agranulocytosis , diabetic ketoacidosis , gastrointestinal hypomotility , and myocarditis are well - known adverse effects of clozapine , which are sometimes life threatening . here
a male patient , 36  years , with elevated creatinine kinase levels ( 9899  u / l ) , developed rhabdomyolysis afterafter admission to the emergency department .
approximately 24  h earlier he had intoxicated himself with his maintenance oral medication clozapine 125  mg , temazepam 20  mg and lorazepam 1.5  mg . co - medications , and physical and laboratory examinations did not reveal other risk factors for rhabdomyolysis .
according to the naranjo probability scale there was a probable relation between clozapine dose and symptoms , that developed approximately 24  h after the auto - intoxication of 125  mg tablets . at day 5 of hospitalization
, clozapine and creatinine kinase levels returned to normal and the patient was discharged with no somatic sequelae .
elevated creatinine kinase levels in acute clozapine intoxication may be an indicator that rhabdomyolysis may be involved .
rhabdomyolysis may occur upon an acute overdose of clozapine.elevated creatinine kinase levels in acute clozapine overdose may be associated with the development of rhabdomyolysis.rhabdomyolysis with elevated clozapine and creatinine kinase levels may be reversible .
clozapine is an atypical antipsychotic drug that is used in patients who have not responded adequately to treatment with standard drug treatments for schizophrenia .
its use is limited by agranulocytosis , a rare but potentially life - threatening adverse event .
a 36-year - old man with a history of schizophrenia was admitted to the emergency department of our hospital because of altered consciousness and disorientation . according to the patient and his accompanying brother ,
he had intoxicated himself in the previous 24  h with his current maintenance medication , i.e. , clozapine 125  mg , temazepam 20  mg , and lorazepam 1.5  mg , all prescribed once daily .
he was known for excessive smoking and alcohol ingestion ( an estimated intake of 15 units daily ) .
he was tachycardic with a pulse of 145/min , blood pressure of 166/109  mmhg , and a respiration rate of 22/min .
serum creatinine kinase ( ck ) 9899  u / l , aspartate aminotransferase 305  u / l , alanine aminotransferase 59  u / l , and lactate dehydrogenase 417  u / l were elevated .
arterial blood gas analysis showed an elevated ph 7.49 , po2 3.9  kpa , pco2 18.2  kpa , and bicarbonate 22  mmol / l .
urine analyses for amphetamines , cocaine , methadone , opioids , and cannabis were negative .
chest x - ray and computed tomography scan of the brain were both normal . the initial treatment consisted of 1  l of normal saline in 1  h , an additional 100  ml of sodium bicarbonate 8.4  % , followed by 4  l of normal saline in the next 6 h , for rhabdomyolysis , thiamine 100  mg intramuscularly for chronic alcohol abuse , and lorazepam 1  mg intravenously for agitation and ethanol withdrawal symptoms .
approximately 10  h after arrival at the emergency department , analysis revealed extremely high plasma clozapine concentrations of 3177  g / l ( reference values : 200600  g / l ) , and normal concentrations of temazepam and lorazepam of 0.19  mg / l ( reference values : 0.100.80  mg / l ) and 0.14  mg / l ( reference values : 0.020.25 
the clozapine plasma concentration decreased to non - toxic concentrations ( 153  g / l ) 5  days after hospitalization ( fig .  1 ) .
1patient clozapine and creatinine kinase ( ck ) concentrations during 5  days of hospitalization patient clozapine and creatinine kinase ( ck ) concentrations during 5  days of hospitalization clozapine is an antipsychotic drug with potentially harmful adverse effects .
the most frequently reported symptoms in clozapine intoxication are impaired alertness and tachycardia . also known , but scarcely reported , are extremely high ck levels and rhabdomyolysis .
another cause of rhabdomyolysis in relation to clozapine is a neuroleptic malignant syndrome , a potentially life - threatening but rare condition occurring in psychiatric patients receiving neuroleptic agents .
however , our patient showed no hyperthermia or muscle rigidity and did not meet the diagnostic and statistical manual of mental disorders - fourth edition criteria .
furthermore , the co - medication of temazepam and lorazepam is not likely to be associated with rhabdomyolysis because these agents have no clinically relevant interaction with clozapine ; benzodiazepines solely have been described to be related to this side effect .
however , in the present case , the immobilization secondary to the clozapine overdose and delirium tremens due to alcohol abstinence can not be excluded as contributing factors to the development or augmentation of rhabdomyolysis . according to the naranjo probability scale
, there was a probable relationship , i.e. , score 6 , between the development of rhabdomyolysis and clozapine overdose in this patient .
this score was calculated from the results of previous conclusive reports on the reaction ( + 1 ) , appearance after the drug was given ( + 2 ) , improvement on discontinuation ( + 1 ) , alternative causes ( 1 ) , toxic concentrations ( + 1 ) , reaction less severe when exposure decreased ( + 1 ) , and confirmation of the adverse event by objective evidence , i.e. , manifest rhabdomyolysis and elevated concentrations ( + 1 ) . in conclusion , when ck levels are elevated in patients treated for an overdose with clozapine , rhabdomyolysis should be considered .
frank g. a. jansman , heleen a. crommelin , freek j. a. h. van hout , and jan meulenbelt declare that they have no conflict of interest .
no financial support was received for the conduct of this study or preparation of this manuscript .
a copy of the written consent is available for review by the editor - in - chief of this journal .
 contextclozapine is used for decennia for the treatment of schizophrenia . 
 agranulocytosis , diabetic ketoacidosis , gastrointestinal hypomotility , and myocarditis are well - known adverse effects of clozapine , which are sometimes life threatening . here 
 we report a case of rhabdomyolysis upon an acute overdose of clozapine.casea male patient , 36  years , with elevated creatinine kinase levels ( 9899  u / l ) , developed rhabdomyolysis afterafter admission to the emergency department . 
 approximately 24  h earlier he had intoxicated himself with his maintenance oral medication clozapine 125  mg , temazepam 20  mg and lorazepam 1.5  mg . co - medications , and physical and laboratory examinations did not reveal other risk factors for rhabdomyolysis . 
 according to the naranjo probability scale there was a probable relation between clozapine dose and symptoms , that developed approximately 24  h after the auto - intoxication of 125  mg tablets . at day 5 of hospitalization 
 , clozapine and creatinine kinase levels returned to normal and the patient was discharged with no somatic sequelae.conclusionselevated creatinine kinase levels in acute clozapine intoxication may be an indicator that rhabdomyolysis may be involved . 
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