Reagila

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 



 
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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Reagila 1.5 mg hard capsules 
Reagila 3 mg hard capsules 
Reagila 4.5 mg hard capsules 
Reagila 6 mg hard capsules 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Reagila 1.5 mg hard capsules 
 
Each hard capsule contains cariprazine hydrochloride corresponding to 1.5 mg cariprazine. 
 
Reagila 3 mg hard capsules 
 
Each hard capsule contains cariprazine hydrochloride corresponding to 3 mg cariprazine. 
 
Excipients with known effect 
 
Each hard capsule contains 0.0003 mg Allura red AC (E 129). 
 
Reagila 4.5 mg hard capsules 
 
Each hard capsule contains cariprazine hydrochloride corresponding to 4.5 mg cariprazine. 
 
Excipients with known effect 
 
Each hard capsule contains 0.0008 mg Allura red AC (E 129). 
 
Reagila 6 mg hard capsules 
 
Each hard capsule contains cariprazine hydrochloride corresponding to 6 mg cariprazine. 
 
Excipients with known effect 
 
Each hard capsule contains 0.0096 mg Allura red AC (E 129). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Hard capsule 
 
Reagila 1.5 mg hard capsules 
 
‘Size 4’ (approximately 14.3 mm in length) hard gelatin capsule with white opaque cap and white 
opaque body imprinted with “GR 1.5” on the capsule body with black ink. The capsules are filled with 
white to yellowish white powder mixture. 
 
Reagila 3 mg hard capsules 



 
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‘Size 4’ (approximately 14.3 mm in length) hard gelatin capsule with green opaque cap and white 
opaque body imprinted with “GR 3” on the capsule body with black ink. The capsules are filled with 
white to yellowish white powder mixture. 
 
Reagila 4.5 mg hard capsules 
 
‘Size 4’ (approximately 14.3 mm in length) hard gelatin capsule with green opaque cap and green 
opaque body imprinted with “GR 4.5” on the capsule body with white ink. The capsules are filled with 
white to yellowish white powder mixture. 
 
Reagila 6 mg hard capsules 
 
‘Size 3’ (approximately 15.9 mm in length) hard gelatin capsule with purple opaque cap and white 
opaque body imprinted with “GR 6” on the capsule body with black ink. The capsules are filled with 
white to yellowish white powder mixture. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Reagila is indicated for the treatment of schizophrenia in adult patients. 
 
4.2 Posology and method of administration 
 
Posology 
 
The recommended starting dose of cariprazine is 1.5 mg once daily. Thereafter the dose can be 
increased slowly in 1.5 mg increments to a maximum dose of 6 mg/day, if needed. The lowest 
effective dose should be maintained according to the clinical judgement of the treating physician. 
Because of the long half-life of cariprazine and its active metabolites, changes in dose will not be fully 
reflected in plasma for several weeks. Patients should be monitored for adverse reactions and 
treatment response for several weeks after starting cariprazine and after each dosage change (see 
section 5.2). 
 
Switching from other antipsychotics to cariprazine 
When switching from another antipsychotic to cariprazine gradual cross-titration should be 
considered, with gradual discontinuation of the previous treatment while cariprazine treatment is 
initiated. 
 
Switching to another antipsychotic from cariprazine 
When switching to another antipsychotic from cariprazine, no gradual cross-titration is needed, the 
new antipsychotic should be initiated in its lowest dose while cariprazine is discontinued. It should be 
considered that plasma concentration of cariprazine and its active metabolites will decline by 50% in 
~1 week (see section 5.2). 
 
Special population 
 
Renal impairment 
No dose adjustment is required in patients with mild to moderate renal impairment (Creatinine 
Clearance (CrCl) ≥ 30 mL/min and < 89 mL/min). Safety and efficacy of cariprazine have not been 
evaluated in patients with severe renal impairment (CrCl < 30 mL/min). Use of cariprazine is not 
recommended in patients with severe renal impairment (see section 5.2). 
 
Hepatic impairment 
No dose adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh 



 
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score between 5-9). Safety and efficacy of cariprazine have not been evaluated in patients with severe 
hepatic impairment (Child-Pugh score between 10 and 15). Use of cariprazine is not recommended in 
patients with severe hepatic impairment (see section 5.2). 
 
Elderly 
Available data in elderly patients aged ≥65 years treated with cariprazine are not sufficient to 
determine whether or not they respond differently from younger patients (see section 5.2). Dose 
selection for an elderly patient should be more cautious. 
 
Paediatric population 
The safety and efficacy of cariprazine in children and adolescents aged less than 18 years have not 
been established. No data are available. 
 
Method of administration 
 
Reagila is for oral use, to be taken once daily at the same time of the day with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
Concomitant administration of strong or moderate CYP3A4 inhibitors (see section 4.5). 
Concomitant administration of strong or moderate CYP3A4 inducers (see section 4.5). 
 
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 is a frequently occurring adverse reaction 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-EPS medication. 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 



 
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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 neuroleptic malignant syndrome (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 cerebrovascular adverse reactions has been seen in 
randomised placebo controlled clinical trials 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. 
 
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 trial 
designed to assess QT prolongation (see section 5.1). In clinical trials, 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 venous thromboembolism 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. 
 



 
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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 trials, glucose-related adverse 
reactions have been reported with cariprazine (see section 5.1). 
 
Women of childbearing potential 
 
Women of childbearing potential must use highly effective contraception while taking cariprazine and 
at least for 10 weeks after stopping treatment (see sections 4.5 and 4.6). Women using systemically 
acting hormonal contraceptives should add a second barrier method. 
 
Weight change 
 
Significant weight gain has been observed with the use of cariprazine. Patients should have their 
weight monitored regularly (see section 4.8). 
 
Excipients 
 
Reagila 3 mg, 4.5 mg and 6 mg hard capsules contain Allura red AC (E 129), which may cause 
allergic reactions. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Potential for other medicinal products to affect cariprazine 
 
Metabolism of cariprazine and its major active metabolites, desmethyl cariprazine (DCAR) and 
didesmethyl cariprazine (DDCAR), is mediated mainly by CYP3A4 with a minor contribution of 
CYP2D6. 
 
CYP3A4 inhibitors 
Ketoconazole, a strong CYP3A4 inhibitor, caused two fold increase in plasma exposure for total 
cariprazine (sum of cariprazine and its active metabolites) during short-term (4 days) 
co-administration, either if unbound or unbound+bound moieties considered. 
Due to the long half-life of the active moieties of cariprazine a further increase in plasma exposure of 
total cariprazine can be expected during longer co-administration. Therefore, co-administration of 
cariprazine with strong or moderate inhibitors of CYP3A4 (e.g. boceprevir, clarithromycin, cobicistat, 
indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, 
telaprevir, telithromycin, voriconazole, diltiazem, erythromycin, fluconazole verapamil) is 
contraindicated (see section 4.3). Consumption of grapefruit juice should be avoided. 
 
CYP3A4 inducers 
Co-administration of cariprazine with strong and moderate inducers of CYP3A4 may result in a 
significant decrease in total cariprazine exposure, therefore the co-administration of cariprazine and 
strong or moderate CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, St. 
John’s wort (Hypericum perforatum), bosentan, efavirenz, etravirine, modafinil, nafcillin) is 
contraindicated (see section 4.3). 
 
CYP2D6 inhibitors 
CYP2D6 mediated pathway plays a minor role in the metabolism of cariprazine, the major pathway is 
via CYP3A4 (see section 5.2). Therefore CYP2D6 inhibitors are unlikely to have a clinically relevant 
effect on cariprazine metabolism. 
 
Potential for cariprazine to affect other medicinal products 
 
P-glycoprotein (P-gp) substrates 



 
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Cariprazine is a P-gp inhibitor in vitro at its theoretical maximum intestinal concentration. The clinical 
consequences of this effect is not fully understood, however the use of P-gp substrates with narrow 
therapeutic index such as dabigatran and digoxin could require extra monitoring and dose adjustment. 
 
Hormonal contraceptives 
It is currently unknown whether cariprazine may reduce the effectiveness of systemically acting 
hormonal contraceptives, and therefore women using systemically acting hormonal contraceptives 
should add a second barrier method. 
 
Pharmacodynamic interactions 
 
Given the primary central nervous system effects of cariprazine, Reagila should be used with caution 
in combination with other centrally acting medicinal products and alcohol. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/contraception 
 
Women of childbearing potential must be advised to avoid pregnancy while on Reagila. Female 
patients of child-bearing potential must use highly effective contraceptive methods during treatment 
and for at least 10 weeks following the last dose of Reagila. It is currently unknown if cariprazine may 
reduce the effectiveness of systemically acting hormonal contraceptives and therefore women using 
systemically acting hormonal contraceptives should add a barrier method (see section 4.5). 
 
Pregnancy 
 
There are no or limited amount of data from the use of cariprazine in pregnant women. 
Studies in animals have shown reproductive toxicity including developmental malformations in rats 
(see section 5.3). 
 
Reagila is not recommended during pregnancy and in women of childbearing potential not using 
effective contraception. After discontinuation of cariprazine treatment contraception should be used 
for at least 10 weeks due to the slow elimination of active moieties. 
 
Neonates exposed to antipsychotics (including cariprazine) 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. These complications have varied in 
severity; while in some cases symptoms have been self-limited, in other cases, neonates have required 
intensive care unit support and prolonged hospitalization. Consequently, newborns should be 
monitored carefully. 
 
Breast-feeding 
 
It is unknown whether cariprazine or its major active metabolites are excreted in human milk. 
Cariprazine and its metabolites are excreted in milk of rats during lactation (see section 5.3). A risk to 
the newborns/infants cannot be excluded. Breast-feeding should be discontinued during treatment with 
cariprazine. 
 
Fertility 
 
The effect of cariprazine on human fertility has not been evaluated. In rat studies lower female fertility 
and conception indices were observed (see section 5.3). 
 
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 



 
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be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably 
certain that therapy with Reagila does not affect them adversely. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most frequently reported ADRs with cariprazine in the dose range (1.5-6 mg) were akathisia 
(19%) and parkinsonism (17.5%). Most events were mild to moderate in severity. 
 
Tabulated list of adverse reactions 
 
Adverse drug reactions (ADRs) based upon pooled data from cariprazine schizophrenia studies are 
shown by system organ class and by preferred term. 
 
Adverse reactions are ranked by frequency, the most frequent first, using the following convention: 
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), not known (cannot be estimated from the available data). Within 
each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
Adverse drug reactions occurring in patients with schizophrenia 
 
MedDRA 
System 
Organ Class 

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) 

Frequency 
not known 

Blood and 
lymphatic 
system 
disorders 

  Anaemia 
Eosinophilia 

Neutropenia  

Immune 
system 
disorders 

   Hypersensitivi
ty 

 

Endocrine 
disorders 

  Blood thyroid 
stimulating 
hormone 
decreased 

Hypothyroidis
m 

 

Metabolism 
and nutrition 
disorders 

 Weight 
increased 
Decreased 
appetite 
Increased 
appetite 
Dyslipidaemia 

Blood sodium 
abnormal 
Blood glucose 
increased 
Diabetes 
mellitus 

  

Psychiatric 
disorders 

 Sleep 
disorders1 
Anxiety 
 

Suicidal 
behaviour 
Delirium 
Depression 
Libido 
decreased 
Libido 
increased 
Erectile 
dysfunction 

  

Nervous 
system 
disorders 

Akathisia2 
Parkinsonism3 

Sedation 
Dizziness 
Dystonia4 
Other 

Lethargy 
Dysaesthesia 
Dyskinesia6 
Tardive 

Seizures/ 
Convulsion 
Amnesia 
Aphasia 

Neuroleptic 
malignant 
syndrome 



 
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extrapyramidal 
diseases and 
abnormal 
movement 
disorders5 

dyskinesia 

Eye disorders  Vision blurred Eye irritation 
Intraocular 
pressure 
increased 
Accommodati
on disorder 
Visual acuity 
reduced 

Photophobia 
Cataract 

 

Ear and 
labyrinth 
disorders 

  Vertigo   

Cardiac 
disorders 

 Tachyarrhytmi
a 

Cardiac 
conduction 
disorders 
Bradyarrhytmi
a 
Electrocardiog
ram QT 
prolonged 
Electrocardiog
ram T wave 
abnormal  

  

Vascular 
disorders 

 Hypertension 
 

Hypotension   

Respiratory, 
thoracic and 
mediastinal 
disorders 

  Hiccups   

Gastrointesti
nal disorders 

 Nausea 
Constipation 
Vomiting 

Gastrooesopha
geal reflux 
disease 

Dysphagia  

Hepatobiliary 
disorders 

 Hepatic 
enzymes 
increased 
 

Blood 
bilirubin 
increased 
 

 Toxic hepatitis 

Skin and 
subcutaneous 
tissue 
disorders 

  Pruritus 
Rash 

  

Musculoskele
tal and 
connective 
tissue 
disorders 

 Blood creatine 
phosphokinase 
increased 
 

 Rhabdomyoly
sis 

 

Renal and 
urinary 
disorders 

  Dysuria 
Pollakisuria 

  

Pregnancy, 
puerperium 
and perinatal 
conditions 

    Drug 
withdrawal 
syndrome 
neonatal (see 



 
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section 4.6) 
General 
disorders and 
administratio
n site 
conditions 

 Fatigue Thirst   

1Sleep disorders: Insomnia, Abnormal dreams/nightmare, Circadian rhythm sleep disorder, Dyssomnia, 
Hypersomnia, Initial insomnia, Middle insomnia, Nightmare, Sleep disorder, Somnambulism, Terminal 
insomnia 
2Akathisia: Akathisia, Psychomotor hyperactivity, Restlessness 
3Parkinsonism: Akinesia, Bradykinesia, Bradyphrenia, Cogwheel rigidity, Extrapyramidal disorder, Gait 
disturbance, Hypokinesia, Joint stiffness, Tremor, Masked facies, Muscle rigidity, Musculoskeletal stiffness, 
Nuchal rigidity, Parkinsonism 
4Dystonia: Blepharospasm, Dystonia, Muscle tightness, Oromandibular dystonia, Torticollis, Trismus 
5Other extrapyramidal diseases and abnormal movement disorders: Balance disorder, Bruxism, Drooling, 
Dysarthria, Gait deviation, Glabellar reflex abnormal, Hyporeflexia, Movement disorder, Restless legs 
syndrome, Salivary hypersecretion, Tongue movement disturbance 
6Dyskinesia: Choreoathetosis, Dyskinesia, Grimacing, Oculogyric crisis, Protrusion tongue 
 
Description of selected adverse reactions 
 
Lens opacity/Cataract 
Development of cataracts was observed in cariprazine non-clinical studies (see section 5.3). Therefore, 
cataract formation was closely monitored with slit lamp examinations in the clinical studies and 
patients with existing cataracts were excluded. During the schizophrenia clinical development program 
of cariprazine, few cataract cases were reported, characterized with minor lens opacities with no visual 
impairment (13/3192; 0.4%). Some of these patients had confounding factors. The most commonly 
reported ocular adverse event was blurred vision (placebo: 1/683; 0.1%, cariprazine: 22/2048; 1.1%). 
 
Extrapyramidal symptoms (EPS) 
In the short term studies the incidence of EPS was observed in 27%; 11.5%; 30.7% and 15.1% in 
patients treated with cariprazine, placebo, risperidone and aripiprazole respectively. Akathisia was 
reported in 13.6%; 5.1%; 9.3% and 9.9% in patients treated with cariprazine, placebo, risperidone and 
aripiprazole respectively. Parkinsonism was experienced in 13.6%; 5.7%; 22.1% and 5.3% in patients 
treated with cariprazine, placebo, risperidone and aripiprazole respectively. Dystonia was observed in 
1.8%; 0.2%; 3.6% and 0.7% in patients on cariprazine, placebo, risperidone and aripiprazole, 
respectively.  
 
In the placebo-controlled part of the long-term maintenance of effect study EPS was 13.7% in the 
cariprazine group compared to 3.0% in the placebo treated patients. Akathisia was reported in 3.9% in 
patients treated with cariprazine, versus 2.0% in the placebo group. Parkinsonism was experienced in 
7.8% and 1.0% in cariprazine and placebo group respectively.  
 
In the negative symptom study EPS was reported in 14.3% in the cariprazine group and 11.7% in the 
risperidone treated patients. Akathisia was reported in 10.0% in patients treated with cariprazine and 
5.2% in the risperidone group. Parkinsonism was experienced in 5.2% and 7.4% in cariprazine and 
risperidone treated patients respectively. Most EPS cases were mild to moderate in intensity and could 
be handled with common anti-EPS medicinal products. The rate of discontinuation due to EPS related 
ADRs was low. 
 
Venous thromboembolism (VTE) 
Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein 
thrombosis have been reported with antipsychotics - Frequency unknown. 
 
Elevated liver transaminases 
Elevated liver transaminases (ALT, AST) are frequently observed with antipsychotic treatment. In the 
cariprazine clinical studies the incidence of ALT, AST elevation ADRs occurred in 2.2% of 
cariprazine-, 1.6% of risperidone- and 0.4% of placebo-treated patients. None of the cariprazine-



 
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treated patients had any liver damage. 
 
Weight changes 
In the short term studies, there were slightly greater mean increases in body weight in the cariprazine 
group compared to the placebo group; 1 kg and 0.3 kg, respectively. In the long term maintenance of 
effect study, there was no clinically relevant difference in change of body weight from baseline to end 
of treatment (1.1 kg for cariprazine and 0.9 kg for placebo). In the open-label phase of the study 
during 20 weeks cariprazine treatment 9.0% of patients developed potentially clinically significant 
(PCS) weight gain (defined as increase ≥ 7%) while during the double-blind phase, 9.8 % of the 
patients who continued with cariprazine treatment had PCS weight gain versus 7.1% of the patients 
who were randomized to placebo after the 20 week open-label cariprazine treatment. In the negative 
symptom study, the mean change of body weight was -0.3 kg for cariprazine and +0.6 kg for 
risperidone and PCS weight gain was observed in 6% of the cariprazine group while 7.4% of the 
risperidone group.  
 
QT- prolongation 
With cariprazine no QT interval prolongation was detected compared to placebo in a clinical trial 
designed to assess QT prolongation (see section 5.1). In other clinical trials, only a few, non-serious, 
QT-prolongations have been reported with cariprazine. During the long-term, open-label treatment 
period in, 3 patients (0.4%) had QTcB > 500 msec, one of whom also had QTcF > 500 msec. A > 60 
msec increase from baseline was observed in 7 patients (1%) for QTcB and in 2 patients (0.3%) for 
QTcF. In the long-term , maintenance of effect study, during the open-label phase, > 60 msec increase 
of from baseline was observed in 12 patients (1.6%) for QTcB and in 4 patients (0.5%) for QTcF. 
During the double-blind treatment period, > 60 msec increases from baseline in QTcB were observed 
in 3 cariprazine-treated patients (3.1%) and 2 placebo-treated patients (2%). 
 
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 
 
Symptoms 
 
Accidental acute overdose (48 mg/day) was reported in one patient. This patient experienced 
orthostasis and sedation. The patient fully recovered the same day. 
 
Management of overdose 
 
Management of overdose should concentrate on supportive therapy including maintenance of an 
adequate airway, oxygenation and ventilation and management of symptoms. Cardiovascular 
monitoring should commence immediately, including continuous electrocardiographic monitoring for 
possible arrhythmias. In case of severe extrapyramidal symptoms, anticholinergic medicinal products 
should be administered. Since cariprazine is highly bound to plasma proteins, haemodialysis is 
unlikely to be useful in the management of overdose. Close medical supervision and monitoring 
should continue until the patient recovers. 
There is no specific antidote to cariprazine. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Psycholeptics, other antipsychotics, ATC code: N05AX15 



 
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Mechanism of action 
 
The mechanism of action of cariprazine is not fully known. However the therapeutic effect of 
cariprazine may be mediated through a combination of partial agonist activity at dopamine D3, D2 (Ki 
values of 0.085-0.3 nM versus 0.49-0.71 nM respectively) and serotonin 5-HT1A receptors (Ki values 
of 1.4-2.6 nM), and antagonist activity at serotonin 5-HT2B, 5-HT2A and histamine H1 receptors (Ki 
values of 0.58-1.1 nM, 18.8 nM and 23.3 nM, respectively). Cariprazine has low affinity for serotonin 
5-HT2C and adrenergic α1 receptors (Ki values of 134 nM and 155 nM, respectively). Cariprazine has 
no appreciable affinity for cholinergic muscarinic receptors (IC50 > 1000 nM). The two major active 
metabolites, desmethyl cariprazine and didesmethyl cariprazine have a similar in vitro receptor 
binding and functional activity profile as the parent drug. 
 
Pharmacodynamic effects 
 
In vivo non-clinical studies demonstrated that cariprazine occupies D3 receptors to a similar extent as 
D2 receptors at pharmacologically effective doses. There was a dose-dependent occupancy of brain 
dopamine D3 and D2 receptors (with preferential occupancy in regions with higher D3 expression) in 
patients with schizophrenia within the therapeutic dose range of cariprazine for 15 days. 
 
The effects of cariprazine on the QT interval were evaluated in patients with schizophrenia or 
schizoaffective disorder. Holter monitor-derived electrocardiographic assessments were obtained in 
129 patients over a twelve hour period at baseline and steady state. No QT interval prolongation was 
detected following supratherapeutic doses (9 mg/day or 18 mg/day). No patients treated with 
cariprazine experienced QTc increases ≥ 60 msec from baseline, nor did any patient experience a QTc 
of > 500 msec in the study. 
 
Clinical efficacy 
 
Efficacy with short-term use 
The efficacy of cariprazine for the treatment of acute schizophrenia was studied in three multi-center, 
multinational, randomized, double-blind, placebo-controlled 6-week trials including 1,754 patients 
with the age of 18 to 60 years. The primary endpoint was change from baseline to week 6 in the 
Positive and Negative Syndrome Scale (PANSS) total score and the secondary endpoint was change 
from baseline to week 6 in the Clinical Global Impressions-Severity (CGI-S) score in all acute 
schizophrenia studies. In a multinational placebo controlled study using fixed doses of 1.5 mg, 3.0 mg 
and 4.5 mg cariprazine and 4.0 mg risperidone for assay sensitivity, all cariprazine doses and the 
active-control showed statistically significant improvement in both primary as well as secondary 
endpoint compared to placebo. In another multinational placebo controlled study using fixed doses of 
3.0 mg, and 6.0 mg cariprazine and 10 mg aripiprazole for assay sensitivity, both cariprazine doses 
and the active-control showed statistically significant improvement in both primary as well as 
secondary endpoint compared to placebo. In a third multinational placebo controlled study using 
fixed/flexible doses of 3.0-6.0 mg and 6.0-9.0 mg cariprazine, both cariprazine doses groups showed 
statistically significant improvement in both primary as well as secondary endpoint compared to 
placebo. 
Results for the primary outcome parameter are summarized in Table 1 below. Results for the 
secondary outcome parameter (CGI) and additional endpoints were supportive of the primary 
endpoint. 
 
Table 1. Change From Baseline to Week 6 in the PANSS Total Score in Studies of Acute 

Exacerbations of Schizophrenia—ITT Population 

 Baseline Mean ± SD 
Change 
LS mean (SE) 

Treatment difference 
versus placebo (95% 
CI) 

P-value 

PANSS total (MMRM) 
RGH-MD-16 (n=711) 



 
13 

Placebo 97.3 ± 9.22 –13.29 (1.82) — — 
Cariprazine 1.5 mg/day 97.1 ± 9.13 –21.27 (1.77) –7.97 (–12.94, –3.01) 0.0017 
Cariprazine 3 mg/day 97.2 ± 8.66 –21.45 (1.74) –8.16 (–13.09, –3.22) 0.0013 
Cariprazine 4.5 mg/day 96.7 ± 9.01 –23.77 (1.74) –10.48 (–15.41, –5.55) < 0.0001 
Risperidone 4 mg/day 98.1 ± 9.50 –29.27 (1.74) –15.98 (–20.91, –11.04) < 0.0001* 
RGH-MD-04 (n=604) 
Placebo 96.5 ± 9.1 –14.3 (1.5) — — 
Cariprazine 3 mg/day 96.1 ± 8.7 –20.2 (1.5) –6.0 (–10.1, –1.9) 0.0044 
Cariprazine 6 mg/day 95.7 ± 9.4 –23.0 (1.5) –8.8 (–12.9, –4.7) < 0.0001 
Aripiprazole 10 mg/day 95.6 ± 9.0 –21.2 (1.4) –7.0 (–11.0, –2.9) 0.0008* 
RGH-MD-05 (n=439) 
Placebo 96.6 ± 9.3 –16.0 (1.6) — — 
Cariprazine 3 to 6 mg/day 96.3 ± 9.3 –22.8 (1.6) –6.8 (–11.3, –2.4) 0.0029 
Cariprazine 6 to 9 mg/day 96.3 ± 9.0 –25.9 (1.7) –9.9 (–14.5, –5.3) < 0.0001 
CI = confidence interval; ITT = intent to treat; LS mean = least squares mean; PANSS = Positive and 
Negative Syndrome Scale. 
*compared to placebo 
 
Efficacy with long-term use 
The efficacy of cariprazine for maintaining antipsychotic effect was investigated in a randomized-
withdrawal, long-term clinical study. Totally, 751 patients with acute symptoms of schizophrenia 
received cariprazine 3-9 mg/day for 20 weeks, of whom 337 received cariprazine in the dose-range of 
3 or 6 mg/day. Stabilized patients were then randomised to receive fixed doses of 3 or 6 mg 
cariprazine (n=51) or placebo (n=51) in a double-blind manner for up to 72 weeks. The primary 
outcome of the study was time to relapse. By the end of the trial 49.0% of placebo-treated patients 
versus 21.6% of cariprazine-treated patients had a relapse of schizophrenic symptoms. Time to relapse 
(92 vs. 326 days-based on the 25th percentile) was therefore significantly longer in the cariprazine 
group than in the placebo group (p=0.009). 
 
Efficacy in predominantly negative symptoms of schizophrenia 
The efficacy of cariprazine for the treatment of predominantly negative symptoms of schizophrenia 
was investigated in a 26-week, multi-centre, double-blind, and active-controlled clinical trial. 
Cariprazine (dose range 3-6 mg, target dose 4.5 mg) was investigated compared to risperidone (dose 
range 3-6 mg, target dose 4 mg) in patients with persistent, predominant negative symptoms of 
schizophrenia (n=461). 86% of patients were less than 55 years old, 54% of them were male. 
 
Persistent predominant negative symptoms were defined as symptoms lasting for a period of at least 
6 months with high level of negative symptoms and low level of positive symptoms [(PANSS factor 
score for negative symptoms ≥ 24, a score of ≥ 4 on a minimum 2 of the 3 PANSS items (N1: flat 
affect, N4: avolition, and N6: poverty of speech) and PANSS factor score for positive symptoms 
≤ 19]. Patients with secondary negative symptoms, such as moderate to severe depressive symptoms 
and clinically relevant parkinsonism (EPS) were excluded. 
 
Both cariprazine- and risperidone-treated patient groups have shown statistically significant 
improvement in the change from baseline for the primary efficacy parameter, PANSS factor score for 
negative symptoms (PANSS-FSNS) (p< 0.001). However, a statistically significant difference 
(p=0.002) in favour of cariprazine over risperidone was observed from Week 14 onward (Table 2). 
Both cariprazine- and risperidone-treated patient groups have shown statistically significant 
improvement in the change from baseline for the secondary efficacy parameter, Personal and Social 
Performance (PSP) total score (p< 0.001). However, a statistically significant difference (p< 0.001) in 
favour of cariprazine over risperidone was observed from Week 10 onward (Table 2). 
Differences on the Clinical Global Impression Severity (p=0.005) and Improvement (p<0.001) scales, 
as well as PANSS-FSNS response rates (PANSS FSNS ≥ 30% improvement at Week 26; p= 0.003) 



 
14 

were supportive of findings on the primary and secondary efficacy parameters. 
 
Table 2 Summary of results in study RGH-188-005 
 

 
Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
cariprazine in paediatric population. See section 4.2 for information on paediatric use. 
 
5.2 Pharmacokinetic properties 
 
Cariprazine has two pharmacologically active metabolites with similar activites as cariprazine, 
desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). Total cariprazine (sum of 
cariprazine + DCAR and DDCAR) exposure approaches 50% of steady state exposure in ~1 week of 
daily dosing while 90% of steady state is achieved in 3 weeks. At steady state, exposure to DDCAR is 
approximately two to three-fold higher than to cariprazine, and exposure to DCAR is approximately 
30% of cariprazine exposure. 
 
Absorption 
 
Absolute bioavailability of cariprazine is unknown. Cariprazine is well absorbed after oral 
administration. Following multiple-dose administration, peak plasma concentrations for cariprazine 
and the major active metabolites generally occur at approximately 3-8 hours post dose. 
Administration of a single dose of 1.5 mg cariprazine with a high-fat meal (900 to 1,000 calories) did 
not significantly affect the Cmax or AUC of cariprazine (AUC0-∞ increased by 12%, Cmax decreased by 
< 5% under fed condition versus fasting). The effect of food on the exposure of the metabolites DCAR 
and DDCAR was also minimal. 
Cariprazine can be administered with or without food. 
 
Distribution 
 
Based on a population pharmacokinetic analysis, the apparent volume of distribution (V/F) was 916 L 
for cariprazine, 475 L for DCAR and 1,568 L for DDCAR, indicating extensive distribution of 
cariprazine and its major active metabolites. Cariprazine and its major active metabolites are highly 
bound (96 to 97% for CAR, 94% to 97% for DCAR and 92% to 97% for DDCAR) to plasma proteins. 
 
Biotransformation 
 
The metabolism of cariprazine involves demethylation (DCAR and DDCAR), hydroxylation (hydroxy 
cariprazine, HCAR) and a combination of demethylation and hydroxylation (hydroxy desmethyl 
cariprazine, HDCAR and hydroxy didesmethyl cariprazine, HDDCAR). The metabolites of HCAR, 
HDCAR, and HDDCAR are subsequently biotransformed to their corresponding sulfate and 
glucuronide conjugates. An additional metabolite, desdichlorophenyl piperazine cariprazine 
(DDCPPCAR) acid, is produced by dealkylation and subsequent oxidation of cariprazine. 

Efficacy parameter Cariprazine 
LS mean 

Risperidone 
LS mean 

Estimated 
Treatment 
Difference 

95%CI p-value 

PANSS-FSNS at Baseline 27.8 27.5 - - - 
PANSS-FSNS at Week 26 18.5 19.6 - - - 
PANSS-FSNS CfB to 
Week 26 

-8.9 -7.4 -1.5 -2,4; -
0.5 

0.002 

Total PSP at Baseline 48.8 48.2 - - - 
Total PSP at Week 26 64.0 59.7 - - - 
Total PSP CfB to Week 26 14.3 9.7 4.6 2.7; 6.6 <0.001 
CfB= change from baseline 



 
15 

Cariprazine is metabolized by CYP3A4 and, to a lesser extent, by CYP2D6, to DCAR and HCAR. 
DCAR is further metabolized by CYP3A4 and to a lesser extent by CYP2D6 into DDCAR and 
HDCAR. DDCAR is further metabolised to HDDCAR by CYP3A4. 
 
Cariprazine and its major active metabolites are not substrates of P-glycoprotein (P-gp), the organic 
anion transporting polypeptide 1B1 and 1B3 (OATP1B1 and OATP1B3), and the breast cancer 
resistance protein (BCRP). This suggests that an interaction of cariprazine with inhibitors of P-gp, 
OATP1B1, OATP1B3 and BCRP is unlikely. 
 
Elimination 
 
Elimination of cariprazine and its major active metabolites is mainly through hepatic metabolism. 
Following administration of 12.5 mg/day cariprazine to patients with schizophrenia, 20.8% of the dose 
was excreted in urine as cariprazine and its metabolites. 
Unchanged cariprazine is excreted by 1.2% of the dose in urine and 3.7% of the dose in feces. 
 
The mean terminal half-life (1 to 3 days for cariprazine and DCAR and 13 to 19 days for DDCAR) is 
not predictive of time to reach steady state or plasma concentration decline after treatment 
discontinuation. For the management of patients treated with cariprazine, the effective half-life is more 
relevant than the terminal half-life. The effective (functional) half-life is ~ 2 days for cariprazine and 
DCAR, 8 days for DDCAR and is ~1 week for total cariprazine. The plasma concentration of total 
cariprazine will gradually decline following dose discontinuation or interruption. The plasma 
concentration of total cariprazine decreases by 50% in ~1 week and greater than 90% decline in total 
cariprazine concentration occurs in ~3 weeks. 
 
Linearity 
 
After repeated administration plasma exposure of cariprazine and its two major active metabolites, 
desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), increases proportionally over 
the therapeutic dose range of 1.5 to 6 mg. 
 
Special populations 
 
Renal impairment 
Population pharmacokinetic modelling was performed using data from patients enrolled in the 
schizophrenia cariprazine clinical program with differing levels of renal function, including normal 
renal function (creatinine clearance (CrCl) ≥ 90 mL/min), as well as mild (CrCl 60 to 89 mL/min) and 
moderate (CrCl 30 to 59 mL/min) renal impairment. No significant relationship was found between 
cariprazine plasma clearance and creatinine clearance. 
Cariprazine has not been evaluated in patients with severe (CrCl < 30 mL/min) renal impairment (see 
section 4.2). 
 
Hepatic impairment 
A 2-part study (a single dose of 1 mg cariprazine [Part A] and a daily dose of 0.5 mg cariprazine for 
14 days [Part B] was conducted in patients with varying degrees of impaired hepatic function (Child-
Pugh Classes A and B). Compared to healthy subjects, patients with either mild or moderate hepatic 
impairment had up to approximately 25% higher exposure (Cmax and AUC) for cariprazine and up to 
approximately 45% lower exposure for the major active metabolites, desmethyl cariprazine and 
didesmethyl cariprazine, following the single dose of 1 mg cariprazine or 0.5 mg cariprazine for 
14 days. 
The total active moiety (CAR+DCAR+DDCAR) exposure (AUC and Cmax) decreased by 21-22% and 
13-15% in mild or moderate hepatic impairment (HI), respectively, compared to healthy subjects if 
unbound + bound concentrations were considered, while for unbound total moiety a decrease of 12-
13% and an increase of 20-25% were calculated in mild HI patients and in moderate HI patients, 
respectively, after multiple dosing of cariprazine. 
Cariprazine has not been evaluated in patients with severe hepatic impairment (Child-Pugh Class C) 
(see section 4.2). 



 
16 

 
Age, gender and race 
In the population PK analysis there were no clinically relevant differences in the PK parameters (AUC 
and Cmax of the sum of cariprazine and its major active metabolites) based on age, gender and race. 
This analysis included 2,844 patients of different races, involving 536 patients between the ages of 50 
and 65. Of the 2,844 patients 933 were female (see section 4.2). In elderly patients above 65 years of 
age data are limited. 
 
Smoking status 
Because cariprazine is not a substrate for CYP1A2, smoking is not expected to have an effect on the 
pharmacokinetics of cariprazine. 
 
Potential for cariprazine to affect other medicinal products 
 
Cariprazine and its major active metabolites did not induce CYP1A2, CYP2B6 and CYP3A4 enzymes 
and were not inhibitors of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP219, CYP2D6, 
CYP2E1 and CYP3A4 in vitro. Cariprazine and its major active metabolites are not inhibitors of 
transporters OATP1B1, OATP1B3, BCRP, organic cation transporter 2 (OCT2), and organic anion 
transporters 1 and 3 (OAT1 and OAT3) in vitro. DCAR and DDCAR were not inhibitors of 
transporter P-gp although cariprazine was a P-gp inhibitor in the intestine (see section 4.5). 
 
5.3 Preclinical safety data 
 
Cariprazine caused bilateral cataract and secondary retinal changes (retinal detachment and cystic 
degeneration) in the dog. The exposure (AUC of total cariprazine) at the no-observed-adverse-effect-
level (NOAEL) for ocular toxicity is 4.2-fold the clinical AUC exposure at the maximal recommended 
human dose (MRHD) of 6 mg/day. Increased incidence of retinal degeneration/atrophy was observed 
in albino rats in the 2-year study at clinically relevant exposures. 
 
Phospholipidosis was observed in the lungs of rats, dogs, and mice (with or without inflammation) and 
in the adrenal gland cortex of dogs at clinically relevant exposures. Inflammation was observed in the 
lungs of dogs dosed for 1 year with a NOAEL at AUC exposures 2.7 (males) and 1.7 (females) times 
the clinical exposure at the MRHD. No inflammation was observed at the end of 2-month drug-free 
period at an exposure 4.2 times the clinical exposure at the MRHD; however, inflammation was still 
present at higher doses. 
 
Hypertrophy of the adrenal gland cortex was observed at 4.1 times the clinical exposure at the MRHD 
in rats (females only) and at clinically relevant total cariprazine plasma concentrations in mice. In 
dogs, reversible hypertrophy/hyperplasia and vacuolation/vesiculation of the adrenal gland cortex 
were observed with a NOAEL 4.2 times the clinical exposure at the MRHD. 
 
In female rats, lower fertility and conception indices were observed at clinically relevant exposures 
based on mg/m2 body surface area. No effects on male fertility were noted at exposures up to 4.8 times 
the clinical exposure at the MRHD. 
 
Administration of cariprazine to rats during the period of organogenesis caused malformations, lower 
pup survival, and developmental delays at drug exposures less than the human exposure at the MRHD 
of 6 mg/day. In rabbits, cariprazine caused maternal toxicity, but no foetal toxicity at exposures 
5.8 times the clinical exposure at the MRHD. 
 
Administration of cariprazine to pregnant rats during the period of organogenesis, throughout 
pregnancy and lactation at clinically relevant exposures decreased postnatal survival, birth weight, and 
post-weaning body weight of first generation pups. In addition, pale, cold bodies and developmental 
delays (renal papillae not developed/underdeveloped and decreased auditory startle response in males) 
were observed in the absence of maternal toxicity. Reproductive performance of the first generation 
pups was unaffected; however, second generation pups also had similar clinical signs and lower body 
weight. 



 
17 

 
Cariprazine and its metabolites were excreted in milk of rats during lactation. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Capsule contents 
 
Pregelatinized (maize) starch 
Magnesium stearate 
 
Capsule shell (1.5 mg capsule) 
 
Titanium dioxide (E 171) 
Gelatin 
 
Capsule shell (3 mg capsule) 
 
Allura red AC (E 129) 
Brilliant blue FCF (E 133) 
Titanium dioxide (E 171) 
Yellow iron oxide (E 172) 
Gelatin 
 
Capsule shell (4.5 mg capsule) 
 
Allura red AC (E 129) 
Brilliant blue FCF (E 133) 
Titanium dioxide (E 171) 
Yellow iron oxide (E 172) 
Gelatin 
 
Capsule shell (6 mg capsule) 
 
Brilliant blue FCF (E 133) 
Allura red AC (E 129) 
Titanium dioxide (E 171) 
Gelatin 
 
Printing ink (black: 1.5 mg, 3 mg and 6 mg capsules) 
 
Shellac 
Black iron oxide (E 172) 
Propylene glycol 
Potassium hydroxide 
 
Printing ink (white: 4.5 mg capsule) 
 
Shellac 
Titanium dioxide (E 171) 
Propylene glycol 
Simeticone 
 
6.2 Incompatibilities 
 



 
18 

Not applicable. 
 
6.3 Shelf life 
 
5 years 
 
6.4 Special precautions for storage 
 
Keep the blister in the outer carton in order to protect from light. 
This medicinal product does not require any special temperature storage conditions. 
 
6.5 Nature and contents of container 
 
Transparent hard PVC/PE/PVDC blister heat-sealed with hard aluminium foil backing packed in 
folded carton box. 
 
Reagila 1.5 mg and Reagila 3 mg hard capsules 
 
Cartons contain 7, 14, 21, 28, 30, 49, 56, 60, 84, 90 or 98 hard capsules. 
 
Reagila 4.5 mg and Reagila 6 mg hard capsules 
 
Cartons contain 21, 28, 30, 49, 56, 60, 84, 90 or 98 hard capsules. 
 
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 
 
Gedeon Richter Plc. 
Gyömrői út 19-21. 
1103 Budapest 
Hungary 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1209/001-040 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
13 July 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 



 
19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX II 

 
A. MANUFACTURER 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 

 



 
20 

 
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Gedeon Richter Plc. 
Gyömrői út 19-21 
1103 Budapest 
HUNGARY 
 
 
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  
 
The requirements for submission of periodic safety update reports 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. 
 
The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk Management Plan (RMP) 

 
The 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.  

 
 



 
21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



 
22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 
23 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
folded carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Reagila 1.5 mg hard capsules 
cariprazine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains cariprazine hydrochloride corresponding to 1.5 mg cariprazine. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
7 hard capsules 
14 hard capsules 
21 hard capsules 
28 hard capsules 
30 hard capsules 
49 hard capsules 
56 hard capsules 
60 hard capsules 
84 hard capsules 
90 hard capsules 
98 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use. 
 
 
QR code to be included 
www.reagila.com 
 
 
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. 
 
 



 
24 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the blister in the outer carton in order to protect from light. 
 
 
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 
 
Gedeon Richter Plc. 
Gyömrői út 19-21. 
1103 Budapest, Hungary 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1209/001-010  {7x,14x,28x,30x,49x,56x,60x,84x,90x,98x} 
EU/1/17/1209/037   {21x} 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
reagila 1.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.* 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



 
25 

 
PC: 
SN: 
NN: 



 
26 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
blisterfoil 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Reagila 1.5 mg hard capsules 
cariprazine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Gedeon Richter Plc. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
 



 
27 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
folded carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Reagila 3 mg hard capsules 
cariprazine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains cariprazine hydrochloride corresponding to 3 mg cariprazine. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains Allura red AC (E129). See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
7 hard capsules 
14 hard capsules 
21 hard capsules 
28 hard capsules 
30 hard capsules 
49 hard capsules 
56 hard capsules 
60 hard capsules 
84 hard capsules 
90 hard capsules 
98 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use. 
 
 
QR code to be included 
www.reagila.com 
 
 
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. 



 
28 

 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the blister in the outer carton in order to protect from light. 
 
 
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 
 
Gedeon Richter Plc. 
Gyömrői út 19-21. 
1103 Budapest, Hungary 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1209/011-020  {7x,14x,28x,30x,49x,56x,60x,84x,90x,98x} 
EU/1/17/1209/038   {21x} 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
reagila 3 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.* 



 
29 

 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



 
30 

 
 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
blisterfoil 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Reagila 3 mg hard capsules 
cariprazine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Gedeon Richter Plc. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
 



 
31 

 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
folded carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Reagila 4.5 mg hard capsules 
cariprazine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains cariprazine hydrochloride corresponding to 4.5 mg cariprazine. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains Allura red AC (E129). See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
21 hard capsules 
28 hard capsules 
30 hard capsules 
49 hard capsules 
56 hard capsules 
60 hard capsules 
84 hard capsules 
90 hard capsules 
98 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use. 
 
 
QR code to be included 
www.reagila.com 
 
 
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. 
 



 
32 

 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the blister in the outer carton in order to protect from light. 
 
 
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 
 
Gedeon Richter Plc. 
Gyömrői út 19-21. 
1103 Budapest, Hungary 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1209/021-028  {28x,30x,49x,56x,60x,84x,90x,98x} 
EU/1/17/1209/039   {21x} 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
reagila 4.5 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.* 
 
 



 
33 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



 
34 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
blisterfoil 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Reagila 4.5 mg hard capsules 
cariprazine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Gedeon Richter Plc. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
 



 
35 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
folded carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Reagila 6 mg hard capsules 
cariprazine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each hard capsule contains cariprazine hydrochloride corresponding to 6 mg cariprazine. 
 
 
3. LIST OF EXCIPIENTS 
 
Also contains Allura red AC (E129). See the package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Hard capsule 
 
21 hard capsules 
28 hard capsules 
30 hard capsules 
49 hard capsules 
56 hard capsules 
60 hard capsules 
84 hard capsules 
90 hard capsules 
98 hard capsules 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Oral use. 
 
 
QR code to be included 
www.reagila.com 
 
 
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. 
 
 



 
36 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the blister in the outer carton in order to protect from light. 
 
 
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 
 
Gedeon Richter Plc. 
Gyömrői út 19-21. 
1103 Budapest, Hungary 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1209/029-036  {28x,30x,49x,56x,60x,84x,90x,98x} 
EU/1/17/1209/040   {21x} 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
reagila 6 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included.* 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 



 
37 

 
PC: 
SN: 
NN: 



 
38 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
blisterfoil 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Reagila 6 mg hard capsules 
cariprazine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Gedeon Richter Plc. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
 



 
39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 
40 

 
 

Package leaflet: Information for the user 
 

Reagila 1.5 mg hard capsules 
Reagila 3 mg hard capsules 

Reagila 4.5 mg hard capsules 
Reagila 6 mg hard capsules 

 
cariprazine 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
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. This includes any possible side effects not listed 

in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Reagila is and what it is used for 
2. What you need to know before you take Reagila 
3. How to take Reagila 
4. Possible side effects 
5. How to store Reagila 
6. Contents of the pack and other information 
 
 
1. What Reagila is and what it is used for 
 
Reagila contains the active substance cariprazine and belongs to a group of medicines called 
antipsychotics. It is used to treat adults with schizophrenia. 
Schizophrenia is a disease characterised by symptoms such as hearing, seeing or sensing things which 
are not there (hallucination), suspiciousness, mistaken beliefs, incoherent speech and behaviour and 
emotional flatness. People with this condition may also feel depressed, guilty, anxious, tense, or not 
being able to start or keep up planned activities, unwillingness to speak, lack of emotional response to 
a situation that would normally stimulate feelings in others. 
 
 
2. What you need to know before you take Reagila 
 
Do not take Reagila: 
- if you are allergic to cariprazine or any of the other ingredients of this medicine (listed in 

section 6). 
- if you are taking medicines used to treat: 

- hepatitis caused by the hepatitis C virus (medicines containing boceprevir and telaprevir) 
- bacterial infections (medicines containing clarithromycin, telithromycin, erythromycin 

and nafcillin) 
- tuberculosis (medicines containing rifampicin) 
- HIV infections (medicines containing cobicistat, indinavir, nelfinavir, ritonavir, 

saquinavir, efavirenz and etravirine) 
- fungal infections (medicines containing itraconazole, posaconazole, voriconazole and 



 
41 

fluconazole) 
- Cushing’s syndrome - when the body produces an excess of cortisol (medicines 

containing ketoconazole) 
- depression (herbal therapy containing St. John's wort (Hypericum perforatum) and 

medicines containing nefazodone) 
- epilepsy and seizures (medicines containing carbamazepine, phenobarbital and 

phenytoin) 
- heart disease (medicines containing diltiazem and verapamil) 
- sleepiness (medicines containing modafinil) 
- high blood pressure in the lungs (medicines containing bosentan). 

 
Warnings and precautions 
Tell your doctor immediately: 
- if you are having any thoughts or feelings about hurting yourself or to commit suicide. Suicidal 

thoughts and behaviours are more likely at the beginning of the treatment. 
- if you experience a combination of fever, sweating, faster breathing, muscle stiffness and 

drowsiness or sleepiness (may be signs of neuroleptic malignant syndrome). 
 
Talk to your doctor or pharmacist before taking Reagila, or during treatment if you have: 
- ever experienced or start to experience restlessness and inability to sit still. These symptoms 

may occur early during treatment with Reagila. Tell your doctor if this happens. 
- ever experienced or start to experience abnormal, involuntary movements, most commonly of 

the tongue or face. Tell your doctor if this happens. 
- visual impairment. Your doctor will advise you to visit an ophthalmologist. 
- irregular heart beat or if someone else in your family has a history of irregular heart beat 

(including so called QT prolongation seen with ECG monitoring), and tell your doctor if you are 
taking other medicines, because they might cause or worsen this ECG change. 

- high or low blood pressure, cardiovascular disease. Your doctor will need to check your blood 
pressure regularly. 

- dizziness on standing up due to a drop in your blood pressure, which may cause fainting 
- a history of blood clots, or if someone else in your family has a history of blood clots, as 

medicines for schizophrenia have been associated with formation of blood clots 
- a history of stroke, especially if you are elderly or know that you have other risk factors for 

stroke. Tell your doctor immediately if you notice any signs of a stroke. 
- dementia (loss of memory and other mental abilities) especially if you are elderly 
- Parkinson’s disease 
- if you have diabetes or risk factors for diabetes (e.g. obesity, or someone else in your family has 

diabetes). Your doctor will need to check your blood sugar regularly since it may be increased 
by Reagila. Signs of high blood sugar level are excessive thirst, passing of large amounts of 
urine, increase in appetite and feeling weak. 

- a history of seizures (fits) or epilepsy. 
 
Weigth increase 
Reagila may cause significant weight increase which may affect your health. Your doctor will 
therefore check your weight regularly. 
 
Contraception 
Women of childbearing potential must use highly effective contraception while taking Reagila and for 
at least 10 weeks after stopping treatment. If you are using hormonal contraceptives a so-called barrier 
method (e.g.condom or diaphragma) should also be used. (See section “Pregnancy and breast-
feeding”). 
 
Children and adolescents 
This medicine is not recommended for children and adolescents under 18 years due to the lack of data 
in these patients. 
 
Other medicines and Reagila 



 
42 

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. You cannot take certain medicines together with Reagila (see section “Do not take 
Reagila”). 
 
Taking Reagila together with some medicines may require a dose adjustment of Reagila or the other 
medicine. These are medicines used to treat heart diseases containing digoxin, blood thinners 
containing dabigatran, or medicines affecting your mental functions. 
If you are using hormonal contraceptives a so-called barrier method should also be used (see section 
“Pregnancy and breast-feeding” below). 
 
Reagila with food, drink and alcohol 
You should not drink grapefruit juice during treatment with Reagila. 
Alcohol should be avoided when taking Reagila. 
 
Pregnancy and breast-feeding 
 
Women of childbearing potential 
 
Women of childbearing potential must use effective contraception during Reagila treatment. Even 
after treatment is stopped, contraception must be used for at least 10 weeks after your last dose of 
Reagila. This is because the medicine will stay in your body for some time after the last dose was 
taken. If you are using hormonal contraceptives a so-called barrier method(e.g. condom or diaphragm) 
should also be used. Ask your doctor about appropriate choices of contraception. 
 
Pregnancy 
 
Do not take this medicine during pregnancy unless your doctor has told you to do so. 
 
If your doctor decides that you should take this medicine during pregnancy, your doctor will monitor 
your baby closely after birth. This is because the following symptoms may occur in newborn babies of 
mothers who have used this medicine 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 should contact your doctor. 
 
Breast-feeding 
 
Do not breast-feed if you are taking Reagila because a risk for the baby cannot be excluded. Contact 
your doctor for advice.  
 
Driving and using machines 
There is a minor or moderate risk that the medicine could affect the ability to drive and use machines. 
Drowsiness, dizziness and vision problems may occur during treatment with this medicine (see section 
4). Do not drive or use any tools or machines until you know that this medicine does not affect you in 
a negative way. 
 
Reagila 3 mg, 4.5 mg, 6 mg hard capsules contain Allura red AC (E129). 
Allura red AC is a coloring agent, which may cause allergic reactions. 
 
 
3. How to take Reagila 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure. 
 
The recommended starting dose is 1.5 mg once a day by mouth. Thereafter, the dose may be slowly 
adjusted by your doctor, in steps of 1.5 mg, depending on how the treatment works for you. 



 
43 

The maximum dose should not exceed 6 mg once a day. 
 
Take Reagila at the same time each day with or without food. 
 
If you were taking another medicine to treat schizophrenia before starting Reagila, your doctor will 
decide whether to stop the other medicine gradually or immediately and how to adjust the dose of 
Reagila. Your doctor will also inform you how to act if you switch from Reagila to another medicine. 
 
Patients with kidney or liver problems 
If you have serious kidney or liver problems Reagila may not be appropriate for you. Talk to your 
doctor. 
 
Elderly patients 
Your doctor will carefully select the appropriate dose for your needs. 
Reagila should not be used by elderly patients with dementia (loss of memory). 
 
If you take more Reagila than you should 
If you have taken more Reagila than your doctor has recommended or if, for example, a child has 
taken it by mistake, contact your doctor or go to the nearest hospital right away and take the pack of 
the medicine with you. You may experience dizziness from low blood pressure, or have abnormal 
heartbeats, you may feel sleepy, tired, or have abnormal body movements and find it difficult to stand 
or walk. 
 
If you forget to take Reagila 
If you forget to take a dose, take it as soon as you remember it. However, if it is almost time for your 
next dose, skip the missed dose and continue as usual. 
Do not take a double dose to make up for a forgotten dose. 
If you miss two or more doses, contact your doctor. 
 
If you stop taking Reagila 
If you stop taking this medicine you will lose the effects of the medicine. Even if you feel better, do 
not alter or stop your daily dose of Reagila unless told to do so by your doctor as your symptoms may 
return. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor immediately if you have: 
- a severe allergic reaction seen as fever, swollen mouth, face, lip or tongue, shortness of breath, 

itching, skin rash and sometimes a drop in blood pressure. (Rare side effect) 
- combination of fever, sweating, muscle stiffness, and drowsiness or sleepiness. These can be the 

signs of the so-called neuroleptic malignant syndrome. (Side effect with frequency not known 
- inexplicable muscle pains, muscle cramps or muscle weakness. These may be signs of muscle 

damage which can cause very serious kidney problems.  (Rare side effect) 
- symptoms related to 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. (Side effect with frequency not known) 

- thoughts or feelings about hurting yourself or to commit suicide, suicide attempt. (Uncommon 
side effect) 

 
Other side effects 
 
Very common side effects (may affect more than 1 in 10 people) 



 
44 

 
- feeling of restlessness and inability to sit still 
- Parkinsonism - a medical condition with many various symptoms which include decreased or 

slow movements, slowness of thought, jerks when bending the limbs (cogwheel rigidity), 
shuffling, steps, shaking, little or no facial expression, muscle stiffness, drooling 

 
Common side effects (may affect up to 1 in 10 people) 
 
- anxiety 
- sleepiness, difficulty in sleeping, abnormal dreams, nightmare, sleepwalking 
- dizziness 
- involuntary twisting movements and strange postures 
- excessive teeth grinding or jaw clenching, drooling, persistent blinking in response to tapping of 

the forehead (an abnormal reflex), movement problems, tongue movement disturbance (these 
are called extrapyramidal symptoms) 

- blurred vision 
- high blood pressure 
- fast, irregular heartbeat 
- decreased or increased appetite 
- nausea, vomiting, constipation 
- weight increased 
- tiredness 
- the following can be seen in laboratory tests: 

° increases in liver enzymes 
° increases in the level of creatine phosphokinase in the blood 
° abnormal amount of lipids (e.g. cholesterol and/or fat) in the blood 

 
Uncommon side effects (may affect up to 1 in 100 people) 
 
- depression 
- sudden and severe confusion 
- spinning sensation 
- unpleasant, abnormal sense of touch 
- drowsiness, lack of energy or a lack of interest in doing things 
- involuntary movements, most commonly of the tongue or face. This can appear after short or 

long term use. 
- decreased or increased sexual desire, erectile problems 
- eye irritation, high pressure in the eye, poor vision 
- focusing problems seeing at a distance to or seeing close-to 
- low blood pressure 
- abnormal ECG reading, abnormal nerve impulses in the heart 
- slow, irregular heart rate 
- hiccups 
- heartburn 
- thirst 
- pain when passing urine 
- abnormally frequent and large urinations 
- itching, rash 
- diabetes 
- the following can be seen in laboratory tests: 

° abnormal sodium level in the blood 
° increased blood glucose (blood sugar), increased bile pigment (bilirubin) in the blood 
° anaemia (reduced levels of red blood cells) 
° increase in a type of white blood cells 
° decreased level of thyroid stimulating hormone (TSH) in the blood 

 



 
45 

Rare side effects (may affect up to 1 in 1,000 people) 
 
- seizure 
- loss of memory, loss of speech 
- eye discomfort in bright light 
- clouding of the lens in the eye leading to a decrease in vision (cataract) 
- difficulty in swallowing 
- reduced levels of a type of white blood cells, this can make you more susceptible to infections 
- underactive thyroid gland 
 
Side effects with not known frequency (frequency cannot be estimated from the available data) 
- inflammation of the liver (pain in the upper right abdomen, yellowing of the eye and skin, 

weakness, fever) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor. 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 Reagila 
 
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 the blister after EXP. 
The expiry date refers to the last day of that month. 
 
Keep the blister in the outer carton in order to protect from light. 
This medicine does not require any special temperature storage conditions. 
 
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 Reagila contains 
 
- The active substance is cariprazine. 

Reagila 1.5 mg: Each hard capsule contains cariprazine hydrochloride corresponding to 1.5 mg 
cariprazine. 
Reagila 3 mg: Each hard capsule contains cariprazine hydrochloride corresponding to 3 mg 
cariprazine. 
Reagila 4.5 mg: Each hard capsule contains cariprazine hydrochloride corresponding to 4.5 mg 
cariprazine. 
Reagila 6 mg: Each hard capsule contains cariprazine hydrochloride corresponding to 6 mg 
cariprazine. 

 
- The other ingredients are: 

Reagila 1.5 mg hard capsules: pregelatinized (maize) starch, magnesium stearate, titanium 
dioxide (E 171), gelatin, black ink (shellac, black iron oxide (E 172), propylene glycol, 
potassium hydroxide). 

 
Reagila 3 mg hard capsules: pregelatinized (maize) starch, magnesium stearate, allura red AC 
(E 129), brilliant blue FCF (E 133), titanium dioxide (E 171), yellow iron oxide (E 172), gelatin, 
black ink (shellac, black iron oxide (E 172), propylene glycol, potassium hydroxide). 

 



 
46 

Reagila 4.5 mg hard capsules: pregelatinized (maize) starch, magnesium stearate, allura red AC 
(E 129), brilliant blue FCF (E 133), titanium dioxide (E 171), yellow iron oxide (E 172), gelatin, 
white ink (shellac, titanium dioxide (E 171), propylene glycol, simeticone). 

 
Reagila 6 mg hard capsules: pregelatinized (maize) starch, magnesium stearate, brilliant blue 
FCF (E 133), allura red AC (E 129), titanium dioxide (E 171), gelatin, black ink (shellac, black 
iron oxide (E 172), propylene glycol, potassium hydroxide). 

 
What Reagila looks like and contents of the pack 
 
- Reagila 1.5 mg hard capsules: ‘Size 4’ (approximately 14.3 mm in length) hard gelatin capsule 

with white opaque cap and white opaque body imprinted with “GR 1.5” on the capsule body 
with black ink. The capsules are filled with white to yellowish white powder. 

 
- Reagila 3 mg hard capsules: ‘Size 4’ (approximately 14.3 mm in length) hard gelatin capsule 

with green opaque cap and white opaque body imprinted with “GR 3” on the capsule body with 
black ink. The capsules are filled with white to yellowish white powder. 

 
- Reagila 4.5 mg hard capsules: ‘Size 4’ (approximately 14.3 mm in length) hard gelatin capsule 

with green opaque cap and green opaque body imprinted with “GR 4.5” on the capsule body 
with white ink. The capsules are filled with white to yellowish white powder. 

 
- Reagila 6 mg hard capsules: ‘Size 3’ (approximately 15.9 mm in length) hard gelatin capsule 

with purple opaque cap and white opaque body imprinted with “GR 6” on the capsule body with 
black ink. The capsules are filled with white to yellowish white powder. 

 
The capsules are packed in transparent hard PVC/PE/PVDC blister heat-sealed with hard aluminium 
foil backing. The blisters are packed in a folded carton box. 
 
Reagila 1.5 mg and Reagila 3 mg hard capsules are available in pack sizes containing 7, 14, 21, 28, 30, 
49, 56, 60, 84, 90 or 98 hard capsules. 
 
Reagila 4.5 mg and Reagila 6 mg hard capsules are available in pack sizes containing 21, 28, 30, 49, 
56, 60, 84, 90 or 98 hard capsules. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Gedeon Richter Plc. 
Gyömrői út 19-21 
1103 Budapest 
Hungary 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Recordati BVBA 
Tél/Tel: +32 2 46101 36 
 

Lietuva 
Gedeon Richter Plc. atstovybė Lietuvoje 
Tel: +370 5 261 01 54 
 

България 
ТП „Гедеон Рихтер АД” 
Teл.: + 359 2 8129063 
 

Luxembourg/Luxemburg 
Recordati BVBA 
Tél/Tel: + 32 2 46101 36 (Belgique/Belgien) 
 



 
47 

Česká republika 
Gedeon Richter Marketing ČR, s.r.o. 
Tel: +420 261 141 200 
 

Magyarország 
Richter Gedeon Nyrt. 
Tel.: +36 1 505 7032 
 

Danmark 
Recordati AB 
Tlf: +46 8 545 80 230 (Sverige) 
 

Malta 
Recordati Ireland Limited 
Tel: + 353 21 4379400 (Ireland) 
 

Deutschland 
Recordati Pharma GMBH 
Tel: + 49 731 70470 
 

Nederland 
Recordati BVBA 
Tel: + 32 2 46101 36 (België) 
 

Eesti 
Richter Gedeon Eesti filiaal 
Tel: +372 608 5301 
 

Norge 
Recordati AB 
Tlf: + 46 8 545 80 230 (Sverige) 
 

Ελλάδα 
Recordati Hellas Pharmaceuticals S.A. 
Τηλ: + 30 210-6773822 
 

Österreich 
Recordati Pharma GMBH 
Tel: + 49 731 70470 (Deutschland) 
 

España 
Casen Recordati S.L. 
Tel: + 34 91 659 15 50 
 

Polska 
GEDEON RICHTER POLSKA Sp. z o.o. 
Tel.: + 48 (22)755 96 48 
 

France 
Bouchara-Recordati S.A.S. 
Tél: + 33 1 45 19 10 00 
 

Portugal 
Jaba Recordati S.A. 
Tel: + 351 21 432 95 00 
 

Hrvatska 
Gedeon Richter Croatia d.o.o. 
Tel: + 385 1 5625 712 
 
Ireland 
Recordati Ireland Limited 
Tel: + 353 21 4379400 
 

România 
Gedeon Richter România S.A. 
Tel: +40-265-257 011 
 
Slovenija 
Gedeon Richter d.o.o. 
Tel: + +386 8 205 68 70 
 

Ísland 
Recordati AB 
Sími: +46 8 545 80 230 (Svíþjóð) 
 

Slovenská republika 
Gedeon Richter Slovakia, s.r.o. 
Tel: +421 2 5020 5801 
 

Italia 
RECORDATI S.p.A. 
Tel: + 39 02 487871 
 

Suomi/Finland 
Recordati AB 
Puh/Tel: +46 8 545 80 230 (Ruotsi/Sverige) 
 

Κύπρος 
Recordati Hellas Pharmaceuticals S.A. 
Τηλ: + 30 210-6773822 (Ελλάδα) 
 

Sverige 
Recordati AB 
Tel: +46 8 545 80 230 
 

Latvija 
Gedeon Richter Plc. pārstāvniecība Latvijā 
Tel: +371 67845338 
 

United Kingdom 
Recordati Pharmaceuticals Ltd. 
Tel: + 44 1491 576336 
 

 
This leaflet was last revised in <{MM/YYYY}>  
 
Other sources of information 
Detailed and updated information on this medicine is available by scanning the QR code below and 



 
48 

the outer carton with a smartphone. 
The same information is also available on the following URL: www.reagila.com 
 
‘QR code to be included’ + www.reagila.com 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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

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    /ENU (Use these settings to create Adobe PDF documents best suited for high-quality prepress printing.  Created PDF documents can be opened with Acrobat and Adobe Reader 5.0 and later.)
  >>
  /Namespace [
    (Adobe)
    (Common)
    (1.0)
  ]
  /OtherNamespaces [
    <<
      /AsReaderSpreads false
      /CropImagesToFrames true
      /ErrorControl /WarnAndContinue
      /FlattenerIgnoreSpreadOverrides false
      /IncludeGuidesGrids false
      /IncludeNonPrinting false
      /IncludeSlug false
      /Namespace [
        (Adobe)
        (InDesign)
        (4.0)
      ]
      /OmitPlacedBitmaps false
      /OmitPlacedEPS false
      /OmitPlacedPDF false
      /SimulateOverprint /Legacy
    >>
    <<
      /AddBleedMarks false
      /AddColorBars false
      /AddCropMarks false
      /AddPageInfo false
      /AddRegMarks false
      /ConvertColors /ConvertToCMYK
      /DestinationProfileName ()
      /DestinationProfileSelector /DocumentCMYK
      /Downsample16BitImages true
      /FlattenerPreset <<
        /PresetSelector /MediumResolution
      >>
      /FormElements false
      /GenerateStructure false
      /IncludeBookmarks false
      /IncludeHyperlinks false
      /IncludeInteractive false
      /IncludeLayers false
      /IncludeProfiles false
      /MultimediaHandling /UseObjectSettings
      /Namespace [
        (Adobe)
        (CreativeSuite)
        (2.0)
      ]
      /PDFXOutputIntentProfileSelector /DocumentCMYK
      /PreserveEditing true
      /UntaggedCMYKHandling /LeaveUntagged
      /UntaggedRGBHandling /UseDocumentProfile
      /UseDocumentBleed false
    >>
  ]
>> setdistillerparams
<<
  /HWResolution [2400 2400]
  /PageSize [612.000 792.000]
>> setpagedevice