 1/100, < 1/10). 
The safety profile in a 26-week open-label extension trial was similar to that observed in the short-
term, placebo-controlled trial. 
The safety profile of a long-term, double-blind, placebo-controlled trial was also similar except for the 
following reactions that were reported more frequently than paediatric patients taking placebo: weight 
decreased, blood insulin increased, arrhythmia, and leukopenia were reported commonly (≥ 1/100, 
< 1/10). 
 
In the pooled adolescent schizophrenia population (13 to 17 years) with exposure up to 2 years, 
incidence of low serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) was 29.5 % 
and 48.3 %, respectively. In the adolescent (13 to 17 years) schizophrenia population with aripiprazole 
exposure of 5 mg to 30 mg up to 72 months, incidence of low serum prolactin levels in females 
(< 3 ng/mL) and males (< 2 ng/mL) was 25.6 % and 45.0 %, respectively. 
In two long-term trials with adolescent (13 to 17 years) schizophrenia and bipolar patients treated with 
aripiprazole, incidence of low serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) 
was 37.0 % and 59.4 %, respectively. 
 
Manic episodes in Bipolar I Disorder in adolescents aged 13 years and older 
The frequency and type of adverse reactions in adolescents with Bipolar I Disorder were similar to 
those in adults except for the following reactions: very commonly (≥ 1/10) somnolence (23.0 %), 
extrapyramidal disorder (18.4 %), akathisia (16.0 %), and fatigue (11.8 %); and commonly (≥ 1/100, 
< 1/10) abdominal pain upper, heart rate increased, weight increased, increased appetite, muscle 
twitching, and dyskinesia. 
 
The following adverse reactions had a possible dose response relationship; extrapyramidal disorder 
(incidences were 10 mg, 9.1 %; 30 mg, 28.8 %; placebo, 1.7 %); and akathisia (incidences were 
10 mg, 12.1 %; 30 mg, 20.3 %; placebo, 1.7 %). 
 
Mean changes in body weight in adolescents with Bipolar I Disorder at 12 and 30 weeks for 
aripiprazole were 2.4 kg and 5.8 kg, and for placebo 0.2 kg and 2.3 kg, respectively. 
 
In the paediatric population somnolence and fatigue were observed more frequently in patients with 
bipolar disorder compared to patients with schizophrenia. 
 
In the paediatric bipolar population (10 to 17 years) with exposure up to 30 weeks, incidence of low 
serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) was 28.0 % and 53.3 %, 
respectively. 
 
Pathological gambling and other impulse control disorders 
Pathological gambling, hypersexuality, compulsive shopping and binge or compulsive eating can 
occur in patients treated with aripiprazole (see section 4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 



 52 

professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Signs and symptoms 
 
In clinical trials and post-marketing experience, accidental or intentional acute overdose of 
aripiprazole alone was identified in adult patients with reported estimated doses up to 1,260 mg with 
no fatalities. The potentially medically important signs and symptoms observed included lethargy, 
increased blood pressure, somnolence, tachycardia, nausea, vomiting and diarrhoea. In addition, 
reports of accidental overdose with aripiprazole alone (up to 195 mg) in children have been received 
with no fatalities. The potentially medically serious signs and symptoms reported included 
somnolence, transient loss of consciousness and extrapyramidal symptoms. 
 
Management of overdose 
 
Management of overdose should concentrate on supportive therapy, maintaining an adequate airway, 
oxygenation and ventilation, and management of symptoms. The possibility of multiple medicinal 
product involvement should be considered. Therefore cardiovascular monitoring should be started 
immediately and should include continuous electrocardiographic monitoring to detect possible 
arrhythmias. Following any confirmed or suspected overdose with aripiprazole, close medical 
supervision and monitoring should continue until the patient recovers. 
 
Activated charcoal (50 g), administered one hour after aripiprazole, decreased aripiprazole Cmax by 
about 41 % and AUC by about 51 %, suggesting that charcoal may be effective in the treatment of 
overdose. 
 
Haemodialysis 
 
Although there is no information on the effect of haemodialysis in treating an overdose with 
aripiprazole, haemodialysis is unlikely to be useful in overdose management since aripiprazole is 
highly bound to plasma proteins. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Psycholeptics, other antipsychotics, ATC code: N05AX12 
 
Mechanism of action 
 
It has been proposed that aripiprazole’s efficacy in schizophrenia and Bipolar I Disorder is mediated 
through a combination of partial agonism at dopamine D2 and serotonin 5-HT1A receptors and 
antagonism of serotonin 5-HT2A receptors. Aripiprazole exhibited antagonist properties in animal 
models of dopaminergic hyperactivity and agonist properties in animal models of dopaminergic 
hypoactivity. Aripiprazole exhibited high binding affinity in vitro for dopamine D2 and D3, serotonin 
5-HT1A and 5-HT2A receptors and moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, 
alpha-1 adrenergic and histamine H1 receptors. Aripiprazole also exhibited moderate binding affinity 
for the serotonin reuptake site and no appreciable affinity for muscarinic receptors. Interaction with 
receptors other than dopamine and serotonin subtypes may explain some of the other clinical effects of 
aripiprazole. 
 
Aripiprazole doses ranging from 0.5 mg to 30 mg administered once a day to healthy subjects for 
2 weeks produced a dose-dependent reduction in the binding of 11C-raclopride, a D2/D3 receptor 
ligand, to the caudate and putamen detected by positron emission tomography. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 53 

 
Clinical efficacy and safety 
 
Adults 
 
Schizophrenia 
In three short-term (4 to 6 weeks) placebo-controlled trials involving 1,228 schizophrenic adult 
patients, presenting with positive or negative symptoms, aripiprazole was associated with statistically 
significantly greater improvements in psychotic symptoms compared to placebo. 
 
Aripiprazole is effective in maintaining the clinical improvement during continuation therapy in adult 
patients who have shown an initial treatment response. In a haloperidol-controlled trial, the proportion 
of responder patients maintaining response to medicinal product at 52-weeks was similar in both 
groups (aripiprazole 77 % and haloperidol 73 %). The overall completion rate was significantly higher 
for patients on aripiprazole (43 %) than for haloperidol (30 %). Actual scores in rating scales used as 
secondary endpoints, including PANSS and the Montgomery-Åsberg Depression Rating Scale 
(MADRS) showed a significant improvement over haloperidol. 
 
In a 26-week, placebo-controlled trial in adult stabilised patients with chronic schizophrenia, 
aripiprazole had significantly greater reduction in relapse rate, 34 % in aripiprazole group and 57 % in 
placebo. 
 
Weight gain 
In clinical trials aripiprazole has not been shown to induce clinically relevant weight gain. In a 
26-week, olanzapine-controlled, double-blind, multi-national study of schizophrenia which included 
314 adult patients and where the primary endpoint was weight gain, significantly less patients had at 
least 7 % weight gain over baseline (i.e. a gain of at least 5.6 kg for a mean baseline weight of 
~80.5 kg) on aripiprazole (n = 18, or 13 % of evaluable patients), compared to olanzapine (n = 45, or 
33 % of evaluable patients). 
 
Lipid parameters 
In a pooled analysis on lipid parameters from placebo controlled clinical trials in adults, aripiprazole 
has not been shown to induce clinically relevant alterations in levels of total cholesterol, triglycerides, 
High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL). 
 
Prolactin 
Prolactin levels were evaluated in all trials of all doses of aripiprazole (n = 28,242). The incidence of 
hyperprolactinaemia or increased serum prolactin in patients treated with aripiprazole (0.3 %) was 
similar to that of placebo (0.2 %). For patients receiving aripiprazole, the median time to onset was 
42 days and median duration was 34 days. 
 
The incidence of hypoprolactinaemia or decreased serum prolactin in patients treated with aripiprazole 
was 0.4 %, compared with 0.02 % for patients treated with placebo. For patients receiving 
aripiprazole, the median time to onset was 30 days and median duration was 194 days. 
 
Manic episodes in Bipolar I Disorder 
In two 3-week, flexible-dose, placebo-controlled monotherapy trials involving patients with a manic or 
mixed episode of Bipolar I Disorder, aripiprazole demonstrated superior efficacy to placebo in 
reduction of manic symptoms over 3 weeks. These trials included patients with or without psychotic 
features and with or without a rapid-cycling course. 
 
In one 3-week, fixed-dose, placebo-controlled monotherapy trial involving patients with a manic or 
mixed episode of Bipolar I Disorder, aripiprazole failed to demonstrate superior efficacy to placebo. 
 
In two 12-week, placebo- and active-controlled monotherapy trials in patients with a manic or mixed 
episode of Bipolar I Disorder, with or without psychotic features, aripiprazole demonstrated superior 
efficacy to placebo at week 3 and a maintenance of effect comparable to lithium or haloperidol at 



 54 

week 12. Aripiprazole also demonstrated a comparable proportion of patients in symptomatic 
remission from mania as lithium or haloperidol at week 12. 
 
In a 6-week, placebo-controlled trial involving patients with a manic or mixed episode of Bipolar I 
Disorder, with or without psychotic features, who were partially non-responsive to lithium or 
valproate monotherapy for 2 weeks at therapeutic serum levels, the addition of aripiprazole as 
adjunctive therapy resulted in superior efficacy in reduction of manic symptoms than lithium or 
valproate monotherapy. 
 
In a 26-week, placebo-controlled trial, followed by a 74-week extension, in manic patients who 
achieved remission on aripiprazole during a stabilization phase prior to randomisation, aripiprazole 
demonstrated superiority over placebo in preventing bipolar recurrence, primarily in preventing 
recurrence into mania but failed to demonstrate superiority over placebo in preventing recurrence into 
depression. 
 
In a 52-week, placebo-controlled trial, in patients with a current manic or mixed episode of Bipolar I 
Disorder who achieved sustained remission (Young Mania Rating Scale [YMRS] and MADRS with 
total scores ≤ 12) on aripiprazole (10 mg/day to 30 mg/day) adjunctive to lithium or valproate for 
12 consecutive weeks, adjunctive aripiprazole demonstrated superiority over placebo with a 46 % 
decreased risk (hazard ratio of 0.54) in preventing bipolar recurrence and a 65 % decreased risk 
(hazard ratio of 0.35) in preventing recurrence into mania over adjunctive placebo but failed to 
demonstrate superiority over placebo in preventing recurrence into depression. Adjunctive aripiprazole 
demonstrated superiority over placebo on the secondary outcome measure in Clinical Global 
Impression - Bipolar version (CGI-BP) Severity of Illness (SOI; mania) scores. In this trial, patients 
were assigned by investigators with either open-label lithium or valproate monotherapy to determine 
partial non-response. Patients were stabilised for at least 12 consecutive weeks with the combination 
of aripiprazole and the same mood stabilizer. Stabilized patients were then randomised to continue the 
same mood stabilizer with double-blind aripiprazole or placebo. Four mood stabilizer subgroups were 
assessed in the randomised phase: aripiprazole + lithium; aripiprazole + valproate; placebo + lithium; 
placebo + valproate. The Kaplan-Meier rates for recurrence to any mood episode for the adjunctive 
treatment arm were 16 % in aripiprazole + lithium and 18 % in aripiprazole + valproate compared to 
45 % in placebo + lithium and 19 % in placebo + valproate. 
 
Paediatric population 
 
Schizophrenia in adolescents 
In a 6-week placebo-controlled trial involving 302 schizophrenic adolescent patients (13 to 17 years), 
presenting with positive or negative symptoms, aripiprazole was associated with statistically 
significantly greater improvements in psychotic symptoms compared to placebo. In a sub-analysis of 
the adolescent patients between the ages of 15 to 17 years, representing 74 % of the total enrolled 
population, maintenance of effect was observed over the 26-week open-label extension trial. 
 
In a 60- to 89-week, randomised, double-blind, placebo-controlled trial in adolescent subjects 
(n = 146; ages 13 to 17 years) with schizophrenia, there was a statistically significant difference in the 
rate of relapse of psychotic symptoms between the aripiprazole (19.39 %) and placebo (37.50 %) 
groups. The point estimate of the hazard ratio (HR) was 0.461 (95 % confidence interval, 0.242 to 
0.879) in the full population. In subgroup analyses the point estimate of the HR was 0.495 for subjects 
13 to 14 years of age compared to 0.454 for subjects 15 to 17 years of age. However, the estimation of 
the HR for the younger (13 to 14 years) group was not precise, reflecting the smaller number of 
subjects in that group (aripiprazole, n = 29; placebo, n = 12), and the confidence interval for this 
estimation (ranging from 0.151 to 1.628) did not allow conclusions to be drawn on the presence of a 
treatment effect. In contrast the 95 % confidence interval for the HR in the older subgroup 
(aripiprazole, n = 69; placebo, n = 36) was 0.242 to 0.879 and hence a treatment effect could be 
concluded in the older patients. 
 
Manic episodes in Bipolar I Disorder in children and adolescents 
Aripiprazole was studied in a 30-week placebo-controlled trial involving 296 children and adolescents 



 55 

(10 to 17 years), who met DSM-IV criteria (Diagnostic and Statistical Manual of Mental Disorders) 
for Bipolar I Disorder with manic or mixed episodes with or without psychotic features and had a 
YMRS score ≥ 20 at baseline. Among the patients included in the primary efficacy analysis, 
139 patients had a current co-morbid diagnosis of ADHD. 
 
Aripiprazole was superior to placebo in change from baseline at week 4 and at week 12 on the Y-MRS 
total score. In a post-hoc analysis, the improvement over placebo was more pronounced in the patients 
with associated co-morbidity of ADHD compared to the group without ADHD, where there was no 
difference from placebo. Recurrence prevention was not established. 
The most common treatment-emergent adverse events among patients receiving 30 mg were 
extrapyramidal disorder (28.3 %), somnolence (27.3 %), headache (23.2 %), and nausea (14.1 %). 
Mean weight gain in the 30 weeks treatment-interval was 2.9 kg as compared to 0.98 kg in patients 
treated with placebo. 
 
Irritability associated with autistic disorder in paediatric patients (see section 4.2) 
Aripiprazole was studied in patients aged 6 to 17 years in two 8-week, placebo-controlled trials [one 
flexible-dose (2 mg/day to 15 mg/day) and one fixed-dose (5 mg/day, 10 mg/day, or 15 mg/day)] and 
in one 52-week open-label trial. Dosing in these trials was initiated at 2 mg/day, increased to 5 mg/day 
after one week, and increased by 5 mg/day in weekly increments to the target dose. Over 75 % of 
patients were less than 13 years of age. Aripiprazole demonstrated statistically superior efficacy 
compared to placebo on the Aberrant Behaviour Checklist Irritability subscale. However, the clinical 
relevance of this finding has not been established. The safety profile included weight gain and changes 
in prolactin levels. The duration of the long-term safety study was limited to 52 weeks. In the pooled 
trials, the incidence of low serum prolactin levels in females (< 3 ng/mL) and males (< 2 ng/mL) in 
aripiprazole-treated patients was 27/46 (58.7 %) and 258/298 (86.6 %), respectively. In the placebo-
controlled trials, the mean weight gain was 0.4 kg for placebo and 1.6 kg for aripiprazole. 
 
Aripiprazole was also studied in a placebo-controlled, long-term maintenance trial. After a 13 to 
26-week stabilisation on aripiprazole (2 mg/day to 15 mg/day) patients with a stable response were 
either maintained on aripiprazole or substituted to placebo for further 16 weeks. Kaplan-Meier relapse 
rates at week 16 were 35 % for aripiprazole and 52 % for placebo; the hazard ratio for relapse within 
16 weeks (aripiprazole/placebo) was 0.57 (non-statistically significant difference). The mean weight 
gain over the stabilisation phase (up to 26 weeks) on aripiprazole was 3.2 kg, and a further mean 
increase of 2.2 kg for aripiprazole as compared to 0.6 kg for placebo was observed in the second phase 
(16 weeks) of the trial. Extrapyramidal symptoms were mainly reported during the stabilisation phase 
in 17 % of patients, with tremor accounting for 6.5 %. 
 
Tics associated with Tourette’s disorder in paediatric patients (see section 4.2) 
The efficacy of aripiprazole was studied in paediatric subjects with Tourette’s disorder (aripiprazole: 
n = 99, placebo: n = 44) in a randomised, double-blind, placebo controlled, 8 week study using a fixed 
dose weight-based treatment group design over the dose range of 5 mg/day to 20 mg/day and a starting 
dose of 2 mg. Patients were 7 to 17 years of age and presented an average score of 30 on Total Tic 
Score on the Yale Global Tic Severity Scale (TTS-YGTSS) at baseline. Aripiprazole showed an 
improvement on TTS-YGTSS change from baseline to week 8 of 13.35, for the low dose group (5 mg 
or 10 mg) and 16.94 for the high dose group (10 mg or 20 mg) as compared with an improvement of 
7.09 in the placebo group. 
 
The efficacy of aripiprazole in paediatric subjects with Tourette’s syndrome (aripiprazole: n = 32, 
placebo: n = 29) was also evaluated over a flexible dose range of 2 mg/day to 20 mg/day and a starting 
dose of 2 mg, in a 10 week, randomised, double blind, placebo-controlled study conducted in South-
Korea. Patients were 6 to 18 years and presented an average score of 29 on TTS-YGTSS at baseline. 
Aripiprazole group showed an improvement of 14.97 on TTS-YGTSS change from baseline to 
week 10 as compared with an improvement of 9.62 in the placebo group. 
 
In both of these short-term trials, the clinical relevance of the efficacy findings has not been 
established, considering the magnitude of treatment effect compared to the large placebo effect and the 



 56 

unclear effects regarding psycho-social functioning. No long-term data are available with regard to the 
efficacy and the safety of aripiprazole in this fluctuating disorder. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
ABILIFY in one or more subsets of the paediatric population in the treatment of schizophrenia and in 
the treatment of bipolar affective disorder (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Aripiprazole is well absorbed, with peak plasma concentrations occurring within 3 to 5 hours after 
dosing. Aripiprazole undergoes minimal pre-systemic metabolism. The absolute oral bioavailability of 
the tablet formulation is 87 %. There is no effect of a high fat meal on the pharmacokinetics of 
aripiprazole. 
 
Distribution 
 
Aripiprazole is widely distributed throughout the body with an apparent volume of distribution of 
4.9 L/kg, indicating extensive extravascular distribution. At therapeutic concentrations, aripiprazole 
and dehydro-aripiprazole are greater than 99 % bound to serum proteins, binding primarily to albumin. 
 
Biotransformation 
 
Aripiprazole is extensively metabolised by the liver primarily by three biotransformation pathways: 
dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 
enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is 
catalysed by CYP3A4. Aripiprazole is the predominant medicinal product moiety in systemic 
circulation. At steady state, dehydro-aripiprazole, the active metabolite, represents about 40 % of 
aripiprazole AUC in plasma. 
 
Elimination 
 
The mean elimination half-lives for aripiprazole are approximately 75 hours in extensive metabolisers 
of CYP2D6 and approximately 146 hours in poor metabolisers of CYP2D6. 
 
The total body clearance of aripiprazole is 0.7 mL/min/kg, which is primarily hepatic. 
 
Following a single oral dose of [14C]-labelled aripiprazole, approximately 27 % of the administered 
radioactivity was recovered in the urine and approximately 60 % in the faeces. Less than 1 % of 
unchanged aripiprazole was excreted in the urine and approximately 18 % was recovered unchanged 
in the faeces. 
 
Oral Solution 
Aripiprazole is well absorbed when administered orally as the solution. At equivalent doses, the peak 
plasma concentrations of aripiprazole (Cmax) from the solution were somewhat higher but the systemic 
exposure (AUC) was equivalent to tablets. In a relative bioavailability study comparing the 
pharmacokinetics of 30 mg aripiprazole as the oral solution to 30 mg aripiprazole tablets in healthy 
subjects, the solution to the tablet ratio of geometric mean Cmax values was 122 % (n = 30). The single-
dose pharmacokinetics of aripiprazole was linear and dose-proportional. 
 
Paediatric population 
 
The pharmacokinetics of aripiprazole and dehydro-aripiprazole in paediatric patients 10 to 17 years of 
age were similar to those in adults after correcting for the differences in body weights. 
 
Pharmacokinetics in special patient groups 



 57 

 
Elderly 
There are no differences in the pharmacokinetics of aripiprazole between healthy elderly and younger 
adult subjects, nor is there any detectable effect of age in a population pharmacokinetic analysis in 
schizophrenic patients. 
 
Gender 
There are no differences in the pharmacokinetics of aripiprazole between healthy male and female 
subjects nor is there any detectable effect of gender in a population pharmacokinetic analysis in 
schizophrenic patients. 
 
Smoking 
Population pharmacokinetic evaluation has revealed no evidence of clinically significant effects from 
smoking on the pharmacokinetics of aripiprazole. 
 
Race 
Population pharmacokinetic evaluation showed no evidence of race-related differences on the 
pharmacokinetics of aripiprazole. 
 
Renal impairment 
The pharmacokinetic characteristics of aripiprazole and dehydro-aripiprazole were found to be similar 
in patients with severe renal disease compared to young healthy subjects. 
 
Hepatic impairment 
A single-dose study in subjects with varying degrees of liver cirrhosis (Child-Pugh Classes A, B, 
and C) did not reveal a significant effect of hepatic impairment on the pharmacokinetics of 
aripiprazole and dehydro-aripiprazole, but the study included only 3 patients with Class C liver 
cirrhosis, which is insufficient to draw conclusions on their metabolic capacity. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction 
and development. 
 
Toxicologically significant effects were observed only at doses or exposures that were sufficiently in 
excess of the maximum human dose or exposure, indicating that these effects were limited or of no 
relevance to clinical use. These included: dose-dependent adrenocortical toxicity (lipofuscin pigment 
accumulation and/or parenchymal cell loss) in rats after 104 weeks at 20 mg/kg/day to 60 mg/kg/day 
(3 to 10 times the mean steady-state AUC at the maximum recommended human dose) and increased 
adrenocortical carcinomas and combined adrenocortical adenomas/carcinomas in female rats at 
60 mg/kg/day (10 times the mean steady-state AUC at the maximum recommended human dose). The 
highest nontumorigenic exposure in female rats was 7 times the human exposure at the recommended 
dose. 
 
An additional finding was cholelithiasis as a consequence of precipitation of sulphate conjugates of 
hydroxy metabolites of aripiprazole in the bile of monkeys after repeated oral dosing at 25 mg/kg/day 
to 125 mg/kg/day (1 to 3 times the mean steady-state AUC at the maximum recommended clinical 
dose or 16 to 81 times the maximum recommended human dose based on mg/m2). However, the 
concentrations of the sulphate conjugates of hydroxy aripiprazole in human bile at the highest dose 
proposed, 30 mg per day, were no more than 6 % of the bile concentrations found in the monkeys in 
the 39-week study and are well below (6 %) their limits of in vitro solubility. 
 
In repeat-dose studies in juvenile rats and dogs, the toxicity profile of aripiprazole was comparable to 
that observed in adult animals, and there was no evidence of neurotoxicity or adverse reactions on 
development. 
 



 58 

Based on results of a full range of standard genotoxicity tests, aripiprazole was considered non-
genotoxic. Aripiprazole did not impair fertility in reproductive toxicity studies. Developmental 
toxicity, including dose-dependent delayed foetal ossification and possible teratogenic effects, were 
observed in rats at doses resulting in subtherapeutic exposures (based on AUC) and in rabbits at doses 
resulting in exposures 3 and 11 times the mean steady-state AUC at the maximum recommended 
clinical dose. Maternal toxicity occurred at doses similar to those eliciting developmental toxicity. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium edetate 
Fructose 
Glycerin 
Lactic acid 
Methyl parahydroxybenzoate (E 218) 
Propylene glycol 
Propyl parahydroxybenzoate (E 216) 
Sodium hydroxide 
Sucrose 
Purified water 
Orange flavour 
 
6.2 Incompatibilities 
 
The oral solution should not be diluted with other liquids or mixed with any food prior to 
administration. 
 
6.3 Shelf life 
 
3 years 
After first opening: 6 months. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
PET-bottles with polypropylene child-resistant closure containing 50 mL, 150 mL or 480 mL per 
bottle. 
Each carton contains 1 bottle and both a calibrated polypropylene measuring cup with a graduation 
interval of 2.5 mL and a calibrated polypropylene low-density polyethylene dropping pipette with a 
graduation interval of 0.5 mL. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 



 59 

Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/033 (1 mg/mL, 50 mL per bottle) 
EU/1/04/276/034 (1 mg/mL, 150 mL per bottle) 
EU/1/04/276/035 (1 mg/mL, 480 mL per bottle) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 04 June 2004 
Date of latest renewal: 04 June 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
 

http://www.ema.europa.eu/


 60 

1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 7.5 mg/mL solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each mL contains 7.5 mg of aripiprazole. Each vial contains 9.75 mg aripiprazole. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection 
 
Clear, colourless, aqueous solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
ABILIFY solution for injection is indicated for the rapid control of agitation and disturbed behaviours 
in adult patients with schizophrenia or with manic episodes in Bipolar I Disorder, when oral therapy is 
not appropriate. 
 
Treatment with ABILIFY solution for injection should be discontinued as soon as clinically 
appropriate and the use of oral aripiprazole should be initiated. 
 
4.2 Posology and method of administration 
 
Posology 
 
The recommended initial dose for ABILIFY solution for injection is 9.75 mg (1.3 mL), administered 
as a single intramuscular injection. The effective dose range of ABILIFY solution for injection is 
5.25 mg to 15 mg as a single injection. A lower dose of 5.25 mg (0.7 mL) may be given, on the basis 
of individual clinical status, which should also include consideration of medicinal products already 
administered either for maintenance or acute treatment (see section 4.5). 
 
A second injection may be administered 2 hours after the first injection, on the basis of individual 
clinical status and no more than three injections should be given in any 24-hour period. 
 
The maximum daily dose of aripiprazole is 30 mg (including all formulations of ABILIFY). 
 
If continued treatment is indicated with oral aripiprazole, see the Summary of Product Characteristics 
for ABILIFY tablets, ABILIFY orodispersible tablets, or ABILIFY oral solution. 
 
Special populations 
 
Paediatric population 
The safety and efficacy of ABILIFY solution for injection in children and adolescents aged 0 to 
17 years have not been established. No data are available. 
 
Hepatic impairment 
No dosage adjustment is required for patients with mild to moderate hepatic impairment. In patients 
with severe hepatic impairment, the data available are insufficient to establish recommendations. In 



 61 

these patients dosing should be managed cautiously. However, the maximum daily dose of 30 mg 
should be used with caution in patients with severe hepatic impairment (see section 5.2). 
 
Renal impairment 
No dosage adjustment is required in patients with renal impairment. 
 
Elderly 
The safety and efficacy of ABILIFY in the treatment of schizophrenia or manic episodes in Bipolar I 
Disorder in patients aged 65 years and older has not been established. Owing to the greater sensitivity 
of this population, a lower starting dose should be considered when clinical factors warrant (see 
section 4.4). 
 
Gender 
No dosage adjustment is required for female patients as compared to male patients (see section 5.2). 
 
Smoking status 
According to the metabolic pathway of aripiprazole no dosage adjustment is required for smokers (see 
section 4.5). 
 
Dose adjustments due to interactions 
When concomitant administration of strong CYP3A4 or CYP2D6 inhibitors with aripiprazole occurs, 
the aripiprazole dose should be reduced. When the CYP3A4 or CYP2D6 inhibitor is withdrawn from 
the combination therapy, aripiprazole dose should then be increased (see section 4.5). 
When concomitant administration of strong CYP3A4 inducers with aripiprazole occurs, the 
aripiprazole dose should be increased. When the CYP3A4 inducer is withdrawn from the combination 
therapy, the aripiprazole dose should then be reduced to the recommended dose (see section 4.5). 
 
Method of administration 
 
ABILIFY solution for injection is for intramuscular use. 
 
To enhance absorption and minimise variability, injection into the deltoid or deep within the gluteus 
maximus muscle, avoiding adipose regions, is recommended. 
 
ABILIFY solution for injection should not be administered intravenously or subcutaneously. 
 
It is ready to use and intended for short-term use only (see section 5.1). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
The efficacy of ABILIFY solution for injection in patients with agitation and disturbed behaviours has 
not been established related to conditions other than schizophrenia and manic episodes in Bipolar I 
Disorder. 
 
Simultaneous administration of injectable antipsychotics and parenteral benzodiazepine may be 
associated with excessive sedation and cardiorespiratory depression. If parenteral benzodiazepine 
therapy is deemed necessary in addition to aripiprazole solution for injection, patients should be 
monitored for excessive sedation and for orthostatic hypotension (see section 4.5). 
 
Patients receiving ABILIFY solution for injection should be observed for orthostatic hypotension. 
Blood pressure, pulse, respiratory rate and level of consciousness should be monitored regularly. 
 
The safety and efficacy of ABILIFY solution for injection has not been evaluated in patients with 



 62 

alcohol or medicinal product intoxication (either with prescribed or illicit medicinal products). 
 
During antipsychotic treatment, improvement in the patient's clinical condition may take several days 
to some weeks. Patients should be closely monitored throughout this period. 
 
Suicidality 
 
The occurrence of suicidal behaviour is inherent in psychotic illnesses and mood disorders and in 
some cases has been reported early after initiation or switch of antipsychotic treatment, including 
treatment with aripiprazole (see section 4.8). Close supervision of high-risk patients should 
accompany antipsychotic treatment. 
 
Cardiovascular disorders 
 
Aripiprazole should be used with caution in patients with known cardiovascular disease (history of 
myocardial infarction or ischaemic heart disease, heart failure, or conduction abnormalities), 
cerebrovascular disease, conditions which would predispose patients to hypotension (dehydration, 
hypovolemia, and treatment with antihypertensive medicinal products) or hypertension, including 
accelerated or malignant. Cases of venous thromboembolism (VTE) have been reported with 
antipsychotic medicinal products. Since patients treated with antipsychotics often present with 
acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during 
treatment with aripiprazole and preventive measures undertaken (see section 4.8). 
 
QT prolongation 
 
In clinical trials of treatment with oral aripiprazole, the incidence of QT prolongation was comparable 
to placebo. Aripiprazole should be used with caution in patients with a family history of QT 
prolongation (see section 4.8). 
 
Tardive dyskinesia 
 
In clinical trials of one year or less duration, there were uncommon reports of treatment emergent 
dyskinesia during treatment with aripiprazole. If signs and symptoms of tardive dyskinesia appear in a 
patient on aripiprazole, dose reduction or discontinuation should be considered (see section 4.8). These 
symptoms can temporally deteriorate or can even arise after discontinuation of treatment. 
 
Other extrapyramidal symptoms 
 
In paediatric clinical trials of aripiprazole akathisia and Parkinsonism were observed. If signs and 
symptoms of other EPS appear in a patient taking aripiprazole, dose reduction and close clinical 
monitoring should be considered. 
 
Neuroleptic Malignant Syndrome (NMS) 
 
NMS is a potentially fatal symptom complex associated with antipsychotics. In clinical trials, rare 
cases of NMS were reported during treatment with aripiprazole. Clinical manifestations of NMS are 
hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular 
pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may 
include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. 
However, elevated creatine phosphokinase and rhabdomyolysis, not necessarily in association with 
NMS, have also been reported. If a patient develops signs and symptoms indicative of NMS, or 
presents with unexplained high fever without additional clinical manifestations of NMS, all 
antipsychotics, including aripiprazole, must be discontinued. 
 
Seizure 
 
In clinical trials, uncommon cases of seizure were reported during treatment with aripiprazole. 



 63 

Therefore, aripiprazole should be used with caution in patients who have a history of seizure disorder 
or have conditions associated with seizures (see section 4.8). 
 
Elderly patients with dementia-related psychosis 
 
Increased mortality 
In three placebo-controlled trials (n = 938; mean age: 82.4 years; range: 56 to 99 years) of aripiprazole 
in elderly patients with psychosis associated with Alzheimer's disease, patients treated with 
aripiprazole were at increased risk of death compared to placebo. The rate of death in aripiprazole-
treated patients was 3.5 % compared to 1.7 % in the placebo group. Although the causes of deaths 
were varied, most of the deaths appeared to be either cardiovascular (e.g. heart failure, sudden death) 
or infectious (e.g. pneumonia) in nature (see section 4.8). 
 
Cerebrovascular adverse reactions 
In the same trials, cerebrovascular adverse reactions (e.g. stroke, transient ischaemic attack), including 
fatalities, were reported in patients (mean age: 84 years; range: 78 to 88 years). Overall, 1.3 % of 
aripiprazole-treated patients reported cerebrovascular adverse reactions compared with 0.6 % of 
placebo-treated patients in these trials. This difference was not statistically significant. However, in 
one of these trials, a fixed-dose trial, there was a significant dose response relationship for 
cerebrovascular adverse reactions in patients treated with aripiprazole (see section 4.8). 
 
Aripiprazole is not indicated for the treatment of patients with dementia-related psychosis. 
 
Hyperglycaemia and diabetes mellitus 
 
Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or 
death, has been reported in patients treated with atypical antipsychotics, including aripiprazole. Risk 
factors that may predispose patients to severe complications include obesity and family history of 
diabetes. In clinical trials with aripiprazole, there were no significant differences in the incidence rates 
of hyperglycaemia-related adverse reactions (including diabetes) or in abnormal glycaemia laboratory 
values compared to placebo. Precise risk estimates for hyperglycaemia-related adverse reactions in 
patients treated with aripiprazole and with other atypical antipsychotics are not available to allow 
direct comparisons. Patients treated with any antipsychotics, including aripiprazole, should be 
observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia and 
weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be 
monitored regularly for worsening of glucose control (see section 4.8). 
 
Hypersensitivity 
 
Hypersensitivity reactions, characterised by allergic symptoms, may occur with aripiprazole (see 
section 4.8). 
 
Weight gain 
 
Weight gain is commonly seen in schizophrenic and bipolar mania patients due to co-morbidities, use 
of antipsychotics known to cause weight gain, poorly managed life-style, and might lead to severe 
complications. Weight gain has been reported post-marketing among patients prescribed oral 
aripiprazole. When seen, it is usually in those with significant risk factors such as history of diabetes, 
thyroid disorder or pituitary adenoma. In clinical trials aripiprazole has not been shown to induce 
clinically relevant weight gain in adults (see section 5.1). In clinical trials of adolescent patients with 
bipolar mania, aripiprazole has been shown to be associated with weight gain after 4 weeks of 
treatment. Weight gain should be monitored in adolescent patients with bipolar mania. If weight gain 
is clinically significant, dose reduction should be considered (see section 4.8). 
 
Dysphagia 
 
Oesophageal dysmotility and aspiration have been associated with the use of antipsychotics, including 



 64 

aripiprazole. Aripiprazole should be used cautiously in patients at risk for aspiration pneumonia. 
 
Pathological gambling and other impulse control disorders 
 
Patients can experience increased urges, particularly for gambling, and the inability to control these 
urges while taking aripiprazole. Other urges, reported, include: increased sexual urges, compulsive 
shopping, binge or compulsive eating, and other impulsive and compulsive behaviours. It is important 
for prescribers to ask patients or their caregivers specifically about the development of new or 
increased gambling urges, sexual urges, compulsive shopping, binge or compulsive eating, or other 
urges while being treated with aripiprazole. It should be noted that impulse-control symptoms can be 
associated with the underlying disorder; however, in some cases, urges were reported to have stopped 
when the dose was reduced or the medication was discontinued. Impulse control disorders may result 
in harm to the patient and others if not recognised. Consider dose reduction or stopping the medication 
if a patient develops such urges while taking aripiprazole (see section 4.8). 
 
Sodium 
 
ABILIFY solution for injection contains sodium. This medicinal product contains less than 1 mmol 
sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’. 
 
Patients with attention deficit hyperactivity disorder (ADHD) comorbidity 
 
Despite the high comorbidity frequency of Bipolar I Disorder and ADHD, very limited safety data are 
available on concomitant use of aripiprazole and stimulants; therefore, extreme caution should be 
taken when these medicinal products are co-administered. 
 
Falls 
 
Aripiprazole may cause somnolence, postural hypotension, motor and sensory instability, which may 
lead to falls. Caution should be taken when treating patients at higher risk, and a lower starting dose 
should be considered (e.g., elderly or debilitated patients; see section 4.2). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No specific interaction studies have been performed with ABILIFY solution for injection. The 
information below is obtained from studies with oral aripiprazole. 
 
Due to its α1-adrenergic receptor antagonism, aripiprazole has the potential to enhance the effect of 
certain antihypertensive medicinal products. 
 
Given the primary CNS effects of aripiprazole, caution should be used when aripiprazole is 
administered in combination with alcohol or other CNS medicinal products with overlapping adverse 
reactions such as sedation (see section 4.8). 
 
If aripiprazole is administered concomitantly with medicinal products known to cause QT 
prolongation or electrolyte imbalance, caution should be used. 
 
Potential for other medicinal products to affect ABILIFY solution for injection 
 
The administration of lorazepam solution for injection had no effect on the pharmacokinetics of 
ABILIFY solution for injection when administered concomitantly. However, in a single-dose, 
intramuscular study of aripiprazole (dose 15 mg) in healthy subjects, administered simultaneously 
with intramuscular lorazepam (dose 2 mg), the intensity of sedation was greater with the combination 
as compared to that observed with aripiprazole alone. 
 
A gastric acid blocker, the H2 antagonist famotidine, reduces aripiprazole rate of absorption but this 
effect is deemed not clinically relevant. Aripiprazole is metabolised by multiple pathways involving 



 65 

the CYP2D6 and CYP3A4 enzymes but not CYP1A enzymes. Thus, no dosage adjustment is required 
for smokers. 
 
Quinidine and other CYP2D6 inhibitors 
In a clinical trial of oral aripiprazole in healthy subjects, a strong inhibitor of CYP2D6 (quinidine) 
increased aripiprazole AUC by 107 %, while Cmax was unchanged. The AUC and Cmax of dehydro-
aripiprazole, the active metabolite, decreased by 32 % and 47 %, respectively. Aripiprazole dose 
should be reduced to approximately one-half of its prescribed dose when concomitant administration 
of aripiprazole with quinidine occurs. Other strong inhibitors of CYP2D6, such as fluoxetine and 
paroxetine, may be expected to have similar effects and similar dose reductions should therefore be 
applied. 
 
Ketoconazole and other CYP3A4 inhibitors 
In a clinical trial of oral aripiprazole in healthy subjects, a strong inhibitor of CYP3A4 (ketoconazole) 
increased aripiprazole AUC and Cmax by 63 % and 37 %, respectively. The AUC and Cmax of dehydro-
aripiprazole increased by 77 % and 43 %, respectively. In CYP2D6 poor metabolisers, concomitant 
use of strong inhibitors of CYP3A4 may result in higher plasma concentrations of aripiprazole 
compared to that in CYP2D6 extensive metabolizers. When considering concomitant administration of 
ketoconazole or other strong CYP3A4 inhibitors with aripiprazole, potential benefits should outweigh 
the potential risks to the patient. When concomitant administration of ketoconazole with aripiprazole 
occurs, aripiprazole dose should be reduced to approximately one-half of its prescribed dose. Other 
strong inhibitors of CYP3A4, such as itraconazole and HIV protease inhibitors may be expected to 
have similar effects and similar dose reductions should therefore be applied (see section 4.2). Upon 
discontinuation of the CYP2D6 or CYP3A4 inhibitor, the dosage of aripiprazole should be increased 
to the level prior to the initiation of the concomitant therapy. When weak inhibitors of CYP3A4 (e.g. 
diltiazem) or CYP2D6 (e.g. escitalopram) are used concomitantly with aripiprazole, modest increases 
in plasma aripiprazole concentrations may be expected. 
 
Carbamazepine and other CYP3A4 inducers 
Following concomitant administration of carbamazepine, a strong inducer of CYP3A4, and oral 
aripiprazole to patients with schizophrenia or schizoaffective disorder, the geometric means of Cmax 
and AUC for aripiprazole were 68 % and 73 % lower, respectively, compared to when aripiprazole 
(30 mg) was administered alone. Similarly, for dehydro-aripiprazole the geometric means of Cmax and 
AUC after carbamazepine co-administration were 69 % and 71 % lower, respectively, than those 
following treatment with aripiprazole alone. Aripiprazole dose should be doubled when concomitant 
administration of aripiprazole occurs with carbamazepine. Concomitant administration of aripiprazole 
and other inducers of CYP3A4 (such as rifampicin, rifabutin, phenytoin, phenobarbital, primidone, 
efavirenz, nevirapine and St. John's Wort) may be expected to have similar effects and similar dose 
increases should therefore be applied. Upon discontinuation of strong CYP3A4 inducers, the dosage of 
aripiprazole should be reduced to the recommended dose. 
 
Valproate and lithium 
When either valproate or lithium was administered concomitantly with aripiprazole, there was no 
clinically significant change in aripiprazole concentrations and therefore no dose adjustment is 
necessary when either valproate or lithium is administered with aripiprazole. 
 
Potential for aripiprazole to affect other medicinal products 
 
The administration of ABILIFY solution for injection had no effect on the pharmacokinetics of 
lorazepam solution for injection when administered concomitantly. However, in a single-dose, 
intramuscular study of aripiprazole (dose 15 mg) in healthy subjects, administered simultaneously 
with intramuscular lorazepam (dose 2 mg), the orthostatic hypotension observed was greater with the 
combination as compared to that observed with lorazepam alone. 
 
In clinical studies, oral doses of 10 mg/day to 30 mg/day of aripiprazole had no significant effect on 
the metabolism of substrates of CYP2D6 (dextromethorphan/3-methoxymorphinan ratio), 
CYP2C9 (warfarin), CYP2C19 (omeprazole), and CYP3A4 (dextromethorphan). Additionally, 



 66 

aripiprazole and dehydro-aripiprazole did not show potential for altering CYP1A2-mediated 
metabolism in vitro. Thus, aripiprazole is unlikely to cause clinically important medicinal product 
interactions mediated by these enzymes. 
 
When aripiprazole was administered concomitantly with either valproate, lithium or lamotrigine, there 
was no clinically important change in valproate, lithium or lamotrigine concentrations. 
 
Serotonin syndrome 
Cases of serotonin syndrome have been reported in patients taking aripiprazole, and possible signs and 
symptoms for this condition can occur especially in cases of concomitant use with other serotonergic 
medicinal products, such as selective serotonin reuptake inhibitor/selective serotonin noradrenaline 
reuptake inhibitor (SSRI/SNRI), or with medicinal products that are known to increase aripiprazole 
concentrations (see section 4.8). 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no adequate and well-controlled trials of aripiprazole in pregnant women. Congenital 
anomalies have been reported; however, causal relationship with aripiprazole could not be established. 
Animal studies could not exclude potential developmental toxicity (see section 5.3). Patients must be 
advised to notify their physician if they become pregnant or intend to become pregnant during 
treatment with aripiprazole. Due to insufficient safety information in humans and concerns raised by 
animal reproductive studies, this medicinal product should not be used in pregnancy unless the 
expected benefit clearly justifies the potential risk to the foetus. 
 
Newborn infants exposed to antipsychotics (including aripiprazole) during the third trimester of 
pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that 
may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, 
hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborn 
infants should be monitored carefully (see section 4.8). 
 
Breast-feeding 
 
Aripiprazole/metabolites are excreted in human milk. A decision must be made whether to discontinue 
breast-feeding or to discontinue/abstain from aripiprazole therapy taking into account the benefit of 
breast-feeding for the child and the benefit of therapy for the woman. 
 
Fertility 
 
Aripiprazole did not impair fertility based on data from reproductive toxicity studies. 
 
4.7 Effects on ability to drive and use machines 
 
Aripiprazole has minor to moderate influence on the ability to drive and use machines due to potential 
nervous system and visual effects, such as sedation, somnolence, syncope, vision blurred, diplopia (see 
section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most commonly reported adverse reactions in placebo-controlled trials were nausea, dizziness and 
somnolence each occurring in more than 3 % of patients treated with aripiprazole solution for 
injection. 
 
Tabulated list of adverse reactions 



 67 

 
The incidences of the Adverse Drug Reactions (ADRs) associated with aripiprazole therapy are 
tabulated below. The table is based on adverse events reported during clinical trials and/or post-
marketing use. 
 
All ADRs are listed by system organ class and frequency; very common (≥ 1/10), common (≥ 1/100 to 
< 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000) and 
not known (cannot be estimated from the available data). Within each frequency grouping, adverse 
reactions are presented in order of decreasing seriousness. 
 
The frequency of adverse reactions reported during post-marketing use cannot be determined as they 
are derived from spontaneous reports. Consequently, the frequency of these adverse events is qualified 
as "not known". 
 
 Common Uncommon Not known 

 
Blood and 
lymphatic system 
disorders 

  Leukopenia 
Neutropenia 
Thrombocytopenia 

Immune system 
disorders 

  Allergic reaction (e.g. 
anaphylactic reaction, 
angioedema including swollen 
tongue, tongue oedema, face 
oedema, pruritus allergic, or 
urticaria) 

Endocrine 
disorders 

 Hyperprolactinaemia Diabetic hyperosmolar coma 
Diabetic ketoacidosis 

Metabolism and 
nutrition disorders 

Diabetes mellitus Hyperglycaemia Hyponatremia 
Anorexia 

Psychiatric 
disorders 

Insomnia 
Anxiety 
Restlessness 

Depression 
Hypersexuality 

Suicide attempt, suicidal ideation 
and completed suicide (see 
section 4.4) 
Pathological gambling 
Impulse-control disorder 
Binge eating 
Compulsive shopping 
Poriomania 
Aggression 
Agitation 
Nervousness  

Nervous system 
disorders 

Akathisia 
Extrapyramidal 
disorder 
Tremor 
Headache 
Sedation 
Somnolence 
Dizziness 

Tardive dyskinesia 
Dystonia 
Restless legs 
syndrome 
 

Neuroleptic Malignant Syndrome 
Grand mal convulsion 
Serotonin syndrome 
Speech disorder 
 

Eye disorders Vision blurred Diplopia 
Photophobia 

Oculogyric crisis 

Cardiac disorders  Tachycardia 
 

Sudden death unexplained  
Torsades de pointes 
Ventricular arrhythmia 
Cardiac arrest 
Bradycardia 

Vascular disorders  Orthostatic 
hypotension 

Venous thromboembolism 
(including pulmonary embolism 



 68 

 Common Uncommon Not known 
 
and deep vein thrombosis) 
Hypertension 
Syncope 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Hiccups Aspiration pneumonia 
Laryngospasm 
Oropharyngeal spasm 
 

Gastrointestinal 
disorders 

Constipation 
Dyspepsia 
Nausea 
Salivary 
hypersecretion 
Vomiting 

Mouth dry Pancreatitis 
Dysphagia 
Diarrhoea 
Abdominal discomfort 
Stomach discomfort 
 

Hepatobiliary 
disorders 

  Hepatic failure 
Hepatitis 
Jaundice 

Skin and 
subcutaneous tissue 
disorders 

  Rash 
Photosensitivity reaction 
Alopecia 
Hyperhidrosis 
Drug Reaction with Eosinophilia 
and Systemic Symptoms 
(DRESS) 

Musculoskeletal 
and connective 
tissue disorders 

  Rhabdomyolysis 
Myalgia 
Stiffness 

Renal and urinary 
disorders 

  Urinary incontinence 
Urinary retention 

Pregnancy, 
puerperium and 
perinatal conditions 

  Drug withdrawal syndrome 
neonatal (see section 4.6) 

Reproductive 
system and breast 
disorders 

  Priapism 

General disorders 
and administration 
site conditions 

Fatigue 
 

 Temperature regulation disorder 
(e.g. hypothermia, pyrexia) 
Chest pain 
Peripheral oedema 

Investigations  Diastolic blood 
pressure increased 

Weight decreased 
Weight gain 
Alanine Aminotransferase 
increased 
Aspartate Aminotransferase 
increased 
Gamma-glutamyltransferase 
increased 
Alkaline phosphatase increased 
QT prolonged 
Blood glucose increased 
Glycosylated haemoglobin 
increased 
Blood glucose fluctuation 
Creatine phosphokinase increased 

 
Description of selected adverse reactions 



 69 

 
Extrapyramidal symptoms (EPS) 
Schizophrenia: in a long-term 52-week controlled trial, aripiprazole-treated patients had an overall-
lower incidence (25.8 %) of EPS including Parkinsonism, akathisia, dystonia and dyskinesia compared 
with those treated with haloperidol (57.3 %). In a long-term 26-week placebo-controlled trial, the 
incidence of EPS was 19 % for aripiprazole-treated patients and 13.1 % for placebo-treated patients. In 
another long-term 26-week controlled trial, the incidence of EPS was 14.8 % for aripiprazole-treated 
patients and 15.1 % for olanzapine-treated patients. 
 
Manic episodes in Bipolar I Disorder: in a 12-week controlled trial, the incidence of EPS was 23.5 % 
for aripiprazole-treated patients and 53.3 % for haloperidol-treated patients. In another 12-week trial, 
the incidence of EPS was 26.6 % for patients treated with aripiprazole and 17.6 % for those treated 
with lithium. In the long-term 26-week maintenance phase of a placebo-controlled trial, the incidence 
of EPS was 18.2 % for aripiprazole-treated patients and 15.7 % for placebo-treated patients. 
 
Akathisia 
In placebo-controlled trials, the incidence of akathisia in bipolar patients was 12.1 % with aripiprazole 
and 3.2 % with placebo. In schizophrenia 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 muscle groups, may occur in 
susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of 
the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty 
breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur 
more frequently and with greater severity with high potency and at higher doses of first generation 
antipsychotic medicinal products. An elevated risk of acute dystonia is observed in males and younger 
age groups. 
 
Prolactin 
In clinical trials for the approved indications and post-marketing, both increase and decrease in serum 
prolactin as compared to baseline was observed with aripiprazole (section 5.1). 
 
Laboratory parameters 
Comparisons between aripiprazole and placebo in the proportions of patients experiencing potentially 
clinically significant changes in routine laboratory and lipid parameters (see section 5.1) revealed no 
medically important differences. Elevations of CPK (Creatine Phosphokinase), generally transient and 
asymptomatic, were observed in 3.5 % of aripiprazole treated patients as compared to 2.0 % of 
patients who received placebo. 
 
Pathological gambling and other impulse control disorders 
Pathological gambling, hypersexuality, compulsive shopping and binge or compulsive eating can 
occur in patients treated with aripiprazole (see section 4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No cases of overdose associated with adverse reactions were reported in clinical studies with 
ABILIFY solution for injection. Care must be taken to avoid inadvertent injection of this medicinal 
product into a blood vessel. Following any confirmed or suspected accidental overdose/inadvertent 
intravenous administration, close observation of the patient is needed and if any potentially medically 
serious sign or symptom develops, monitoring, which should include continuous electrocardiographic 

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 70 

monitoring, is required. The medical supervision and monitoring should continue until the patient 
recovers. 
 
Signs and symptoms 
 
In clinical trials and post-marketing experience, accidental or intentional acute overdose of 
aripiprazole alone was identified in adult patients with reported estimated doses up to 1,260 mg with 
no fatalities. The potentially medically important signs and symptoms observed included lethargy, 
increased blood pressure, somnolence, tachycardia, nausea, vomiting and diarrhoea. In addition, 
reports of accidental overdose with aripiprazole alone (up to 195 mg) in children have been received 
with no fatalities. The potentially medically serious signs and symptoms reported included 
somnolence, transient loss of consciousness and extrapyramidal symptoms. 
 
Management of overdose 
 
Management of overdose should concentrate on supportive therapy, maintaining an adequate airway, 
oxygenation and ventilation, and management of symptoms. The possibility of multiple medicinal 
product involvement should be considered. Therefore cardiovascular monitoring should be started 
immediately and should include continuous electrocardiographic monitoring to detect possible 
arrhythmias. Following any confirmed or suspected overdose with aripiprazole, close medical 
supervision and monitoring should continue until the patient recovers. 
 
Activated charcoal (50 g), administered one hour after aripiprazole, decreased aripiprazole Cmax by 
about 41 % and AUC by about 51 %, suggesting that charcoal may be effective in the treatment of 
overdose. 
 
Haemodialysis 
 
Although there is no information on the effect of haemodialysis in treating an overdose with 
aripiprazole, haemodialysis is unlikely to be useful in overdose management since aripiprazole is 
highly bound to plasma proteins. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Psycholeptics, other antipsychotics, ATC code: N05AX12 
 
Mechanism of action 
 
It has been proposed that aripiprazole’s efficacy in schizophrenia and Bipolar I Disorder is mediated 
through a combination of partial agonism at dopamine D2 and serotonin 5-HT1A receptors and 
antagonism of serotonin 5-HT2A receptors. Aripiprazole exhibited antagonist properties in animal 
models of dopaminergic hyperactivity and agonist properties in animal models of dopaminergic 
hypoactivity. Aripiprazole exhibited high binding affinity in vitro for dopamine D2 and D3, serotonin 
5-HT1A and 5-HT2A receptors and moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, 
alpha-1 adrenergic and histamine H1 receptors. Aripiprazole also exhibited moderate binding affinity 
for the serotonin reuptake site and no appreciable affinity for muscarinic receptors. Interaction with 
receptors other than dopamine and serotonin subtypes may explain some of the other clinical effects of 
aripiprazole. 
 
Aripiprazole doses ranging from 0.5 mg to 30 mg administered once a day to healthy subjects for 
2 weeks produced a dose-dependent reduction in the binding of 11C-raclopride, a D2/D3 receptor 
ligand, to the caudate and putamen detected by positron emission tomography. 
 
Clinical efficacy and safety 



 71 

 
Agitation in schizophrenia and Bipolar I Disorder with ABILIFY solution for injection 
In two short- term (24-hour) placebo-controlled trials involving 554 schizophrenic adult patients 
presenting with agitation and disturbed behaviours, ABILIFYsolution for injection was associated 
with statistically significant greater improvements in agitation/behavioural symptoms compared to 
placebo and was similar to haloperidol. 
 
In one short-term (24-hour) placebo-controlled trial involving 291 patients with bipolar disorder 
presenting with agitation and disturbed behaviours, ABILIFY solution for injection was associated 
with statistically significant greater improvements in agitation/behavioural symptoms compared to 
placebo and was similar to the reference arm lorazepam. The observed mean improvement from 
baseline on the PANSS Excitement Component score at the primary 2-hour endpoint was 5.8 for 
placebo, 9.6 for lorazepam, and 8.7 for ABILIFY solution for injection. In subpopulation analyses on 
patients with mixed episodes or on patients with severe agitation, a similar pattern of efficacy to the 
overall population was observed but statistical significance could not be established due to a reduced 
sample size. 
 
Schizophrenia with oral aripiprazole 
In three short-term (4 to 6 weeks) placebo-controlled trials involving 1,228 schizophrenic adult 
patients, presenting with positive or negative symptoms, oral aripiprazole was associated with 
statistically significantly greater improvements in psychotic symptoms compared to placebo. 
 
Aripiprazole is effective in maintaining the clinical improvement during continuation therapy in adult 
patients who have shown an initial treatment response. In a haloperidol-controlled trial, the proportion 
of responder patients maintaining response to medicinal product at 52-weeks was similar in both 
groups (oral aripiprazole 77 % and haloperidol 73 %). The overall completion rate was significantly 
higher for patients on oral aripiprazole (43 %) than for oral haloperidol (30 %). Actual scores in rating 
scales used as secondary endpoints, including PANSS and the Montgomery-Åsberg Depression Rating 
Scale (MADRS) showed a significant improvement over haloperidol. 
 
In a 26-week, placebo-controlled trial in adult stabilised patients with chronic schizophrenia, oral 
aripiprazole had significantly greater reduction in relapse rate, 34 % in oral aripiprazole group and 
57 % in placebo. 
 
Weight gain 
In clinical trials oral aripiprazole has not been shown to induce clinically relevant weight gain. In a 
26-week, olanzapine-controlled, double-blind, multi-national study of schizophrenia which included 
314 adult patients and where the primary endpoint was weight gain, significantly less patients had at 
least 7 % weight gain over baseline (i.e. a gain of at least 5.6 kg for a mean baseline weight of 
~80.5 kg) on oral aripiprazole (n = 18, or 13 % of evaluable patients), compared to oral olanzapine 
(n = 45, or 33 % of evaluable patients). 
 
Lipid parameters 
In a pooled analysis on lipid parameters from placebo controlled clinical trials in adults, aripiprazole 
has not been shown to induce clinically relevant alterations in levels of total cholesterol, triglycerides, 
High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL). 
 
Prolactin 
Prolactin levels were evaluated in all trials of all doses of aripiprazole (n = 28,242). The incidence of 
hyperprolactinaemia or increased serum prolactin in patients treated with aripiprazole (0.3 %) was 
similar to that of placebo (0.2 %). For patients receiving aripiprazole, the median time to onset was 
42 days and median duration was 34 days. 
 
The incidence of hypoprolactinaemia or decreased serum prolactin in patients treated with aripiprazole 
was 0.4 %, compared with 0.02 % for patients treated with placebo. For patients receiving 
aripiprazole, the median time to onset was 30 days and median duration was 194 days. 
 



 72 

Manic episodes in Bipolar I Disorder with oral aripiprazole 
In two 3-week, flexible-dose, placebo-controlled monotherapy trials involving patients with a manic or 
mixed episode of Bipolar I Disorder, aripiprazole demonstrated superior efficacy to placebo in 
reduction of manic symptoms over 3 weeks. These trials included patients with or without psychotic 
features and with or without a rapid-cycling course. 
 
In one 3-week, fixed-dose, placebo-controlled monotherapy trial involving patients with a manic or 
mixed episode of Bipolar I Disorder, aripiprazole failed to demonstrate superior efficacy to placebo. 
 
In two 12-week, placebo- and active-controlled monotherapy trials in patients with a manic or mixed 
episode of Bipolar I Disorder, with or without psychotic features, aripiprazole demonstrated superior 
efficacy to placebo at week 3 and a maintenance of effect comparable to lithium or haloperidol at 
week 12. Aripiprazole also demonstrated a comparable proportion of patients in symptomatic 
remission from mania as lithium or haloperidol at week 12. 
 
In a 6-week, placebo-controlled trial involving patients with a manic or mixed episode of Bipolar I 
Disorder, with or without psychotic features, who were partially non-responsive to lithium or 
valproate monotherapy for 2 weeks at therapeutic serum levels, the addition of aripiprazole as 
adjunctive therapy resulted in superior efficacy in reduction of manic symptoms than lithium or 
valproate monotherapy. 
 
In a 26-week, placebo-controlled trial, followed by a 74-week extension, in manic patients who 
achieved remission on aripiprazole during a stabilization phase prior to randomisation, aripiprazole 
demonstrated superiority over placebo in preventing bipolar recurrence, primarily in preventing 
recurrence into mania but failed to demonstrate superiority over placebo in preventing recurrence into 
depression. 
 
In a 52-week, placebo-controlled trial, in patients with a current manic or mixed episode of Bipolar I 
Disorder who achieved sustained remission (Young Mania Rating Scale [YMRS] and MADRS with 
total scores ≤ 12) on aripiprazole (10 mg/day to 30 mg/day) adjunctive to lithium or valproate for 
12 consecutive weeks, adjunctive aripiprazole demonstrated superiority over placebo with a 46 % 
decreased risk (hazard ratio of 0.54) in preventing bipolar recurrence and a 65 % decreased risk 
(hazard ratio of 0.35) in preventing recurrence into mania over adjunctive placebo but failed to 
demonstrate superiority over placebo in preventing recurrence into depression. Adjunctive aripiprazole 
demonstrated superiority over placebo on the secondary outcome measure in Clinical Global 
Impression - Bipolar version (CGI-BP) Severity of Illness (SOI; mania) scores. In this trial, patients 
were assigned by investigators with either open-label lithium or valproate monotherapy to determine 
partial non-response. Patients were stabilised for at least 12 consecutive weeks with the combination 
of aripiprazole and the same mood stabilizer. Stabilized patients were then randomised to continue the 
same mood stabilizer with double-blind aripiprazole or placebo. Four mood stabilizer subgroups were 
assessed in the randomised phase: aripiprazole + lithium; aripiprazole + valproate; placebo + lithium; 
placebo + valproate. The Kaplan-Meier rates for recurrence to any mood episode for the adjunctive 
treatment arm were 16 % in aripiprazole + lithium and 18 % in aripiprazole + valproate compared to 
45 % in placebo + lithium and 19 % in placebo + valproate. 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
ABILIFY in one or more subsets of the paediatric population in the treatment of schizophrenia and in 
the treatment of bipolar affective disorder (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Aripiprazole administered intramuscularly as a single-dose to healthy subjects is well absorbed and 
has an absolute bioavailability of 100 %. The aripiprazole AUC in the first 2 hours after an 
intramuscular injection was 90 % greater than the AUC after the same dose as a tablet; systemic 
exposure was generally similar between the 2 formulations. In 2 studies in healthy subjects the median 
times to the peak plasma concentrations were 1 and 3 hours after dosing. 



 73 

 
Distribution 
 
Based on results from trials with oral administration of aripiprazole, aripiprazole is widely distributed 
throughout the body with an apparent volume of distribution of 4.9 L/kg, indicating extensive 
extravascular distribution. At therapeutic concentrations, aripiprazole and dehydro-aripiprazole are 
greater than 99 % bound to serum proteins, binding primarily to albumin. 
 
Biotransformation 
 
Aripiprazole is extensively metabolised by the liver primarily by three biotransformation pathways: 
dehydrogenation, hydroxylation, and N-dealkylation. Based on in vitro studies, CYP3A4 and CYP2D6 
enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is 
catalysed by CYP3A4. Aripiprazole is the predominant medicinal product moiety in systemic 
circulation. At steady state, dehydro-aripiprazole, the active metabolite, represents about 40 % of 
aripiprazole AUC in plasma. 
 
Elimination 
 
The mean elimination half-lives for aripiprazole are approximately 75 hours in extensive metabolisers 
of CYP2D6 and approximately 146 hours in poor metabolisers of CYP2D6. 
 
The total body clearance of aripiprazole is 0.7 mL/min/kg, which is primarily hepatic. 
 
Following a single oral dose of [14C]-labelled aripiprazole, approximately 27 % of the administered 
radioactivity was recovered in the urine and approximately 60 % in the faeces. Less than 1 % of 
unchanged aripiprazole was excreted in the urine and approximately 18 % was recovered unchanged 
in the faeces. 
 
Pharmacokinetics in special patient groups 
 
Elderly 
There are no differences in the pharmacokinetics of aripiprazole between healthy elderly and younger 
adult subjects, nor is there any detectable effect of age in a population pharmacokinetic analysis in 
schizophrenic patients. 
 
Gender 
There are no differences in the pharmacokinetics of aripiprazole between healthy male and female 
subjects nor is there any detectable effect of gender in a population pharmacokinetic analysis in 
schizophrenic patients. 
 
Smoking 
Population pharmacokinetic evaluation of oral aripiprazole has revealed no evidence of clinically 
relevant effects from smoking on the pharmacokinetics of aripiprazole. 
 
Race 
Population pharmacokinetic evaluation showed no evidence of race-related differences on the 
pharmacokinetics of aripiprazole. 
 
Renal impairment 
The pharmacokinetic characteristics of aripiprazole and dehydro-aripiprazole were found to be similar 
in patients with severe renal disease compared to young healthy subjects. 
 
Hepatic impairment 
A single-dose study in subjects with varying degrees of liver cirrhosis (Child-Pugh Classes A, B, 
and C) did not reveal a significant effect of hepatic impairment on the pharmacokinetics of 
aripiprazole and dehydro-aripiprazole, but the study included only 3 patients with Class C liver 



 74 

cirrhosis, which is insufficient to draw conclusions on their metabolic capacity. 
 
5.3 Preclinical safety data 
 
Administration of ABILIFY solution for injection was well tolerated and produced no direct target 
organ toxicity in rats or monkeys after repeated dosing at systemic exposures (AUC) that were 15 and 
5 times, respectively, human exposure at the maximum recommended human dose of 30 mg 
intramuscular. In intravenous reproductive toxicity studies, no new safety concerns were observed at 
maternal exposures up to 15 (rat) and 29 (rabbit) times human exposure at 30 mg. 
 
Non-clinical data reveal no special hazard for humans based on conventional oral aripiprazole studies 
of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to 
reproduction and development. 
 
Toxicologically significant effects were observed only at doses or exposures that were sufficiently in 
excess of the maximum human dose or exposure, indicating that these effects were limited or of no 
relevance to clinical use. These included: dose-dependent adrenocortical toxicity (lipofuscin pigment 
accumulation and/or parenchymal cell loss) in rats after 104 weeks at 20 mg/kg/day to 60 mg/kg/day 
(3 to 10 times the mean steady-state AUC at the maximum recommended human dose) and increased 
adrenocortical carcinomas and combined adrenocortical adenomas/carcinomas in female rats at 
60 mg/kg/day (10 times the mean steady-state AUC at the maximum recommended human dose). The 
highest nontumorigenic exposure in female rats was 7 times the human exposure at the recommended 
dose. 
 
An additional finding was cholelithiasis as a consequence of precipitation of sulphate conjugates of 
hydroxy metabolites of aripiprazole in the bile of monkeys after repeated oral dosing at 25 mg/kg/day 
to 125 mg/kg/day (1 to 3 times the mean steady-state AUC at the maximum recommended clinical 
dose or 16 to 81 times the maximum recommended human dose based on mg/m2). However, the 
concentrations of the sulphate conjugates of hydroxy aripiprazole in human bile at the highest dose 
proposed, 30 mg per day, were no more than 6 % of the bile concentrations found in the monkeys in 
the 39-week study and are well below (6 %) their limits of in vitro solubility. 
 
In repeat-dose studies in juvenile rats and dogs, the toxicity profile of aripiprazole was comparable to 
that observed in adult animals, and there was no evidence of neurotoxicity or adverse reactions on 
development. 
 
Based on results of a full range of standard genotoxicity tests, aripiprazole was considered non-
genotoxic. Aripiprazole did not impair fertility in reproductive toxicity studies. Developmental 
toxicity, including dose-dependent delayed foetal ossification and possible teratogenic effects, were 
observed in rats at doses resulting in subtherapeutic exposures (based on AUC) and in rabbits at doses 
resulting in exposures 3 and 11 times the mean steady-state AUC at the maximum recommended 
clinical dose. Maternal toxicity occurred at doses similar to those eliciting developmental toxicity. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sulfobutylether β-cyclodextrin (SBECD) 
Tartaric acid 
Sodium hydroxide 
Water for injections 
 
6.2 Incompatibilities 
 
Not applicable. 
 



 75 

6.3 Shelf life 
 
18 months 
After opening: use product immediately. 
 
6.4 Special precautions for storage 
 
Keep the vial in the outer carton in order to protect from light. 
 
For storage conditions after first opening of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Each carton contains one single-use type I glass vial with a rubber butyl stopper and a "tear-off" 
aluminium seal. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/036 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 04 June 2004 
Date of latest renewal: 04 June 2009 
 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu/


 76 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS RESPONSIBLE FOR BATCH 
RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 
 



 77 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
Elaiapharm 
2881 Route des Crêtes, Z.I. Les Bouilides-Sophia Antipolis, 
06560 Valbonne 
France 
 
Zambon S.p.A. 
Via della Chimica, 9 
I-36100 Vicenza(VI) 
Italy 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 



 78 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



 79 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 80 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 5 mg tablets 
aripiprazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 5 mg of aripiprazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablets 
 
14 × 1 tablets 
28 × 1 tablets 
49 × 1 tablets 
56 × 1 tablets 
98 × 1 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 



 81 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/001 (5 mg, 14 × 1 tablets) 
EU/1/04/276/002 (5 mg, 28 × 1 tablets) 
EU/1/04/276/003 (5 mg, 49 × 1 tablets) 
EU/1/04/276/004 (5 mg, 56 × 1 tablets) 
EU/1/04/276/005 (5 mg, 98 × 1 tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
abilify 5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 82 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 5 mg tablets 
aripiprazole 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



 83 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 10 mg tablets 
aripiprazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 10 mg of aripiprazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablets 
 
14 × 1 tablets 
28 × 1 tablets 
49 × 1 tablets 
56 × 1 tablets 
98 × 1 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 



 84 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/006 (10 mg, 14 × 1 tablets) 
EU/1/04/276/007 (10 mg, 28 × 1 tablets) 
EU/1/04/276/008 (10 mg, 49 × 1 tablets) 
EU/1/04/276/009 (10 mg, 56 × 1 tablets) 
EU/1/04/276/010 (10 mg, 98 × 1 tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
abilify 10 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 85 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 10 mg tablets 
aripiprazole 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



 86 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 15 mg tablets 
aripiprazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 15 mg of aripiprazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablets 
 
14 × 1 tablets 
28 × 1 tablets 
49 × 1 tablets 
56 × 1 tablets 
98 × 1 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 



 87 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/011 (15 mg, 14 × 1 tablets) 
EU/1/04/276/012 (15 mg, 28 × 1 tablets) 
EU/1/04/276/013 (15 mg, 49 × 1 tablets) 
EU/1/04/276/014 (15 mg, 56 × 1 tablets) 
EU/1/04/276/015 (15 mg, 98 × 1 tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
abilify 15 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 88 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 15 mg tablets 
aripiprazole 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



 89 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 30 mg tablets 
aripiprazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 30 mg of aripiprazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains: lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Tablets 
 
14 × 1 tablets 
28 × 1 tablets 
49 × 1 tablets 
56 × 1 tablets 
98 × 1 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 



 90 

 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/016 (30 mg, 14 × 1 tablets) 
EU/1/04/276/017 (30 mg, 28 × 1 tablets) 
EU/1/04/276/018 (30 mg, 49 × 1 tablets) 
EU/1/04/276/019 (30 mg, 56 × 1 tablets) 
EU/1/04/276/020 (30 mg, 98 × 1 tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
abilify 30 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 91 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 30 mg tablets 
aripiprazole 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



 92 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 10 mg orodispersible tablets 
aripiprazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 10 mg of aripiprazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains aspartame and lactose. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Orodispersible tablets 
 
14 × 1 orodispersible tablets 
28 × 1 orodispersible tablets 
49 × 1 orodispersible tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 

 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 



 93 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/024 (10 mg, 14 × 1 orodispersible tablets) 
EU/1/04/276/025 (10 mg, 28 × 1 orodispersible tablets) 
EU/1/04/276/026 (10 mg, 49 × 1 orodispersible tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
abilify 10 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



 94 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 10 mg orodispersible tablets 
aripiprazole 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



 95 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 15 mg orodispersible tablets 
aripiprazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 15 mg of aripiprazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains aspartame and lactose. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Orodispersible tablets 
 
14 × 1 orodispersible tablets 
28 × 1 orodispersible tablets 
49 × 1 orodispersible tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 

 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 



 96 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/027 (15 mg, 14 × 1 orodispersible tablets) 
EU/1/04/276/028 (15 mg, 28 × 1 orodispersible tablets) 
EU/1/04/276/029 (15 mg, 49 × 1 orodispersible tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
abilify 15 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 97 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 15 mg orodispersible tablets 
aripiprazole 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



 98 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 30 mg orodispersible tablets 
aripiprazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 30 mg of aripiprazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains aspartame and lactose. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Orodispersible tablets 
 
14 × 1 orodispersible tablets 
28 × 1 orodispersible tablets 
49 × 1 orodispersible tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 

 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 



 99 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from moisture. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/030 (30 mg, 14 × 1 orodispersible tablets) 
EU/1/04/276/031 (30 mg, 28 × 1 orodispersible tablets) 
EU/1/04/276/032 (30 mg, 49 × 1 orodispersible tablets) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
abilify 30 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 100 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTERS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 30 mg orodispersible tablets 
aripiprazole 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 



 101 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 
 
OUTER CARTON AND BOTTLE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 1 mg/mL oral solution 
aripiprazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL contains 1 mg of aripiprazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains fructose, sucrose, E218, and E216. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Oral solution 
 
50 mL oral solution 
150 mL oral solution 
480 mL oral solution 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
Use within 6 months after first opening. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



 102 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Outer carton: 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/033 - 50 mL bottle 
EU/1/04/276/034 - 150 mL bottle 
EU/1/04/276/035 - 480 mL bottle 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Outer carton: abilify 1 mg/mL 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 103 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ABILIFY 7.5 mg/mL solution for injection 
aripiprazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each mL contains 7.5 mg of aripiprazole. A vial provides 9.75 mg in 1.3 mL. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains sulfobutylether b-cyclodextrin, tartaric acid, sodium hydroxide, and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
 
1 vial 
9.75 mg / 1.3 mL 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Intramuscular use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the vial in the outer carton in order to protect from light. 
 
 



 104 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/276/036 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



 105 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
ABILIFY 7.5 mg/mL solution for injection 
aripiprazole 
 
IM use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
9.75 mg / 1.3 mL 
 
 
6. OTHER 
 



 106 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 107 

Package leaflet: Information for the user 
 

ABILIFY 5 mg tablets 
ABILIFY 10 mg tablets 
ABILIFY 15 mg tablets 
ABILIFY 30 mg tablets 

 
aripiprazole 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What ABILIFY is and what it is used for 
2. What you need to know before you take ABILIFY 
3. How to take ABILIFY 
4. Possible side effects 
5 How to store ABILIFY 
6. Contents of the pack and other information 
 
 
1. What ABILIFY is and what it is used for 
 
ABILIFY contains the active substance aripiprazole and belong to a group of medicines called 
antipsychotics. It is used to treat adults and adolescents aged 15 years and older who suffer from a 
disease characterised by symptoms such as hearing, seeing or sensing things which are not there, 
suspiciousness, mistaken beliefs, incoherent speech and behaviour and emotional flatness. People with 
this condition may also feel depressed, guilty, anxious or tense. 
 
ABILIFY is used to treat adults and adolescents aged 13 years and older who suffer from a condition 
with symptoms such as feeling "high", having excessive amounts of energy, needing much less sleep 
than usual, talking very quickly with racing ideas and sometimes severe irritability. In adults it also 
prevents this condition from returning in patients who have responded to the treatment with ABILIFY. 
 
 
2. What you need to know before you take ABILIFY 
 
Do not take ABILIFY 
• if you are allergic to aripiprazole or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
Talk to your doctor before taking ABILIFY. 
 
Suicidal thoughts and behaviours have been reported during aripiprazole treatment. Tell your doctor 
immediately if you are having any thoughts or feelings about hurting yourself. 
 
Before treatment with ABILIFY, tell your doctor if you suffer from 
• high blood sugar (characterised by symptoms such as excessive thirst, passing of large amounts 

of urine, increase in appetite and feeling weak) or family history of diabetes 
• fits (seizures) since your doctor may want to monitor you more closely 



 108 

• involuntary, irregular muscle movements, especially in the face 
• cardiovascular diseases (diseases of the heart and circulation), family history of cardiovascular 

disease, stroke or "mini" stroke, abnormal blood pressure 
• blood clots, or family history of blood clots, as antipsychotics have been associated with 

formation of blood clots 
• past experience with excessive gambling 
 
If you notice you are gaining weight, develop unusual movements, experience somnolence that 
interferes with normal daily activities, any difficulty in swallowing or allergic symptoms, please tell 
your doctor. 
 
If you are an elderly patient suffering from dementia (loss of memory and other mental abilities), you 
or your carer/relative should tell your doctor if you have ever had a stroke or "mini" stroke. 
 
Tell your doctor immediately if you are having any thoughts or feelings about hurting yourself. 
Suicidal thoughts and behaviours have been reported during aripiprazole treatment. 
 
Tell your doctor immediately if you suffer from muscle stiffness or inflexibility with high fever, 
sweating, altered mental status, or very rapid or irregular heartbeat. 
 
Tell your doctor if you or your family/carer notices that you are developing urges or cravings to 
behave in ways that are unusual for you and you cannot resist the impulse, drive or temptation to carry 
out certain activities that could harm yourself or others. These are called impulse control disorders and 
can include behaviours such as addictive gambling, excessive eating or spending, an abnormally high 
sex drive or preoccupation with an increase in sexual thoughts or feelings. 
Your doctor may need to adjust or stop your dose. 
 
Aripiprazole may cause sleepiness, fall in blood pressure when standing up, dizziness and changes in 
your ability to move and balance, which may lead to falls. Caution should be taken, particularly if you 
are an elderly patient or have some debility. 
 
Children and adolescents 
Do not use this medicine in children and adolescents under 13 years of age. It is not known if it is safe 
and effective in these patients. 
 
Other medicines and ABILIFY 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without a prescription. 
 
Blood pressure-lowering medicines: ABILIFY may increase the effect of medicines used to lower the 
blood pressure. Be sure to tell your doctor if you take a medicine to keep your blood pressure under 
control. 
 
Taking ABILIFY with some medicines may mean the doctor will need to change your dose of 
ABILIFY or the other medicines. It is especially important to mention the following to your doctor: 
 
• medicines to correct heart rhythm (such as quinidine, amiodarone, flecainide) 
• antidepressants or herbal remedy used to treat depression and anxiety (such as fluoxetine, 

paroxetine, venlafaxine, St. John's Wort) 
• antifungal medicines (such as ketoconazole, itraconazole) 
• certain medicines to treat HIV infection (such as efavirenz, nevirapine, an protease inhibitors 

e.g. indinavir, ritonavir) 
• anticonvulsants used to treat epilepsy (such as carbamazepine, phenytoin, phenobarbital) 
• certain antibiotics used to treat tuberculosis (rifabutin, rifampicin) 
 
These medicines may increase the risk of side effects or reduce the effect of ABILIFY; if you get any 
unusual symptom taking any of these medicines together with ABILIFY you should see your doctor. 



 109 

 
Medicines that increase the level of serotonin are typically used in conditions including depression, 
generalised anxiety disorder, obsessive-compulsive disorder (OCD) and social phobia as well as 
migraine and pain: 
 
• triptans, tramadol and tryptophan used for conditions including depression, generalised anxiety 

disorder, obsessive compulsive disorder (OCD) and social phobia as well as migraine and pain 
• selective-serotonin-reuptake-inhibitors (SSRIs) (such as paroxetine and fluoxetine) used for 

depression, OCD, panic and anxiety 
• other anti-depressants (such as venlafaxine and tryptophan) used in major depression 
• tricyclic’s (such as clomipramine and amitriptyline) used for depressive illness 
• St John’s Wort (Hypericum perforatum) used as a herbal remedy for mild depression 
• pain killers (such as tramadol and pethidine) used for pain relief 
• triptans (such as sumatriptan and zolmitripitan) used for treating migraine 
 
These medicines may increase the risk of side effects; if you get any unusual symptom taking any of 
these medicines together with ABILIFY, you should see your doctor. 
 
ABILIFY with food, drink and alcohol 
This medicine can be taken regardless of meals. 
Alcohol should be avoided. 
 
Pregnancy, breast-feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 
The following symptoms may occur in newborn babies, of mothers that have used ABILIFY in the last 
trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, sleepiness, 
agitation, breathing problems, and difficulty in feeding. If your baby develops any of these symptoms 
you may need to contact your doctor. 
 
If you are taking ABILIFY, your doctor will discuss with you whether you should breast-feed 
considering the benefit to you of your therapy and the benefit to your baby of breast-feeding. You 
should not do both. Talk to your doctor about the best way to feed your baby if you are taking this 
medicine. 
 
Driving and using machines 
Dizziness and vision problems may occur during treatment with this medicine (see section 4). 
This should be considered in cases where full alertness is required, e.g. when driving a car or handling 
machines. 
 
ABILIFY contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
 
3. How to take ABILIFY 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
The recommended dose for adults is 15 mg once a day. However your doctor may prescribe a lower 
or higher dose to a maximum of 30 mg once a day. 
 
Use in children and adolescents 
This medicinal product may be started at a low dose with the oral solution (liquid) form. 
The dose may be gradually increased to the recommended dose for adolescents of 10 mg once a 

http://en.wikipedia.org/wiki/Major_depressive_disorder
http://en.wikipedia.org/wiki/Generalized_anxiety_disorder
http://en.wikipedia.org/wiki/Social_anxiety_disorder


 110 

day. However your doctor may prescribe a lower or higher dose to a maximum of 30 mg once a day. 
 
If you have the impression that the effect of ABILIFY is too strong or too weak, talk to your doctor or 
pharmacist. 
 
Try to take ABILIFY at the same time each day. It does not matter whether you take it with or 
without food. Always take the tablet with water and swallow it whole. 
 
Even if you feel better, do not alter or discontinue the daily dose of ABILIFY without first consulting 
your doctor. 
 
If you take more ABILIFY than you should 
If you realise you have taken more ABILIFY than your doctor has recommended (or if someone else 
has taken some of your ABILIFY), contact your doctor right away. If you cannot reach your doctor, go 
to the nearest hospital and take the pack with you. 
 
Patients who have taken too much aripiprazole have experienced the following symptoms: 
• rapid heartbeat, agitation/aggressiveness, problems with speech. 
• unusual movements (especially of the face or tongue) and reduced level of consciousness. 
 
Other symptoms may include: 
• acute confusion, seizures (epilepsy), coma, a combination of fever, faster breathing, sweating, 
• muscle stiffness, and drowsiness or sleepiness, slower breathing, choking, high or low blood 

pressure, abnormal rhythms of the heart. 
 
Contact your doctor or hospital immediately if you experience any of the above. 
 
If you forget to take ABILIFY 
If you miss a dose, take the missed dose as soon as you remember but do not take two doses in one 
day. 
 
If you stop taking ABILIFY 
Do not stop your treatment just because you feel better. It is important that you carry on taking 
ABILIFY for as long as your doctor has told you to. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Common side effects (may affect up to 1 in 10 people): 
 
• diabetes mellitus, 
• difficulty sleeping, 
• feeling anxious, 
• feeling restless and unable to keep still, difficulty sitting still, 
• akathisia (an uncomfortable feeling of inner restlessness and a compelling need to move 

constantly), 
• uncontrollable twitching, jerking or writhing movements, 
• trembling, 
• headache, 
• tiredness, 
• sleepiness, 
• light-headedness, 
• shaking and blurred vision, 



 111 

• decreased number of or difficulty making bowel movements, 
• indigestion, 
• feeling sick, 
• more saliva in mouth than normal, 
• vomiting, 
• feeling tired. 
 
Uncommon side effects (may affect up to 1 in 100 people): 
 
• increased blood levels of the hormone prolactin, 
• too much sugar in the blood, 
• depression, 
• altered or increased sexual interest, 
• uncontrollable movements of mouth, tongue and limbs (tardive dyskinesia), 
• muscle disorder causing twisting movements (dystonia), 
• restless legs, 
• double vision, 
• eye sensitivity to light, 
• fast heartbeat, 
• a fall in blood pressure on standing up which causes dizziness, light-headedness or fainting, 
• hiccups. 
 
The following side effects have been reported since the marketing of oral aripiprazole but the 
frequency for them to occur is not known: 
 
• low levels of white blood cells, 
• low levels of blood platelets, 
• allergic reaction (e.g. swelling in the mouth, tongue, face and throat, itching, hives), 
• onset or worsening of diabetes, ketoacidosis (ketones in the blood and urine) or coma, 
• high blood sugar, 
• not enough sodium in the blood, 
• loss of appetite (anorexia), 
• weight loss, 
• weight gain, 
• thoughts of suicide, suicide attempt and suicide, 
• feeling aggressive, 
• agitation, 
• nervousness, 
• combination of fever, muscle stiffness, faster breathing, sweating, reduced consciousness and 

sudden changes in blood pressure and heart rate, fainting (neuroleptic malignant syndrome), 
• seizure, 
• serotonin syndrome (a reaction which may cause feelings of great happiness, drowsiness, 

clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), 
• speech disorder, 
• fixation of the eyeballs in one position, 
• sudden unexplained death, 
• life-threatening irregular heartbeat, 
• heart attack, 
• slower heartbeat, 
• blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in 

the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in 
breathing (if you notice any of these symptoms, seek medical advice immediately), 

• high blood pressure, 
• fainting, 
• accidental inhalation of food with risk of pneumonia (lung infection), 
• spasm of the muscles around the voice box, 
• inflammation of the pancreas, 



 112 

• difficulty swallowing, 
• diarrhoea, 
• abdominal discomfort, 
• stomach discomfort, 
• liver failure, 
• inflammation of the liver, 
• yellowing of the skin and white part of eyes, 
• reports of abnormal liver tests values, 
• skin rash, 
• skin sensitivity to light, 
• baldness, 
• excessive sweating, 
• serious allergic reactions such as Drug Reaction with Eosinophilia and Systemic Symptoms 

(DRESS). DRESS appears initially as flu-like symptoms with a rash on the face and then with 
an extended rash, high temperature, enlarged lymph nodes, increased levels of liver enzymes 
seen in blood tests and an increase in a type of white blood cell (eosinophilia), 

• abnormal muscle breakdown which can lead to kidney problems, 
• muscle pain, 
• stiffness, 
• involuntary loss of urine (incontinence), 
• difficulty in passing urine, 
• withdrawal symptoms in newborn babies in case of exposure during pregnancy, 
• prolonged and/or painful erection, 
• difficulty controlling core body temperature or overheating, 
• chest pain, 
• swelling of hands, ankles or feet, 
• in blood tests: increased or fluctuating blood sugar, increased glycosylated haemoglobin. 
• Inability to resist the impulse, drive or temptation to perform an action that could be harmful to 

you or others, which may include: 
- strong impulse to gamble excessively despite serious personal or family consequences 
- altered or increased sexual interest and behaviour of significant concern to you or to 

others, for example, an increased sexual drive 
- uncontrollable excessive shopping 
- binge eating (eating large amounts of food in a short time period) or compulsive eating 

(eating more food than normal and more than is needed to satisfy your hunger) 
- a tendency to wander away. 
Tell your doctor if you experience any of these behaviours; he/she will discuss ways of 
managing or reducing the symptoms. 

 
In elderly patients with dementia, more fatal cases have been reported while taking aripiprazole. In 
addition, cases of stroke or "mini" stroke have been reported. 
 
Additional side effects in children and adolescents 
Adolescents aged 13 years and older experienced side effects that were similar in frequency and type 
to those in adults except that sleepiness, uncontrollable twitching or jerking movements, restlessness, 
and tiredness were very common (greater than 1 in 10 patients) and upper abdominal pain, dry mouth, 
increased heart rate, weight gain, increased appetite, muscle twitching, uncontrolled movements of the 
limbs, and feeling dizzy, especially when getting up from a lying or sitting position, were common 
(greater than 1 in 100 patients). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 113 

5. How to store ABILIFY 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the blister and on the carton after 
EXP. The expiry date refers to the last day of that month. 
 
Store in the original package in order to protect from moisture. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What ABILIFY contains 
• The active substance is aripiprazole. 
 Each tablet contains 5 mg of aripiprazole. 
 Each tablet contains 10 mg of aripiprazole. 
 Each tablet contains 15 mg of aripiprazole. 
 Each tablet contains 30 mg of aripiprazole. 
 
• The other ingredients are lactose monohydrate, maize starch, microcrystalline cellulose, 

hydroxypropylcellulose and magnesium stearate. 
Tablet coat 
ABILIFY 5 mg tablets:  Indigo carmine aluminium lake (E 132) 
ABILIFY 10 mg tablets:  Red iron oxide (E 172) 
ABILIFY 15 mg tablets:  Yellow iron oxide (E 172) 
ABILIFY 30 mg tablets:  Red iron oxide (E 172) 

 
What ABILIFY looks like and contents of the pack 
ABILIFY 5 mg tablets are rectangular and blue, marked with ‘A-007’ and ‘5’ on one side. 
ABILIFY 10 mg tablets are rectangular and pink, marked with ‘A-008’ and ‘10’ on one side. 
ABILIFY 15 mg tablets are round and yellow, marked with ‘A-009’ and ‘15’ on one side. 
ABILIFY 30 mg tablets are round and pink, marked with ‘A-011’ and ‘30’ on one side. 
 
ABILIFY tablets are supplied in perforated unit dose blisters packed in cartons containing 14 × 1, 
28 × 1, 49 × 1, 56 × 1, or 98 × 1 tablets. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
Manufacturer 
Elaiapharm 
2881 Route des Crêtes, Z.I. Les Bouilides-Sophia Antipolis, 
06560 Valbonne 
France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 



 114 

België/Belgique/Belgien 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Lietuva 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

България 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Luxembourg/Luxemburg 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Česká republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Magyarország 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Danmark 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Malta 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Deutschland 
Otsuka Pharma GmbH 
Tel: +49 (0) 69 1700 860 
 

Nederland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Eesti 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Norge 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Ελλάδα 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Österreich 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

España 
Otsuka Pharmaceutical, S.A. 
Tel: +34 93 550 01 00 
 

Polska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

France 
Otsuka Pharmaceutical France SAS 
Tél: +33 (0)1 47 08 00 00 
 

Portugal 
Lundbeck Portugal Lda 
Tel: +351 (0) 21 00 45 900 
 

Hrvatska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

România 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Ireland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Slovenija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Ísland 
Vistor hf. 
Sími: +354 (0) 535 7000 
 

Slovenská republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Italia 
Otsuka Pharmaceutical Italy S.r.l. 
Tel: +39 (0) 2 0063 2710 
 

Suomi/Finland 
Otsuka Pharma Scandinavia AB 
Puh/Tel: +46 (0) 8 545 286 60 
 

Κύπρος 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Sverige 
Otsuka Pharma Scandinavia AB 
Tel: +46 (0) 8 545 286 60 
 



 115 

Latvija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

United Kingdom 
Otsuka Pharmaceuticals (UK) Ltd. 
Tel: +44 (0) 203 747 5300 
 

 
This leaflet was last revised in {MM/YYYY} 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

http://www.ema.europa.eu/


 116 

Package leaflet: Information for the user 
 

ABILIFY 10 mg orodispersible tablets 
ABILIFY 15 mg orodispersible tablets 
ABILIFY 30 mg orodispersible tablets 

 
aripiprazole 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What ABILIFY is and what it is used for 
2. What you need to know before you take ABILIFY 
3. How to take ABILIFY 
4. Possible side effects 
5 How to store ABILIFY 
6. Contents of the pack and other information 
 
 
1. What ABILIFY is and what it is used for 
 
ABILIFY contains the active substance aripiprazole and belong to a group of medicines called 
antipsychotics. It is used to treat adults and adolescents aged 15 years and older who suffer from a 
disease characterised by symptoms such as hearing, seeing or sensing things which are not there, 
suspiciousness, mistaken beliefs, incoherent speech and behaviour and emotional flatness. People with 
this condition may also feel depressed, guilty, anxious or tense. 
 
ABILIFY is used to treat adults and adolescents aged 13 years and older who suffer from a condition 
with symptoms such as feeling "high", having excessive amounts of energy, needing much less sleep 
than usual, talking very quickly with racing ideas and sometimes severe irritability. In adults it also 
prevents this condition from returning in patients who have responded to the treatment with ABILIFY. 
 
 
2. What you need to know before you take ABILIFY 
 
Do not take ABILIFY 
• if you are allergic to aripiprazole or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
Talk to your doctor before taking ABILIFY. 
 
Suicidal thoughts and behaviours have been reported during aripiprazole treatment. Tell your doctor 
immediately if you are having any thoughts or feelings about hurting yourself. 
 
Before treatment with ABILIFY, tell your doctor if you suffer from 
• high blood sugar (characterised by symptoms such as excessive thirst, passing of large amounts 

of urine, increase in appetite and feeling weak) or family history of diabetes 
• fits (seizures) since your doctor may want to monitor you more closely 
• involuntary, irregular muscle movements, especially in the face 



 117 

• cardiovascular diseases (diseases of the heart and circulation), family history of cardiovascular 
disease, stroke or "mini" stroke, abnormal blood pressure 

• blood clots, or family history of blood clots, as antipsychotics have been associated with 
formation of blood clots 

• past experience with excessive gambling 
 
If you notice you are gaining weight, develop unusual movements, experience somnolence that 
interferes with normal daily activities, any difficulty in swallowing or allergic symptoms, please tell 
your doctor. 
 
If you are an elderly patient suffering from dementia (loss of memory and other mental abilities), you 
or your carer/relative should tell your doctor if you have ever had a stroke or "mini" stroke. 
 
Tell your doctor immediately if you are having any thoughts or feelings about hurting yourself. 
Suicidal thoughts and behaviours have been reported during aripiprazole treatment. 
 
Tell your doctor immediately if you suffer from muscle stiffness or inflexibility with high fever, 
sweating, altered mental status, or very rapid or irregular heartbeat. 
 
Tell your doctor if you or your family/carer notices that you are developing urges or cravings to 
behave in ways that are unusual for you and you cannot resist the impulse, drive or temptation to carry 
out certain activities that could harm yourself or others. These are called impulse control disorders and 
can include behaviours such as addictive gambling, excessive eating or spending, an abnormally high 
sex drive or preoccupation with an increase in sexual thoughts or feelings. 
Your doctor may need to adjust or stop your dose. 
 
Aripiprazole may cause sleepiness, fall in blood pressure when standing up, dizziness and changes in 
your ability to move and balance, which may lead to falls. Caution should be taken, particularly if you 
are an elderly patient or have some debility. 
 
Children and adolescents 
Do not use this medicine in children and adolescents under 13 years of age. It is not known if it is safe 
and effective in these patients. 
 
Other medicines and ABILIFY 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without a prescription. 
 
Blood pressure-lowering medicines: ABILIFY may increase the effect of medicines used to lower the 
blood pressure. Be sure to tell your doctor if you take a medicine to keep your blood pressure under 
control. 
 
Taking ABILIFY with some medicines may mean the doctor will need to change your dose of 
ABILIFY or the other medicines. It is especially important to mention the following to your doctor: 
 
• medicines to correct heart rhythm (such as quinidine, amiodarone, flecainide) 
• antidepressants or herbal remedy used to treat depression and anxiety (such as fluoxetine, 

paroxetine, venlafaxine, St. John's Wort) 
• antifungal medicines (such as ketoconazole, itraconazole) 
• certain medicines to treat HIV infection (such as efavirenz, nevirapine, an protease inhibitors 

e.g. indinavir, ritonavir) 
• anticonvulsants used to treat epilepsy (such as carbamazepine, phenytoin, phenobarbital) 
• certain antibiotics used to treat tuberculosis (rifabutin, rifampicin) 
 
These medicines may increase the risk of side effects or reduce the effect of ABILIFY; if you get any 
unusual symptom taking any of these medicines together with ABILIFY you should see your doctor. 
 



 118 

Medicines that increase the level of serotonin are typically used in conditions including depression, 
generalised anxiety disorder, obsessive-compulsive disorder (OCD) and social phobia as well as 
migraine and pain: 
 
• triptans, tramadol and tryptophan used for conditions including depression, generalised anxiety 

disorder, obsessive compulsive disorder (OCD) and social phobia as well as migraine and pain 
• selective-serotonin-reuptake-inhibitors (SSRIs) (such as paroxetine and fluoxetine) used for 

depression, OCD, panic and anxiety 
• other anti-depressants (such as venlafaxine and tryptophan) used in major depression 
• tricyclic’s (such as clomipramine and amitriptyline) used for depressive illness 
• St John’s Wort (Hypericum perforatum) used as a herbal remedy for mild depression 
• pain killers (such as tramadol and pethidine) used for pain relief 
• triptans (such as sumatriptan and zolmitripitan) used for treating migraine 
 
These medicines may increase the risk of side effects; if you get any unusual symptom taking any of 
these medicines together with ABILIFY, you should see your doctor. 
 
ABILIFY with food, drink and alcohol 
This medicine can be taken regardless of meals. 
Alcohol should be avoided. 
 
Pregnancy, breast-feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 
The following symptoms may occur in newborn babies, of mothers that have used ABILIFY in the last 
trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, sleepiness, 
agitation, breathing problems, and difficulty in feeding. If your baby develops any of these symptoms 
you may need to contact your doctor. 
 
If you are taking ABILIFY, your doctor will discuss with you whether you should breast-feed 
considering the benefit to you of your therapy and the benefit to your baby of breast-feeding. You 
should not do both. Talk to your doctor about the best way to feed your baby if you are taking this 
medicine. 
 
Driving and using machines 
Dizziness and vision problems may occur during treatment with this medicine (see section 4). 
This should be considered in cases where full alertness is required, e.g., when driving a car or handling 
machines. 
 
ABILIFY contains aspartame 
ABILIFY 10 mg orodispersible tablets: This medicine contains 2 mg aspartame in each tablet. 
ABILIFY 15 mg orodispersible tablets: This medicine contains 3 mg aspartame in each tablet. 
ABILIFY 30 mg orodispersible tablets: This medicine contains 6 mg aspartame in each tablet. 
Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria (PKU), a 
rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly. 
 
ABILIFY contains lactose 
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
ABILIFY contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-
free’. 
 
 
3. How to take ABILIFY 

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 119 

 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
The recommended dose for adults is 15 mg once a day. However your doctor may prescribe a lower 
or higher dose to a maximum of 30 mg once a day. 
 
Use in children and adolescents 
This medicinal product may be started at a low dose with the oral solution (liquid) form. 
The dose may be gradually increased to the recommended dose for adolescents of 10 mg once a 
day. However your doctor may prescribe a lower or higher dose to a maximum of 30 mg once a day. 
 
If you have the impression that the effect of ABILIFY is too strong or too weak, talk to your doctor or 
pharmacist. 
 
Try to take ABILIFY at the same time each day. It does not matter whether you take it with or 
without food. 
 
Do not open the blister until ready to administer. For single tablet removal, open the package and peel 
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 orodispersible tablet on the tongue. Tablet disintegration occurs rapidly in saliva. The 
orodispersible tablet can be taken with or without liquid. 
Alternatively, disperse the tablet in water and drink the resulting suspension. 
 
Even if you feel better, do not alter or discontinue the daily dose of ABILIFY without first consulting 
your doctor. 
 
If you take more ABILIFY than you should 
If you realise you have taken more ABILIFY than your doctor has recommended (or if someone else 
has taken some of your ABILIFY), contact your doctor right away. If you cannot reach your doctor, go 
to the nearest hospital and take the pack with you. 
 
Patients who have taken too much aripiprazole have experienced the following symptoms: 
• rapid heartbeat, agitation/aggressiveness, problems with speech. 
• unusual movements (especially of the face or tongue) and reduced level of consciousness. 
 
Other symptoms may include: 
• acute confusion, seizures (epilepsy), coma, a combination of fever, faster breathing, sweating, 
• muscle stiffness, and drowsiness or sleepiness, slower breathing, choking, high or low blood 

pressure, abnormal rhythms of the heart. 
 
Contact your doctor or hospital immediately if you experience any of the above. 
 
If you forget to take ABILIFY 
If you miss a dose, take the missed dose as soon as you remember but do not take two doses in one 
day. 
 
If you stop taking ABILIFY 
Do not stop your treatment just because you feel better. It is important that you carry on taking 
ABILIFY for as long as your doctor has told you to. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 



 120 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Common side effects (may affect up to 1 in 10 people): 
 
• diabetes mellitus, 
• difficulty sleeping, 
• feeling anxious, 
• feeling restless and unable to keep still, difficulty sitting still, 
• akathisia (an uncomfortable feeling of inner restlessness and a compelling need to move 

constantly), 
• uncontrollable twitching, jerking or writhing movements, 
• trembling, 
• headache, 
• tiredness, 
• sleepiness, 
• light-headedness, 
• shaking and blurred vision, 
• decreased number of or difficulty making bowel movements, 
• indigestion, 
• feeling sick, 
• more saliva in mouth than normal, 
• vomiting, 
• feeling tired. 
 
Uncommon side effects (may affect up to 1 in 100 people): 
 
• increased blood levels of the hormone prolactin, 
• too much sugar in the blood, 
• depression, 
• altered or increased sexual interest, 
• uncontrollable movements of mouth, tongue and limbs (tardive dyskinesia), 
• muscle disorder causing twisting movements (dystonia), 
• restless legs, 
• double vision, 
• eye sensitivity to light, 
• fast heartbeat, 
• a fall in blood pressure on standing up which causes dizziness, light-headedness or fainting, 
• hiccups. 
 
The following side effects have been reported since the marketing of oral aripiprazole but the 
frequency for them to occur is not known: 
 
• low levels of white blood cells, 
• low levels of blood platelets, 
• allergic reaction (e.g. swelling in the mouth, tongue, face and throat, itching, hives), 
• onset or worsening of diabetes, ketoacidosis (ketones in the blood and urine) or coma, 
• high blood sugar, 
• not enough sodium in the blood, 
• loss of appetite (anorexia), 
• weight loss, 
• weight gain, 
• thoughts of suicide, suicide attempt and suicide, 
• feeling aggressive, 
• agitation, 
• nervousness, 
• combination of fever, muscle stiffness, faster breathing, sweating, reduced consciousness and 

sudden changes in blood pressure and heart rate, fainting (neuroleptic malignant syndrome), 



 121 

• seizure, 
• serotonin syndrome (a reaction which may cause feelings of great happiness, drowsiness, 

clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), 
• speech disorder, 
• fixation of the eyeballs in one position, 
• sudden unexplained death, 
• life-threatening irregular heartbeat, 
• heart attack, 
• slower heartbeat, 
• blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in 

the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in 
breathing (if you notice any of these symptoms, seek medical advice immediately), 

• high blood pressure, 
• fainting, 
• accidental inhalation of food with risk of pneumonia (lung infection), 
• spasm of the muscles around the voice box, 
• inflammation of the pancreas, 
• difficulty swallowing, 
• diarrhoea, 
• abdominal discomfort, 
• stomach discomfort, 
• liver failure, 
• inflammation of the liver, 
• yellowing of the skin and white part of eyes, 
• reports of abnormal liver tests values, 
• skin rash, 
• skin sensitivity to light, 
• baldness, 
• excessive sweating, 
• serious allergic reactions such as Drug Reaction with Eosinophilia and Systemic Symptoms 

(DRESS). DRESS appears initially as flu-like symptoms with a rash on the face and then with 
an extended rash, high temperature, enlarged lymph nodes, increased levels of liver enzymes 
seen in blood tests and an increase in a type of white blood cell (eosinophilia), 

• abnormal muscle breakdown which can lead to kidney problems, 
• muscle pain, 
• stiffness, 
• involuntary loss of urine (incontinence), 
• difficulty in passing urine, 
• withdrawal symptoms in newborn babies in case of exposure during pregnancy, 
• prolonged and/or painful erection, 
• difficulty controlling core body temperature or overheating, 
• chest pain, 
• swelling of hands, ankles or feet, 
• in blood tests: increased or fluctuating blood sugar, increased glycosylated haemoglobin. 
• Inability to resist the impulse, drive or temptation to perform an action that could be harmful to 

you or others, which may include: 
- strong impulse to gamble excessively despite serious personal or family consequences 
- altered or increased sexual interest and behaviour of significant concern to you or to 

others, for example, an increased sexual drive 
- uncontrollable excessive shopping 
- binge eating (eating large amounts of food in a short time period) or compulsive eating 

(eating more food than normal and more than is needed to satisfy your hunger) 
- a tendency to wander away. 
Tell your doctor if you experience any of these behaviours; he/she will discuss ways of 
managing or reducing the symptoms. 

 
In elderly patients with dementia, more fatal cases have been reported while taking aripiprazole. In 



 122 

addition, cases of stroke or "mini" stroke have been reported. 
 
Additional side effects in children and adolescents 
Adolescents aged 13 years and older experienced side effects that were similar in frequency and type 
to those in adults except that sleepiness, uncontrollable twitching or jerking movements, restlessness, 
and tiredness were very common (greater than 1 in 10 patients) and upper abdominal pain, dry mouth, 
increased heart rate, weight gain, increased appetite, muscle twitching, uncontrolled movements of the 
limbs, and feeling dizzy, especially when getting up from a lying or sitting position, were common 
(greater than 1 in 100 patients). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store ABILIFY 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the blister and on the carton after 
EXP. The expiry date refers to the last day of that month. 
 
Store in the original package in order to protect from moisture. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What ABILIFY contains 
• The active substance is aripiprazole. 
 Each orodispersible tablet contains 10 mg of aripiprazole. 
 Each orodispersible tablet contains 15 mg of aripiprazole. 
 Each orodispersible tablet contains 30 mg of aripiprazole. 
 
• The other ingredients are calcium silicate, croscarmellose sodium, crospovidone, silicon 

dioxide, xylitol, microcrystalline cellulose, aspartame, acesulfame potassium, vanilla flavour 
(contains lactose), tartaric acid and magnesium stearate. 
Tablet coat 
ABILIFY 10 mg orodispersible tablets: Red iron oxide (E 172) 
ABILIFY 15 mg orodispersible tablets: Yellow iron oxide (E 172) 
ABILIFY 30 mg orodispersible tablets: Red iron oxide (E 172) 
 

What ABILIFY looks like and contents of the pack 
ABILIFY 10 mg orodispersible tablets are round and pink, marked with ‘"A" over "640"’ on one side 
and ‘10’ on the other. 
ABILIFY 15 mg orodispersible tablets are round and yellow, marked with ‘"A" over "641"’ on one 
side and ‘15’ on the other. 
ABILIFY 30 mg orodispersible tablets are round and pink, marked with ‘"A" over "643"’ on one side 
and ‘30’ on the other. 
 
ABILIFY orodispersible tablets are supplied in perforated unit dose blisters packed in cartons 
containing 14 × 1, 28 × 1, or 49 × 1 orodispersible tablets. 
 

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 123 

Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
Manufacturer 
Elaiapharm 
2881 Route des Crêtes, Z.I. Les Bouilides-Sophia Antipolis, 
06560 Valbonne 
France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Lietuva 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

България 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Luxembourg/Luxemburg 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Česká republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Magyarország 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Danmark 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Malta 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Deutschland 
Otsuka Pharma GmbH 
Tel: +49 (0) 69 1700 860 
 

Nederland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Eesti 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Norge 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Ελλάδα 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Österreich 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

España 
Otsuka Pharmaceutical, S.A. 
Tel: +34 93 550 01 00 
 

Polska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

France 
Otsuka Pharmaceutical France SAS 
Tél: +33 (0)1 47 08 00 00 
 

Portugal 
Lundbeck Portugal Lda 
Tel: +351 (0) 21 00 45 900 
 

Hrvatska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

România 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 



 124 

Ireland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Slovenija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Ísland 
Vistor hf. 
Sími: +354 (0) 535 7000 
 

Slovenská republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Italia 
Otsuka Pharmaceutical Italy S.r.l. 
Tel: +39 (0) 2 0063 2710 
 

Suomi/Finland 
Otsuka Pharma Scandinavia AB 
Puh/Tel: +46 (0) 8 545 286 60 
 

Κύπρος 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Sverige 
Otsuka Pharma Scandinavia AB 
Tel: +46 (0) 8 545 286 60 
 

Latvija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

United Kingdom 
Otsuka Pharmaceuticals (UK) Ltd. 
Tel: +44 (0) 203 747 5300 
 

 
This leaflet was last revised in {MM/YYYY} 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

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 125 

Package leaflet: Information for the user 
 

ABILIFY 1 mg/mL oral solution 
aripiprazole 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What ABILIFY is and what it is used for 
2. What you need to know before you take ABILIFY 
3. How to take ABILIFY 
4. Possible side effects 
5 How to store ABILIFY 
6. Contents of the pack and other information 
 
 
1. What ABILIFY is and what it is used for 
 
ABILIFY contains the active substance aripiprazole and belongs to a group of medicines called 
antipsychotics. It is used to treat adults and adolescents aged 15 years and older who suffer from a 
disease characterised by symptoms such as hearing, seeing or sensing things which are not there, 
suspiciousness, mistaken beliefs, incoherent speech and behaviour and emotional flatness. People with 
this condition may also feel depressed, guilty, anxious or tense. 
 
ABILIFY is used to treat adults and adolescents aged 13 years and older who suffer from a condition 
with symptoms such as feeling "high", having excessive amounts of energy, needing much less sleep 
than usual, talking very quickly with racing ideas and sometimes severe irritability. In adults it also 
prevents this condition from returning in patients who have responded to the treatment with ABILIFY. 
 
 
2. What you need to know before you take ABILIFY 
 
Do not take ABILIFY 
• if you are allergic to aripiprazole or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
Talk to your doctor before taking ABILIFY. 
 
Suicidal thoughts and behaviours have been reported during aripiprazole treatment. Tell your doctor 
immediately if you are having any thoughts or feelings about hurting yourself. 
 
Before treatment with ABILIFY, tell your doctor if you suffer from 
• high blood sugar (characterised by symptoms such as excessive thirst, passing of large amounts 

of urine, increase in appetite and feeling weak) or family history of diabetes 
• fits (seizures) since your doctor may want to monitor you more closely 
• involuntary, irregular muscle movements, especially in the face 
• cardiovascular diseases (diseases of the heart and circulation), family history of cardiovascular 

disease, stroke or "mini" stroke, abnormal blood pressure 



 126 

• blood clots, or family history of blood clots, as antipsychotics have been associated with 
formation of blood clots 

• past experience with excessive gambling 
 
If you notice you are gaining weight, develop unusual movements, experience somnolence that 
interferes with normal daily activities, any difficulty in swallowing or allergic symptoms, please tell 
your doctor. 
 
If you are an elderly patient suffering from dementia (loss of memory and other mental abilities), you 
or your carer/relative should tell your doctor if you have ever had a stroke or "mini" stroke. 
 
Tell your doctor immediately if you are having any thoughts or feelings about hurting yourself. 
Suicidal thoughts and behaviours have been reported during aripiprazole treatment. 
 
Tell your doctor immediately if you suffer from muscle stiffness or inflexibility with high fever, 
sweating, altered mental status, or very rapid or irregular heartbeat. 
 
Tell your doctor if you or your family/carer notices that you are developing urges or cravings to 
behave in ways that are unusual for you and you cannot resist the impulse, drive or temptation to carry 
out certain activities that could harm yourself or others. These are called impulse control disorders and 
can include behaviours such as addictive gambling, excessive eating or spending, an abnormally high 
sex drive or preoccupation with an increase in sexual thoughts or feelings. 
Your doctor may need to adjust or stop your dose. 
 
Aripiprazole may cause sleepiness, fall in blood pressure when standing up, dizziness and changes in 
your ability to move and balance, which may lead to falls. Caution should be taken, particularly if you 
are an elderly patient or have some debility. 
 
Children and adolescents 
Do not use this medicine in children and adolescents under 13 years of age. It is not known if it is safe 
and effective in these patients. 
 
Other medicines and ABILIFY 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without a prescription. 
 
Blood pressure-lowering medicines: ABILIFY may increase the effect of medicines used to lower the 
blood pressure. Be sure to tell your doctor if you take a medicine to keep your blood pressure under 
control. 
 
Taking ABILIFY with some medicines may mean the doctor will need to change your dose of 
ABILIFY or the other medicines. It is especially important to mention the following to your doctor: 
 
• medicines to correct heart rhythm (such as quinidine, amiodarone, flecainide) 
• antidepressants or herbal remedy used to treat depression and anxiety (such as fluoxetine, 

paroxetine, venlafaxine, St. John's Wort) 
• antifungal medicines (such as ketoconazole, itraconazole) 
• certain medicines to treat HIV infection (such as efavirenz, nevirapine, an protease inhibitors 

e.g. indinavir, ritonavir) 
• anticonvulsants used to treat epilepsy (such as carbamazepine, phenytoin, phenobarbital) 
• certain antibiotics used to treat tuberculosis (rifabutin, rifampicin) 
 
These medicines may increase the risk of side effects or reduce the effect of ABILIFY; if you get any 
unusual symptom taking any of these medicines together with ABILIFY you should see your doctor. 
 



 127 

Medicines that increase the level of serotonin are typically used in conditions including depression, 
generalised anxiety disorder, obsessive-compulsive disorder (OCD) and social phobia as well as 
migraine and pain: 
 
• triptans, tramadol and tryptophan used for conditions including depression, generalised anxiety 

disorder, obsessive compulsive disorder (OCD) and social phobia as well as migraine and pain 
• selective-serotonin-reuptake-inhibitors (SSRIs) (such as paroxetine and fluoxetine) used for 

depression, OCD, panic and anxiety 
• other anti-depressants (such as venlafaxine and tryptophan) used in major depression 
• tricyclic’s (such as clomipramine and amitriptyline) used for depressive illness 
• St John’s Wort (Hypericum perforatum) used as a herbal remedy for mild depression 
• pain killers (such as tramadol and pethidine) used for pain relief 
• triptans (such as sumatriptan and zolmitripitan) used for treating migraine 
 
These medicines may increase the risk of side effects; if you get any unusual symptom taking any of 
these medicines together with ABILIFY, you should see your doctor. 
 
ABILIFY with food, drink and alcohol 
This medicine can be taken regardless of meals. However, the oral solution should not be diluted with 
other liquids or mixed with any food prior to administration. 
Alcohol should be avoided. 
 
Pregnancy, breast-feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 
The following symptoms may occur in newborn babies, of mothers that have used ABILIFY in the last 
trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, sleepiness, 
agitation, breathing problems, and difficulty in feeding. If your baby develops any of these symptoms 
you may need to contact your doctor. 
 
If you are taking ABILIFY, your doctor will discuss with you whether you should breast-feed 
considering the benefit to you of your therapy and the benefit to your baby of breast-feeding. You 
should not do both. Talk to your doctor about the best way to feed your baby if you are taking this 
medicine. 
 
Driving and using machines 
Dizziness and vision problems may occur during treatment with this medicine (see section 4). 
This should be considered in cases where full alertness is required, e.g., when driving a car or handling 
machines. 
 
ABILIFY contains fructose and sucrose 
This medicine contains 200 mg of fructose and 400 mg of sucrose in each mL. If you have been told 
by your doctor that you have an intolerance to some sugars, contact your doctor before taking this 
medicine. Fructose may damage teeth. Sucrose may be harmful to the teeth. 
 
ABILIFY contains parahydroxybenzoates 
May cause allergic reactions (possibly delayed). 
 
ABILIFY contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially 
‘sodium-free’. 
 
 
3. How to take ABILIFY 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 

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 128 

or pharmacist if you are not sure. 
 
The recommended dose for adults is 15 mL solution (corresponding to 15 mg aripiprazole) once 
a day. However your doctor may prescribe a lower or higher dose to a maximum of 30 mg (i.e. 
30 mL) once a day. 
 
Use in children and adolescents 
The recommended dose for adolescents is 10 mL solution (corresponding to 10 mg aripiprazole) 
once a day. However your doctor may prescribe a lower or higher dose to a maximum of 30 mL (i.e. 
30 mg) once a day. 
 
The dose of ABILIFY must be measured using the calibrated cup or the 2 mL calibrated dropping 
pipette supplied in the carton. 
 
If you have the impression that the effect of ABILIFY is too strong or too weak, talk to your doctor or 
pharmacist. 
 
Try to take ABILIFY at the same time each day. It does not matter whether you take it with or 
without food. However, you should not dilute with other liquids or mix with other food prior to taking 
ABILIFY oral solution. 
 
Even if you feel better, do not alter or discontinue the daily dose of ABILIFY without first consulting 
your doctor. 
 
If you take more ABILIFY than you should 
If you realise you have taken more ABILIFY than your doctor has recommended (or if someone else 
has taken some of your ABILIFY), contact your doctor right away. If you cannot reach your doctor, go 
to the nearest hospital and take the pack with you. 
 
Patients who have taken too much aripiprazole have experienced the following symptoms: 
• rapid heartbeat, agitation/aggressiveness, problems with speech. 
• unusual movements (especially of the face or tongue) and reduced level of consciousness. 
 
Other symptoms may include: 
• acute confusion, seizures (epilepsy), coma, a combination of fever, faster breathing, sweating, 
• muscle stiffness, and drowsiness or sleepiness, slower breathing, choking, high or low blood 

pressure, abnormal rhythms of the heart. 
 
Contact your doctor or hospital immediately if you experience any of the above. 
 
If you forget to take ABILIFY 
If you miss a dose, take the missed dose as soon as you remember but do not take two doses in one 
day. 
 
If you stop taking ABILIFY 
Do not stop your treatment just because you feel better. It is important that you carry on taking 
ABILIFY for as long as your doctor has told you to. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Common side effects (may affect up to 1 in 10 people): 
 



 129 

• diabetes mellitus, 
• difficulty sleeping, 
• feeling anxious, 
• feeling restless and unable to keep still, difficulty sitting still, 
• akathisia (an uncomfortable feeling of inner restlessness and a compelling need to move 

constantly), 
• uncontrollable twitching, jerking or writhing movements, 
• trembling, 
• headache, 
• tiredness, 
• sleepiness, 
• light-headedness, 
• shaking and blurred vision, 
• decreased number of or difficulty making bowel movements, 
• indigestion, 
• feeling sick, 
• more saliva in mouth than normal, 
• vomiting, 
• feeling tired. 
 
Uncommon side effects (may affect up to 1 in 100 people): 
 
• increased blood levels of the hormone prolactin, 
• too much sugar in the blood, 
• depression, 
• altered or increased sexual interest, 
• uncontrollable movements of mouth, tongue and limbs (tardive dyskinesia), 
• muscle disorder causing twisting movements (dystonia), 
• restless legs, 
• double vision, 
• eye sensitivity to light, 
• fast heartbeat, 
• a fall in blood pressure on standing up which causes dizziness, light-headedness or fainting, 
• hiccups. 
 
The following side effects have been reported since the marketing of oral aripiprazole but the 
frequency for them to occur is not known: 
 
• low levels of white blood cells, 
• low levels of blood platelets, 
• allergic reaction (e.g. swelling in the mouth, tongue, face and throat, itching, hives), 
• onset or worsening of diabetes, ketoacidosis (ketones in the blood and urine) or coma, 
• high blood sugar, 
• not enough sodium in the blood, 
• loss of appetite (anorexia), 
• weight loss, 
• weight gain, 
• thoughts of suicide, suicide attempt and suicide, 
• feeling aggressive, 
• agitation, 
• nervousness, 
• combination of fever, muscle stiffness, faster breathing, sweating, reduced consciousness and 

sudden changes in blood pressure and heart rate, fainting (neuroleptic malignant syndrome), 
• seizure, 
• serotonin syndrome (a reaction which may cause feelings of great happiness, drowsiness, 

clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), 
• speech disorder, 



 130 

• fixation of the eyeballs in one position, 
• sudden unexplained death, 
• life-threatening irregular heartbeat, 
• heart attack, 
• slower heartbeat, 
• blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in 

the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in 
breathing (if you notice any of these symptoms, seek medical advice immediately), 

• high blood pressure, 
• fainting, 
• accidental inhalation of food with risk of pneumonia (lung infection), 
• spasm of the muscles around the voice box, 
• inflammation of the pancreas, 
• difficulty swallowing, 
• diarrhoea, 
• abdominal discomfort, 
• stomach discomfort, 
• liver failure, 
• inflammation of the liver, 
• yellowing of the skin and white part of eyes, 
• reports of abnormal liver tests values, 
• skin rash, 
• skin sensitivity to light, 
• baldness, 
• excessive sweating, 
• serious allergic reactions such as Drug Reaction with Eosinophilia and Systemic Symptoms 

(DRESS). DRESS appears initially as flu-like symptoms with a rash on the face and then with 
an extended rash, high temperature, enlarged lymph nodes, increased levels of liver enzymes 
seen in blood tests and an increase in a type of white blood cell (eosinophilia), 

• abnormal muscle breakdown which can lead to kidney problems, 
• muscle pain, 
• stiffness, 
• involuntary loss of urine (incontinence), 
• difficulty in passing urine, 
• withdrawal symptoms in newborn babies in case of exposure during pregnancy, 
• prolonged and/or painful erection, 
• difficulty controlling core body temperature or overheating, 
• chest pain, 
• swelling of hands, ankles or feet, 
• in blood tests: increased or fluctuating blood sugar, increased glycosylated haemoglobin. 
• Inability to resist the impulse, drive or temptation to perform an action that could be harmful to 

you or others, which may include: 
- strong impulse to gamble excessively despite serious personal or family consequences 
- altered or increased sexual interest and behaviour of significant concern to you or to 

others, for example, an increased sexual drive 
- uncontrollable excessive shopping 
- binge eating (eating large amounts of food in a short time period) or compulsive eating 

(eating more food than normal and more than is needed to satisfy your hunger) 
- a tendency to wander away. 
Tell your doctor if you experience any of these behaviours; he/she will discuss ways of 
managing or reducing the symptoms. 

 
In elderly patients with dementia, more fatal cases have been reported while taking aripiprazole. In 
addition, cases of stroke or "mini" stroke have been reported. 
 
Additional side effects in children and adolescents 
Adolescents aged 13 years and older experienced side effects that were similar in frequency and type 



 131 

to those in adults except that sleepiness, uncontrollable twitching or jerking movements, restlessness, 
and tiredness were very common (greater than 1 in 10 patients) and upper abdominal pain, dry mouth, 
increased heart rate, weight gain, increased appetite, muscle twitching, uncontrolled movements of the 
limbs, and feeling dizzy, especially when getting up from a lying or sitting position, were common 
(greater than 1 in 100 patients). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store ABILIFY 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the bottle and on the carton after 
EXP. The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
Use within 6 months after first opening. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What ABILIFY contains 
• The active substance is aripiprazole. 

Each mL contains 1 mg of aripiprazole. 
 
• The other ingredients are disodium edetate, fructose, glycerin, lactic acid, methyl 

parahydroxybenzoate (E218), propylene glycol, propyl parahydroxybenzoate (E216), sodium 
hydroxide, sucrose, purified water, and orange flavour. 

 
What ABILIFY looks like and contents of the pack 
ABILIFY 1 mg/mL oral solution is a clear, colourless to light yellow liquid supplied in bottles with 
polypropylene child-resistant closure containing 50 mL, 150 mL or 480 mL per bottle. 
 
Each carton contains one bottle and both a calibrated polypropylene measuring cup and a calibrated 
polypropylene low-density polyethylene dropping pipette. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
Manufacturer 
Elaiapharm 
2881 Route des Crêtes, Z.I. Les Bouilides-Sophia Antipolis, 
06560 Valbonne 
France 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 132 

 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Lietuva 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

България 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Luxembourg/Luxemburg 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Česká republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Magyarország 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Danmark 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Malta 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Deutschland 
Otsuka Pharma GmbH 
Tel: +49 (0) 69 1700 860 
 

Nederland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Eesti 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Norge 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Ελλάδα 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Österreich 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

España 
Otsuka Pharmaceutical, S.A. 
Tel: +34 93 550 01 00 
 

Polska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

France 
Otsuka Pharmaceutical France SAS 
Tél: +33 (0)1 47 08 00 00 
 

Portugal 
Lundbeck Portugal Lda 
Tel: +351 (0) 21 00 45 900 
 

Hrvatska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

România 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Ireland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Slovenija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Ísland 
Vistor hf. 
Sími: +354 (0) 535 7000 
 

Slovenská republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Italia 
Otsuka Pharmaceutical Italy S.r.l. 
Tel: +39 (0) 2 0063 2710 
 

Suomi/Finland 
Otsuka Pharma Scandinavia AB 
Puh/Tel: +46 (0) 8 545 286 60 
 



 133 

Κύπρος 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Sverige 
Otsuka Pharma Scandinavia AB 
Tel: +46 (0) 8 545 286 60 
 

Latvija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

United Kingdom 
Otsuka Pharmaceuticals (UK) Ltd. 
Tel: +44 (0) 203 747 5300 
 

 
This leaflet was last revised in {MM/YYYY} 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

http://www.ema.europa.eu/


 134 

Package leaflet: Information for the user 
 

ABILIFY 7.5 mg/mL solution for injection 
aripiprazole 

 
Read all of this leaflet carefully before you receive this medicine because it contains important 
information for you. 
• Keep this leaflet. You may need to read it again. 
• If you have any further questions, ask your doctor or pharmacist. 
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What ABILIFY is and what it is used for 
2. What you need to know before you are given ABILIFY 
3. How ABILIFY is given 
4. Possible side effects 
5. How to store ABILIFY 
6. Contents of the pack and other information 
 
 
1. What ABILIFY is and what it is used for 
 
ABILIFY contains the active substance aripiprazole and belongs to a group of medicines called 
antipsychotics. ABILIFY is used to treat quickly symptoms of agitation and distressing behaviour that 
may occur in a disease characterised by symptoms such as: 
• hearing, seeing or sensing things which are not there, suspiciousness, mistaken beliefs, 

incoherent speech and behaviour and emotional flatness. People with this condition may also 
feel depressed, guilty, anxious or tense. 

• feeling "high", having excessive amounts of energy, needing much less sleep than usual, talking 
very quickly with racing ideas and sometimes severe irritability. 

 
ABILIFY is given when treatment with oral formulations is not appropriate. Your doctor will change 
your treatment to oral ABILIFY as soon as appropriate. 
 
 
2. What you need to know before you are given ABILIFY 
 
Do not use ABILIFY 
• if you are allergic to aripiprazole or any of the other ingredients of this medicine (listed in 

section 6). 
 
Warnings and precautions 
Talk to your doctor before you are given ABILIFY. 
 
Suicidal thoughts and behaviours have been reported during aripiprazole treatment. Tell your doctor 
immediately if you are having any thoughts or feelings about hurting yourself. 
 
Before treatment with ABILIFY, tell your doctor if you suffer from 
• high blood sugar (characterised by symptoms such as excessive thirst, passing of large amounts 

of urine, increase in appetite and feeling weak) or family history of diabetes 
• fits (seizures) since your doctor may want to monitor you more closely 
• involuntary, irregular muscle movements, especially in the face 
• cardiovascular diseases (diseases of the heart and circulation), family history of cardiovascular 

disease, stroke or "mini" stroke, abnormal blood pressure 



 135 

• blood clots, or family history of blood clots, as antipsychotics have been associated with 
formation of blood clots 

• past experience with excessive gambling 
 
If you notice you are gaining weight, develop unusual movements, experience somnolence that 
interferes with normal daily activities, any difficulty in swallowing or allergic symptoms, please tell 
your doctor. 
 
If you are an elderly patient suffering from dementia (loss of memory and other mental abilities), you 
or your carer/relative should tell your doctor if you have ever had a stroke or "mini" stroke. 
 
Tell the doctor or nurse if you feel dizzy or faint after the injection. You will probably need to lie 
down until you feel better. The doctor may also want to measure your blood pressure and pulse. 
 
Tell your doctor immediately if you are having any thoughts or feelings about hurting yourself. 
Suicidal thoughts and behaviours have been reported during aripiprazole treatment. 
 
Tell your doctor immediately if you suffer from muscle stiffness or inflexibility with high fever, 
sweating, altered mental status, or very rapid or irregular heartbeat. 
 
Tell your doctor if you or your family/carer notices that you are developing urges or cravings to 
behave in ways that are unusual for you and you cannot resist the impulse, drive or temptation to carry 
out certain activities that could harm yourself or others. These are called impulse control disorders and 
can include behaviours such as addictive gambling, excessive eating or spending, an abnormally high 
sex drive or preoccupation with an increase in sexual thoughts or feelings. 
Your doctor may need to adjust or stop your dose. 
 
Aripiprazole may cause sleepiness, fall in blood pressure when standing up, dizziness and changes in 
your ability to move and balance, which may lead to falls. Caution should be taken, particularly if you 
are an elderly patient or have some debility. 
 
Children and adolescents 
Do not use this medicine in children and adolescents under 18 years of age. It is not known if it is safe 
and effective in these patients. 
 
Other medicines and ABILIFY 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 
 
Blood pressure-lowering medicines: ABILIFY may increase the effect of medicines used to lower the 
blood pressure. Be sure to tell your doctor if you take a medicine to keep your blood pressure under 
control. 
 
Receiving ABILIFY with some medicines may mean the doctor will need to change your dose of 
ABILIFY or the other medicines. It is especially important to mention the following to your doctor: 
 
• medicines to correct heart rhythm (such as quinidine, amiodarone, flecainide) 
• antidepressants or herbal remedy used to treat depression and anxiety (such as fluoxetine, 

paroxetine, venlafaxine, St. John's Wort) 
• antifungal medicines (such as ketoconazole, itraconazole) 
• certain medicines to treat HIV infection (such as efavirenz, nevirapine, an protease inhibitors 

e.g. indinavir, ritonavir) 
• anticonvulsants used to treat epilepsy (such as carbamazepine, phenytoin, phenobarbital) 
• certain antibiotics used to treat tuberculosis (rifabutin, rifampicin) 
 
These medicines may increase the risk of side effects or reduce the effect of ABILIFY; if you get any 
unusual symptom taking any of these medicines together with ABILIFY you should see your doctor. 



 136 

 
Medicines that increase the level of serotonin are typically used in conditions including depression, 
generalised anxiety disorder, obsessive-compulsive disorder (OCD) and social phobia as well as 
migraine and pain: 
 
• triptans, tramadol and tryptophan used for conditions including depression, generalised anxiety 

disorder, obsessive compulsive disorder (OCD) and social phobia as well as migraine and pain 
• selective-serotonin-reuptake-inhibitors (SSRIs) (such as paroxetine and fluoxetine) used for 

depression, OCD, panic and anxiety 
• other anti-depressants (such as venlafaxine and tryptophan) used in major depression 
• tricyclic’s (such as clomipramine and amitriptyline) used for depressive illness 
• St John’s Wort (Hypericum perforatum) used as a herbal remedy for mild depression 
• pain killers (such as tramadol and pethidine) used for pain relief 
• triptans (such as sumatriptan and zolmitripitan) used for treating migraine 
 
These medicines may increase the risk of side effects; if you get any unusual symptom taking any of 
these medicines together with ABILIFY, you should see your doctor. 
 
A combination of ABILIFY with medicines taken for anxiety might make you feel drowsy or dizzy. 
Only take other medicines while you are on ABILIFY if your doctor tells you that you can. 
 
ABILIFY with food, drink and alcohol 
This medicine can be given regardless of meals. 
Alcohol should be avoided. 
 
Pregnancy, breast-feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 
The following symptoms may occur in newborn babies, of mothers that have used ABILIFY in the last 
trimester (last three months of their pregnancy): shaking, muscle stiffness and/or weakness, sleepiness, 
agitation, breathing problems, and difficulty in feeding. If your baby develops any of these symptoms 
you may need to contact your doctor. 
 
If you are receiving ABILIFY, your doctor will discuss with you whether you should breast-feed 
considering the benefit to you of your therapy and the benefit to your baby of breast-feeding. You 
should not do both. Talk to your doctor about the best way to feed your baby if you are receiving this 
medicine. 
 
Driving and using machines 
Dizziness and vision problems may occur during treatment with this medicine (see section 4). 
This should be considered in cases where full alertness is required, e.g., when driving a car or handling 
machines. 
 
ABILIFY contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially 
‘sodium-free’. 
 
 
3. How ABILIFY is given 
 
Your doctor will decide how much ABILIFY you need and how long you need it for. The 
recommended dose is 9.75 mg (1.3 mL) for the first injection. Up to three injections in 24 hours may 
be given. The total dose of ABILIFY (all formulations) should not exceed 30 mg per day. 
 
ABILIFY is ready to use. The correct amount of solution will be injected into your muscle by your 
doctor or nurse. 

http://en.wikipedia.org/wiki/Major_depressive_disorder
http://en.wikipedia.org/wiki/Generalized_anxiety_disorder
http://en.wikipedia.org/wiki/Social_anxiety_disorder


 137 

 
If you are given more ABILIFY than you need 
This medicine will be given to you under medical supervision; it is therefore unlikely that you will be 
given too much. If you see more than one doctor, be sure to tell them that you are receiving ABILIFY. 
 
Patients who have been given too much aripiprazole have experienced the following symptoms: 
• rapid heartbeat, agitation/aggressiveness, problems with speech. 
• unusual movements (especially of the face or tongue) and reduced level of consciousness. 
 
Other symptoms may include: 
• acute confusion, seizures (epilepsy), coma, a combination of fever, faster breathing, sweating, 
• muscle stiffness, and drowsiness or sleepiness, slower breathing, choking, high or low blood 

pressure, abnormal rhythms of the heart. 
 
Contact your doctor or hospital immediately if you experience any of the above. 
 
If you miss an injection of ABILIFY 
It is important not to miss your dose. If you miss an injection, you should contact your doctor to 
arrange your next injection as soon as you can. 
 
If you stop receiving ABILIFY 
Do not stop your treatment just because you feel better. It is important that you carry on receiving 
ABILIFY solution for injection for as long as your doctor has told you to. 
 
If you have any further questions on the use of this medicine, ask your doctor or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Common side effects (may affect up to 1 in 10 people): 
 
• diabetes mellitus, 
• difficulty sleeping, 
• feeling anxious, 
• feeling restless and unable to keep still, difficulty sitting still, 
• akathisia (an uncomfortable feeling of inner restlessness and a compelling need to move 

constantly), 
• uncontrollable twitching, jerking or writhing movements, 
 
• trembling, 
• headache, 
• tiredness, 
• sleepiness, 
• light-headedness, 
• shaking and blurred vision, 
• decreased number of or difficulty making bowel movements, 
• indigestion, 
• feeling sick, 
• more saliva in mouth than normal, 
• vomiting, 
• feeling tired. 
 
Uncommon side effects (may affect up to 1 in 100 people): 
 
• increased blood levels of the hormone prolactin, 



 138 

• too much sugar in the blood, 
• depression, 
• altered or increased sexual interest, 
• uncontrollable movements of mouth, tongue and limbs (tardive dyskinesia), 
• muscle disorder causing twisting movements (dystonia), 
• restless legs, 
• double vision, 
• eye sensitivity to light, 
• fast heartbeat, 
• increased diastolic blood pressure, 
• a fall in blood pressure on standing up which causes dizziness, light-headedness or fainting, 
• hiccups, 
• dry mouth. 
 
The following side effects have been reported since the marketing of oral aripiprazole but the 
frequency for them to occur is not known: 
 
• low levels of white blood cells, 
• low levels of blood platelets, 
• allergic reaction (e.g. swelling in the mouth, tongue, face and throat, itching, hives), 
• onset or worsening of diabetes, ketoacidosis (ketones in the blood and urine) or coma, 
• high blood sugar, 
• not enough sodium in the blood, 
• loss of appetite (anorexia), 
• weight loss, 
• weight gain, 
• thoughts of suicide, suicide attempt and suicide, 
• feeling aggressive, 
• agitation, 
• nervousness, 
• combination of fever, muscle stiffness, faster breathing, sweating, reduced consciousness and 

sudden changes in blood pressure and heart rate, fainting (neuroleptic malignant syndrome), 
• seizure, 
• serotonin syndrome (a reaction which may cause feelings of great happiness, drowsiness, 

clumsiness, restlessness, feeling of being drunk, fever, sweating or rigid muscles), 
• speech disorder, 
• fixation of the eyeballs in one position, 
• sudden unexplained death, 
• life-threatening irregular heartbeat, 
• heart attack, 
• slower heartbeat, 
• blood clots in the veins especially in the legs (symptoms include swelling, pain and redness in 

the leg), which may travel through blood vessels to the lungs causing chest pain and difficulty in 
breathing (if you notice any of these symptoms, seek medical advice immediately), 

• high blood pressure, 
• fainting, 
• accidental inhalation of food with risk of pneumonia (lung infection), 
• spasm of the muscles around the voice box, 
• inflammation of the pancreas, 
• difficulty swallowing, 
• diarrhoea, 
• abdominal discomfort, 
• stomach discomfort, 
• liver failure, 
• inflammation of the liver, 
• yellowing of the skin and white part of eyes, 
• reports of abnormal liver tests values, 



 139 

• skin rash, 
• skin sensitivity to light, 
• baldness, 
• excessive sweating, 
• serious allergic reactions such as Drug Reaction with Eosinophilia and Systemic Symptoms 

(DRESS). DRESS appears initially as flu-like symptoms with a rash on the face and then with 
an extended rash, high temperature, enlarged lymph nodes, increased levels of liver enzymes 
seen in blood tests and an increase in a type of white blood cell (eosinophilia), 

• abnormal muscle breakdown which can lead to kidney problems, 
• muscle pain, 
• stiffness, 
• involuntary loss of urine (incontinence), 
• difficulty in passing urine, 
• withdrawal symptoms in newborn babies in case of exposure during pregnancy, 
• prolonged and/or painful erection, 
• difficulty controlling core body temperature or overheating, 
• chest pain, 
• swelling of hands, ankles or feet, 
• in blood tests: increased or fluctuating blood sugar, increased glycosylated haemoglobin. 
• Inability to resist the impulse, drive or temptation to perform an action that could be harmful to 

you or others, which may include: 
- strong impulse to gamble excessively despite serious personal or family consequences 
- altered or increased sexual interest and behaviour of significant concern to you or to 

others, for example, an increased sexual drive 
- uncontrollable excessive shopping 
- binge eating (eating large amounts of food in a short time period) or compulsive eating 

(eating more food than normal and more than is needed to satisfy your hunger) 
- a tendency to wander away. 
Tell your doctor if you experience any of these behaviours; he/she will discuss ways of 
managing or reducing the symptoms. 

 
In elderly patients with dementia, more fatal cases have been reported while taking aripiprazole. In 
addition, cases of stroke or "mini" stroke have been reported. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store ABILIFY 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and on the vial after EXP. 
The expiry date refers to the last day of that month. 
 
Keep the vial in the outer carton in order to protect from light. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What ABILIFY contains 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 140 

• The active substance is aripiprazole. 
Each mL contains 7.5 mg aripiprazole. 
A vial contains 9.75 mg (1.3 mL) aripiprazole. 

 
• The other ingredients are sulfobutylether β-cyclodextrin (SBECD), tartaric acid, sodium 

hydroxide, and water for injections. 
 
What ABILIFY looks like and contents of the pack 
The ABILIFY solution for injection is a clear, colourless, aqueous solution. 
 
Each carton contains one single-use type I glass vial with a rubber butyl stopper and a "tear-off" 
aluminium seal. 
 
Marketing Authorisation Holder 
Otsuka Pharmaceutical Netherlands B.V. 
Herikerbergweg 292 
1101 CT, Amsterdam 
Netherlands 
 
Manufacturer 
Zambon S.p.A. 
Via della Chimica, 9 
I-36100 Vicenza(VI) 
Italy 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Lietuva 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

България 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Luxembourg/Luxemburg 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Česká republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Magyarország 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Danmark 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Malta 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Deutschland 
Otsuka Pharma GmbH 
Tel: +49 (0) 69 1700 860 
 

Nederland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Eesti 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Norge 
Otsuka Pharma Scandinavia AB 
Tlf: +46 (0) 8 545 286 60 
 

Ελλάδα 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Österreich 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 



 141 

España 
Otsuka Pharmaceutical, S.A. 
Tel: +34 93 550 01 00 
 

Polska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

France 
Otsuka Pharmaceutical France SAS 
Tél: +33 (0)1 47 08 00 00 
 

Portugal 
Lundbeck Portugal Lda 
Tel: +351 (0) 21 00 45 900 
 

Hrvatska 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

România 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Ireland 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Slovenija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Ísland 
Vistor hf. 
Sími: +354 (0) 535 7000 
 

Slovenská republika 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Italia 
Otsuka Pharmaceutical Italy S.r.l. 
Tel: +39 (0) 2 0063 2710 
 

Suomi/Finland 
Otsuka Pharma Scandinavia AB 
Puh/Tel: +46 (0) 8 545 286 60 
 

Κύπρος 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

Sverige 
Otsuka Pharma Scandinavia AB 
Tel: +46 (0) 8 545 286 60 
 

Latvija 
Otsuka Pharmaceutical Netherlands B.V. 
Tel: +31 (0) 20 85 46 555 
 

United Kingdom 
Otsuka Pharmaceuticals (UK) Ltd. 
Tel: +44 (0) 203 747 5300 
 

 
This leaflet was last revised in {MM/YYYY} 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET