Table 2.

Some common problems associated with clozapine use and recommended actions

Observation	Possible cause	Possible consequences of inaction	Action required
Clozapine not taken for >48 hours	Non-adherence	Possibility of fatal hypotension if recommenced on same dose or if too rapid re-titration	Repeat clozapine initiation protocol
	Failure in FBC testing
	Failure of supply
	Medical emergency
Raised temperature, flu-like symptoms	Neutropenia/agranulocytosis	Life-threatening infection	Urgent FBC, CRP, troponin and echocardiogram. Consider hospital admission. Consider prophylactic antibiotics
	Pneumonia	Life-threatening infection
	Myocarditis	Heart failure
	Cardiomyopathy
Low WCC/neutrophil count	Impending agranulocytosis	Life-threatening infection	Urgent FBC, troponin and echocardiogram. Consider hospital admission. Consider prophylactic antibiotics
	Sample taken in the morning	Inappropriate break in treatment	Re-do FBC noting time of sample collection
Low blood pressure	Recent non-adherence	Possibility of fatal hypotension	Review and re-initiate clozapine if necessary
	Clozapine dose too high	Possibility of fatal hypotension	Cautious dose reduction
Gastrointestinal hypomotility/constipation	Laxatives not prescribed or not taken	Life-threatening ileus, peritonitis, toxic megacolon	Review dose and laxative regime – if severe stop clozapine and urgent hospital referral
	Stopped smoking
Dysphagia	Clozapine dose too high	Choking	Measure plasma clozapine and adjust dose as necessary
Akathisia	Clozapine dose too high	Increased risk of convulsions, constipation, etc.	Measure plasma clozapine and adjust dose as necessary
Severe sialorrhoea	Dose too high	Bronchopneumonia Relapse due to non-adherence	Review dose and consider adjunct drug treatment
Relapse	Non-adherence	Self-harm Fatal hypotension if normal clozapine dose given	Measure plasma clozapine and adjust dose as necessary
	Started smoking/passive exposure to cigarette smoke	Self-harm	Caution patient as to the effect of smoking on the response to clozapine. Measure plasma clozapine and adjust dose as necessary
	Substance misuse	Self-harm. Fatal poisoning from illicit substances	Substance misuse assessment
Lowered plasma clozapine	Poor adherence	Loss of response	Counsel patient as to the dangers of not taking clozapine as prescribed
	Started smoking	Loss of response	Review dose. Counsel patient as to the dangers of smoking while taking clozapine
Poor/no response	Clozapine ineffective or poorly effective even if taken as prescribed (6–12 months)	Inappropriate risk of clozapine AEs	Review dose and exposure to cigarette smoke. Ensure adherence by plasma clozapine measurement. Consider augmentation strategies