Table 4.
Description of the clozapine-related fatalities’ cases reported to the EudraVigilance (EV) dataset (2005–June 2018). F: female; M: male.
| Clozapine Dosage (mg) | Concomitant Drugs | Medical History | Reactions according to the MedDRA Dictionary (Preferred Terms-PT) | ||
|---|---|---|---|---|---|
| 1 | M, Adult (30 yy) | 200 mg | Benzodiazepines Alcohol | Intentional product misuse; Antipsychotic drug level increased (clozapine plasmatic 1.1 mg/mL); Blood pressure decreased; Loss of consciousness; Poisoning; Dysarthria; Loss of consciousness; Blood alcohol increased | |
| 2 | M, Adult (48 yy) | N/A | Cocaine Opioids Z-drugs |
Hypertension; Schizophrenia; Chronic obstructive pulmonary disease; Arteriosclerosis |
Substance abuse; Toxicity to various agents |
| 3 | M, Adult (25 yy) | 300 mg | Benzodiazepines Opioids |
Cardiac arrest; Arrhythmia Toxicity to various agents (methadone and clozapine); Drug abuse; Drug level increased (methadone and clozapine) |
|
| 4 | M, Adult (44 yy) | N/A | Opioids | Hypertension; Alcoholism; Depression; Epigastric discomfort; Anxiety |
Pulmonary embolism; Drug abuse |
| 5 | M, Adult | 400 mg | Alcohol | Liver function test abnormal; Blood alkaline phosphatase increased; Gamma-glutamyl transferase increased; Asphyxia; Alcohol abuse; Drug abuse (heroin) |
|
| 6 | M, Adult (24yy) | N/A | Alcohol | Anemia | Drug abuse (Clozaril abuse) |
| 7 | F | 300 mg | Alcoholism; Mental impairment; Depression; Treatment noncompliance; Deep vein thrombosis |
Death; Withdrawal syndrome; Acute psychosis; Cognitive disorder; Amnesia; Speech disorder; Gait disturbance; Chills |
|
| 8 | F, Adult (54yy) | 350 mg | Benzodiazepines | Withdrawal syndrome; Insomnia; Completed suicide | |
| 9 | M, Adult (66 yy) | N/A | Completed suicide; Drug abuse | ||
| 10 | F, Adult (25yy) | N/A | Antidepressants | Completed suicide; Drug abuse | |
| 11. | M, Adult (31yy) | N/A | Completed suicide; Drug abuse | ||
| 12 | M | N/A | Obesity; Gastroesophageal reflux; Drug abuse | Drug abuse; Death | |
| 13 | F | N/A | Cocaine Benzodiazepines Opioids |
Drug dependence | Drug abuse (cocaine, leponex and probably benzodiazepines); Death; Hyperthermia malignant; Cardiac arrest; Circulatory collapse; Delirium |
| 14 | M | N/A | Hepatitis | Drug abuse (possible use of non-prescribed drugs); Death | |
| 15 | M | N/A | Salivary hypersecretion; Drug abuse (crack cocaine, marijuana, alcohol); Extrapyramidal disorder |
Nonspecific reaction; Treatment noncompliance; Drug abuse (mixed polysubstance abuse); Death |
|
| 16 | F | N/A | Mood stabilizers Antipsychotics |
Drug abuse | |
| 17 | M | 1000 mg | Hypercholesterolemia; Substance abuse; Hypertension; Schizophrenia; Gastro-esophageal reflux disease |
Hematemesis; Drug abuse; Cardiac arrest; Completed suicide; Toxicity to various agents; Intentional overdose; Resuscitation; Seizure; Tachycardia |
|
| 18 | F, Adult (27yy) | N/A | Drug abuse | ||
| 19 | M, Adult (30yy) | N/A | Myocardial infarction; Drug abuse; Eye swelling; Glossodynia; Tongue coated; Swollen tongue |
||
| 20 | F | N/A | Intentional self-injury; Meningioma; Drug abuse; Hypoglycemia; Peripheral venous disease; Hepatic steatosis; Scar; Pneumonia; Bronchitis; Arteriosclerosis coronary artery; Purulent discharge; Pulmonary congestion; Death |
||
| 21 | M, Adult (26yy) | 800 mg | Coronary artery disease; Drug abuse; Hallucination, auditory; Epilepsy; Depressed mood | ||
| 22 | M, Adult (31yy) | N/A | Death; Substance abuse | ||
| 23 | M | N/A | Surgery; Intentional self-injury; Bipolar disorder | Agitation; Death; Drug abuse; Suicidal ideation; Nasal septum deviation |
|
| 24 | M, Adult (30yy) | N/A | Autonomic nervous system imbalance; Catatonia; Drug withdrawal syndrome; Dyskinesia; Neuroleptic malignant syndrome; Psychotic disorder |
||
| 25 | M, Adult (36yy) | N/A | Alcohol abuse; Drug abuse; Myocardial infarction; Coronary artery disease |
||
| 26 | M | 200 mg | Drug abuse; Obesity | ||
| 27 | M, Adult (34yy) | 350 mg | Circulatory collapse; Intentional product misuse; Cardiopulmonary failure |
||
| 28 | M, Adult (33yy) | N/A | Benzodiazepines Opioids |
Death; Drug abuse (heroin, temazepam) | |
| 29 | N/A | Arm amputation; Drug dependence (including cannabis, benzodiazepines and heroin); Limb reduction defect; Alcohol use | Drug abuse; Loss of consciousness; Hypothermia | ||
| 30 | M, Adult (31yy) | N/A | Abnormal behavior; Myocardial infarction; Drug abuse (heroin, cocaine); Psychomotor hyperactivity; Peripheral coldness; Unresponsive to stimuli; Arteriosclerosis coronary artery; Blood glucose decreased |
||
| 31. | F, Adult (72yy) | 200 mg | Opioids | Schizophrenia; Depression; Somnolence; Anxiety | Movement disorder; Sudden death; Drug abuse |
| 32. | M, Adult (27yy) | 400 mg | Antipsychotics | Asthma; Nicotine dependence; Drug abuse; Obesity; Substance use; Diabetes mellitus; Mental disorder; Alcohol use | Asphyxia; Substance abuse |
| 33. | M, Adult (50 yy) | 550 mg | Hypoxic-ischemic encephalopathy; Drug abuse (cocaine); Pulmonary hemosiderosis; Pulmonary edema; Cardiac arrest; Left ventricular hypertrophy; Arteriosclerosis coronary artery; Aortic arteriosclerosis; Myocardial fibrosis; Hepatic steatosis; Spleen congestion |
||
| 34. | M, Adult (29yy) | 1000 mg | Opioids | Schizophrenia | Substance abuse (heroin) |
| 35. | F, Adult | N/A | Antidepressants | Drug abuse | |
| 36. | M, Adult (34yy) | 700 mg | Schizophrenia; Nicotine dependence; Drug abuse |
Cardiac arrest; Substance abuse | |
| 37. | F, Adult (28yy) | N/A | Antidepressants | Drug abuse | |
| 38. | M | 100 mg | Blood cholesterol increased; Bipolar disorder; Gastroesophageal reflux; Schizoaffective disorder; Diabetes mellitus | Sudden death; Drug abuse (cocaine and another illicit drug) | |
| 39. | F, Adult (50yy) | N/A | Alcohol | Drug abuse; Drug dependence | Completed suicide; Toxicity to various agents; Drug abuse (propofol) |
| 40. | M | N/A | Product use issue; Psychotic disorder | Product use issue; Drug level increased (clozapine levels in the 600,000 s); Death; Adverse event; Psychotic disorder; Intentional product misuse |
|
| 41. | M | N/A | Drug withdrawal syndrome; Memory impairment; Disorientation; Completed suicide |
||
| 42. | F, Adult (28yy) | N/A | Antidepressants | Toxicity to various agents; Drug abuse | |
| 43. | M, Adult (31yy) | 700 mg | Anxiety; Psychotic disorder; Depression | Completed suicide (suicide due to overdose on clozapine); Intentional product misuse; Overdose; Adverse event |
|
| 44. | M | N/A | Completed suicide (patient jumped to his death); Withdrawal syndrome (periodically he would refrain from taking the medication, thus suffering withdrawal/Initially withdrawal symptoms would consist of disorientation after 2–3 days and memory impairment after 4–7 days) | ||
| 45. | M | N/A | Death; Withdrawal syndrome (withdrawal symptoms from the capsule form of Clozaril antipsychotic medication) | ||
| 46. | M, Adult (58yy) | 100 mg | Alcohol use; Hypertension | Drug abuse; Vomiting; Asphyxia; Prescription drug used without a prescription (abuse of clozapine 100 mg tablets) |