Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Suicidal ideation and behaviour
The possibility of suicidality (suicidal ideation, suicide attempt and completed suicide) is inherent in psychotic illnesses and, generally, it is reported early after initiation or switch of antipsychotic therapy.
Close supervision of high-risk patients should accompany antipsychotic therapy.

Akathisia, restlessness
Akathisia and restlessness are frequently occurring adverse reactions of antipsychotics. Akathisia is a movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion, as well as by actions such as rocking while standing or sitting, lifting the feet as if marching on the spot, and crossing and uncrossing the legs while sitting. As cariprazine causes akathisia and restlessness, it should be used cautiously in patients who are prone to or already exhibit symptoms of akathisia. Akathisia develops early in treatment. Therefore, close monitoring in the first phase of treatment is important. Prevention includes slow up-titration; treatment measures include slight down- titration of cariprazine or anti-extrapyramidal symptoms (EPS) medicinal product. The dose can be modified based on individual response and tolerability (see section 4.8).

Tardive dyskinesia
Tardive dyskinesia is a syndrome consisting of potentially irreversible, rhythmical, involuntary movements, predominantly of the tongue and/or face that can develop in patients treated with antipsychotics. If signs and symptoms of tardive dyskinesia appear in a patient treated with cariprazine, discontinuation should be considered.

Parkinson's disease
If prescribed to patients with Parkinson's disease, antipsychotic medicinal products may exacerbate the underlying disease and worsen symptoms of Parkinson’s disease. Physicians should, therefore, weigh the risks versus the benefits when prescribing cariprazine to patients with Parkinson's disease.

Ocular symptoms/cataract
In the preclinical studies of cariprazine lens opacity/cataract was detected in dogs (see sections 4.8 and 5.3). However, a causal relationship between lenticular changes / cataracts observed in human studies and cariprazine use has not been established. Nevertheless, patients who would develop symptoms potentially related to cataract should be advised to ophthalmologic examination and re-evaluated for treatment continuation.

Neuroleptic malignant syndrome (NMS)
A potentially fatal symptom complex referred to as NMS has been reported in association with antipsychotic treatment. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, elevated serum creatine phosphokinase levels, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, cariprazine must be discontinued immediately.

Seizures and convulsions
Cariprazine should be used cautiously in patients with history of seizures or with conditions that potentially lower the seizure threshold.

Elderly patients with dementia
Cariprazine has not been studied in elderly patients with dementia and is not recommended to treat elderly patients with dementia due to increased risk of overall mortality.

Risk of cerebrovascular accidents (CVA)
An approximately 3-fold increased risk of CVA has been seen in randomised placebo controlled clinical studies in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Cariprazine should be used with caution in patients with risk factors for stroke.

Cardiovascular disorders

Blood pressure changes
Cariprazine can cause orthostatic hypotension as well as hypertension (see section 4.8). Cariprazine should be used with caution in patients with known cardiovascular disease predisposing to blood pressure changes. Blood pressure should be monitored.

Electrocardiogram (ECG) changes
QT prolongation can develop in patients treated with antipsychotics.
With cariprazine no QT interval prolongation was detected compared to placebo in a clinical study designed to assess QT prolongation (see section 5.1). In clinical studies, only a few, non-serious, QT- prolongations have been reported with cariprazine (see section 4.8). Therefore, cariprazine should be used cautiously in patients with known cardiovascular disease or in patients with a family history of QT prolongation and in patients treated with medicinal products that might cause QT prolongation (see section 5.1).

Venous thromboembolism (VTE)
Cases of 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 cariprazine and preventive measures undertaken.


Hyperglycaemia and diabetes mellitus
Patients with an established diagnosis of diabetes mellitus or patients with risk factors for diabetes mellitus (e.g. obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should be monitored for serum glucose levels. In clinical studies, glucose-related adverse reactions have been reported with cariprazine (see section 5.1).

Weight change
Significant weight gain has been observed with the use of cariprazine. Patients should have their weight monitored regularly (see section 4.8).

Concomitant treatment with moderate CYP3A4 inhibitors
Co-administration of cariprazine with moderate inhibitors of CYP3A4 may lead to increased total cariprazine exposure. Monitoring of the individual response and tolerability is recommended and, if needed, the cariprazine dose should be (temporarily) reduced to account for the potential increase in exposure (see section 4.5).

Excipients with known effect

Reagila 3, 4.5 and 6 hard capsules contain Allura red AC (E 129), which may cause allergic reactions.

Effects on Driving

     4.7      Effects on ability to drive and use machines

Cariprazine has minor or moderate influence on the ability to drive and use machines. Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy with Reagila does not affect them adversely.