Rare and very rare adverse effects of clozapine

Figures & data

Table 1 Adverse reactions divided by frequency regarding patients and treatment: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (<1/10,000), and not known (cannot be estimated from the available data) (Agenzia Italiana del Farmaco [AIFA] document 06/06/2014)²⁵

Type and frequency	Clinical description
Hemic/lymphatic
Common	Leukopenia/decreased WBC/neutropenia/eosinophilia/leukocytosis
Uncommon	Agranulocytosis
Rare	Anemia
Very rare	Thrombocytosis, thrombocytopenia
Metabolic and nutritional
Common	Weight gain
Rare	Diabetes mellitus/hyperglycemia
Very rare	Ketoacidosis/severe hyperglycemia/hypercholesterolemia/hypertriglyceridemia
Psychiatric
Common	Dysarthria
Uncommon	Dysphonia
Rare	Restlessness/agitation
Central nervous system
Very common	Drowsiness/sedation/vertigo
Common	Epileptiform movements/myoclonic jerks/extrapyramidal symptoms/akathisia/tremors/rigidity/headache
Uncommon	Neuroleptic malignant syndrome
Rare	Confusion/delirium
Very rare	Tardive dyskinesia/obsessive–compulsive symptoms
Ocular
Common	Visual disturbances
Cardiovascular
Very common	Tachycardia
Common	Hypertension/hypotension/syncope/ECG-cardiac abnormalities
Rare	Thromboembolism/arrythmia/myocarditis/pericarditis/pericardial effusion
Very rare	Cardiac arrest/cardiomyopathy
Unknown	Myocardial infarction/chest pain/angina
Respiratory
Rare	Aspiration/pneumonia-like symptoms
Very rare	Respiratory failure
Unknown	Nasal congestion
Gastrointestinal
Very common	Nausea/vomiting/anorexia/dry mouth
Common	Dysphagia
Rare	Intestinal obstruction/paralytic ileus/fecal
Very rare	Impaction/swelling of salivary gland
Unknown	Diarrhea/abdominal distention/nervous stomach/abnormal stools
Hepatic
Common	Elevations in liver function tests
Rare	Pancreatitis/hepatitis/cholestatic
Very rare	Hepatic necrosis
Unknown	Hepatic steatosis/hepatic fibrosis/hepatic cirrhosis/hepatotoxicity
Dermatologic
Common	Pruritus/pallor/eczema/erythema/petechiae
Rare	Vasculite/erythema multiforme/Stevens
Very rare	Johnson syndrome, pityriasis rosea
Musculoskeletal
Unknown	Muscle weakness/muscle spasm/muscle pain
Urogenital
Common	Urinary abnormalities
Very rare	Priapism/interstitial nephritis
Unknown	Renal failure/nocturnal enuresis
Other
Common	Hyperthermia malignant/weakness/fever
Very rare	Sudden death/CPK increases

Abbreviations: WBC, white blood cell; ECG, electrocardiogram; CPK, creatine phosphoKinase.

Table 2 Death due to clozapine-associated gastrointestinal hypomotility

Patient (sex, age [years])	Presentation	CLZ dose (mg/day)	Reference
M, 29	Aspiration of vomit secondary to obstruction of the transverse colon	400	Hayes and Gibler^Citation40
F, 31	Large bowel obstruction with mucosal necrosis, pulmonary edema, and shock	300	Thèret et al^Citation96
M, 49	Intermittent indigestion, nausea, chest pain, and vomiting. Collapsed with pulmonary edema secondary to inhalation of feculent vomit	500	Drew and Herdson^Citation97
M, 36	Necrotizing colitis	600	Shammi and Remington^Citation98
M, 43	History of ulcerative esophagitis. Abdominal pain, feculent vomiting, and severe fecal impaction with large intestinal necrosis	–	Levin et al^Citation99
M, 44	Found dead. evidence of pulmonary edema, paralytic ileus, and gastroenteritis	–	Ferslew et al^Citation100
F, 47	Large bowel infarct	–	Flanagan et al^Citation101

Note: –Data unavailable.

Abbreviations: CLZ, clozapine; M, male; F, female.

Farmaciemedici.it [homepage on the Internet]A.I.F.A. [updated June 6, 2014] Available from: http://www.farmaciemedici.it/farmaci/bugiardino/leponex/aifa/Accessed February 19, 2015

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