■ Fatal cases where a causal relationship with XEPLION is unknown have been reported during the period of early phase pharmacovigilance. As of April 15th 2014, 14 fatal cases have been granted permission to disclose by the reporting physicians as follows.

No ADR Age Gen Pre-administration of XEPLION Latency Medical history Concomitant （MedDRA PT） der Paliperidone or Dose antipsychotic(s) Risperidone/Dose (At first injection)

Aripiprazole tablet, Risperidone sustained-release 1 Death 50s F 100 mg 3 days Constipation Quetiapine fumarate suspension for injection/50mg tablet

Pulmonary embolism Right ventricular failure Risperidone sustained-release Hyperuricaemia, 2 50s M 150 mg 41 days Olanzapine tablet Rhabdomyolysis suspension for injection/50mg Hepatic steatosis Psychiatric symptom

Risperidone sustained-release Quetiapine fumarate 3 Death 60s M 25 mg 14 days Unknown suspension for injection/25mg tablet Hepatitis C, Risperidone sustained-release Hypertension, 4 Death 50s M 75 mg 40 days Zotepine tablet suspension for injection/25mg Abnormal hepatic function

Acute myocardial Risperidone oral solution Hyperuricaemia, Aripiprazole tablet, 5 30s M 150 mg 4 days infarction /4mg Obesity Olanzapine tablet

Death, Palpitations Hyperglycaemia, 6 50s M None 50 mg 13 days Olanzapine tablet Dyspnoea, Dysarthria Asthma, Back pain

Hypothermia Risperidone sustained-release 7 40s M 50 mg 42 days Hyperuricaemia Risperidone tablet Stress fracture suspension for injection/25mg

Haloperidol decanoate Mild mental injection, Olanzapine 8 Death 30s M None 150 mg 14 days retardation tablet, Blonanserin tablet

Olanzapine tablet, Quetiapine fumarate Risperidone sustained-release Hypotension, 9 Myocardial infarction 60s F 150 mg 34 days tablet, suspension for injection/50mg Arrhythmia Levomepromazine maleate tablet

Insomnia, Asphyxia, Vomiting Risperidone oral 10 50s F None 150 mg 19 days Restlessness, Cerebrovascular accident solution Diabetes mellitus

Hypertension， Risperidone tablet/9mg， Obesity, Diabetes Paliperidone Paliperidone extended-release 11 Death 50s M 150 mg 43 days mellitus, extended-release tablet, tablet/12mg Extrapyramidal Risperidone tablet (continued after start of XEPLION) disorder

Risperidone Aspiration 12 Death 40s M 150 mg 77 days None (Unknown formulation) pneumonia

Multi-organ failure 13 50s F None 150 mg 107 days Pneumonia, Ileus None Abnormal hepatic function

Risperidone oral solution, Haloperidol Risperidone oral solution/2mg 14 Pneumonia 70s M 150 mg 36 days None injection, Haloperidol (as needed basis) oral solution, Olanzapine tablet Underline：events leading to outcome of death

■ Death case details

Patient Adverse drug reaction Indication Daily dose Gender/Age （Medical (number of doses) Clinical course and treatment history） M/40s Schizophrenia 150 mg History of present illness and past medical history of diabetes mellitus: None （Aspiration (once) Approximately 1 year Since around this time, the patient had experienced ） 100 mg Pneumonia before administration repeated episodes of aspiration pneumonia and had (once) been hospitalized for aggravated aspiration pneumonia. 50 mg The patient's physical condition was poor. (twice) Risperidone had been administered in the previous treatment. Start of administration The patient was transferred from another hospital to the reporter's hospital for the aspiration pneumonia. Treatment with XEPLION 150 mg was started because the patient was unable to take oral drugs. 7 days after Treatment with XEPLION 100 mg was administered. 35 days after Treatment with XEPLION 50 mg was administered. 36 days after Abnormal blood sugar level developed. The laboratory data were unknown. The patient received 20% glucose solution. 63 days after Treatment with XEPLION 50 mg was administered. No extrapyramidal symptom (EPS) developed after XEPLION had been initiated. 77 days after (onset) The patient died. Cause of death: Unknown. Autopsy: Not performed. Electrocardiogram: No abnormalities. Renal function, hepatic function, and cardiac function: No abnormalities. Drug dependence: None. Concomitant drug(s): Sodium valproate, Flunitrazepam

Patient Adverse drug reaction Indication Daily dose Gender/Age （Medical (number of doses) Clinical course and treatment history） F/50s Schizophrenia 150 mg The patient did not have chronic hepatitis. （Pneumonia, （4 times） Unknown The patient was transferred from another hospital to the Ileus） 100 mg reporter's hospital for ileus. The patient's condition had （once） been complicated by pneumonia.

Start of administration Treatment with XEPLION 150 mg was started. 7 days after XEPLION 100 mg was administered. 35 days after XEPLION 150 mg was administered. 63 days after XEPLION 150 mg was administered. Unknown Pedal oedema was observed during treatment with XEPLION. Unknown The pedal oedema improved with diuretic drugs. 91 days after XEPLION 150 mg was administered. No EPS developed after XEPLION had been initiated. 100 days after Abnormal hepatic function developed. GOT: 1890 IU/L GPT: 1330 IU/L 107 days after (onset) The patient died of multi-organ failure during the hospitalization. Renal function and cardiac function: No abnormalities Autopsy: Not performed. Concomitant drug(s): Piperacillin sodium, Pantethine, Lansoprazole, Cefotiam hydrochloride, Kampo products