Special Warning : אזהרת שימוש

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.

U   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 28T       28T


 treatment with aripiprazole (see section 4.8). Close supervision of high-risk patients should accompany antipsychotic therapy.

Results of an epidemiological study suggested that there was no increased risk of suicidality with aripiprazole compared to other antipsychotics among adult patients with schizophrenia or bipolar disorder.


U   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.

U   QT prolongation

In clinical trials of aripiprazole, the incidence of QT prolongation was comparable to placebo. As with other antipsychotics, aripiprazole should be used with caution in patients with a family history of QT prolongation (see section 4.8).

U   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.

U   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.

U   Neuroleptic Malignant Syndrome (NMS)

NMS is a potentially fatal symptom complex associated with antipsychotic medicinal products. 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 antipsychotic active substances, including aripiprazole, must be discontinued.

U   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).

U   Elderly patients with dementia-related psychosis

Increased mortality
In three placebo-controlled trials (n = 938; mean age: 82.4 years; range: 56-99 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: 78-88 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 dementia-related psychosis.

U   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 antipsychotic medicinal products, 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 antipsychotic medicinal products are not available to allow direct comparisons. Patients treated with any antipsychotic medicinal products, 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).

U   Hypersensitivity

As with other medicinal products, hypersensitivity reactions, characterised by allergic symptoms, may occur with aripiprazole (see section 4.8).

U   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).

U   Dysphagia

Oesophageal dysmotility and aspiration have been associated with antipsychotic medicinal product use, including aripiprazole. Aripiprazole and other antipsychotic active substances should be used cautiously in patients at risk for aspiration pneumonia.

U   Pathological gambling

Post-marketing reports of pathological gambling have been reported among patients prescribed aripiprazole, regardless of whether these patients had a prior history of gambling. Patients with a prior history of pathological gambling may be at increased risk and should be monitored carefully (see section 4.8).

U   Serious impulse-control problems:

Serious impulse-control problems, particularly pathological gambling (see the above section), have been reported in patients treated with aripiprazole. These uncontrollable urges were reported to have stopped when the dose was reduced or the medicine was discontinued.
Other uncontrollable urges reported less frequently (post marketing) than gambling include compulsive sexual behaviors, compulsive spending or shopping, binge or compulsive eating, and other urges with impulsive and compulsive features.
Patients and caregivers should be informed of the possibility of these uncontrollable urges when prescribing aripiprazole, and patients should be asked about any new or increasing urges while they are being treated with aripiprazole.
Patients should be advised to talk with their health care professional right away, if they experience new or increasing impulsive or compulsive behaviors, while on treatment.
Lowering the dose or stopping aripiprazole should be considered, if a patient develops new or increased impulsive or compulsive behaviors.

U   Lactose

ABILIFY tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

U   Patients with 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.

Effects on Driving

4.7       Effects on ability to drive and use machines

As with other antipsychotics, patients should be cautioned about operating hazardous machines, including motor vehicles, until they are reasonably certain that aripiprazole does not affect them adversely (see section 4.8).