Community Clozapine Monitoring Protocols: Review of vital sign monitoring requirements in supporting the first two days of community clozapine initiation

  • Kane Christian Larson University of British Columbia Faculty of Pharmacy


The study took data from sites that were following guidelines implemented prior to August 2016 and examined available patient charts for monitoring data. Temperature, respiration rate, and pulse have a distinct peak centred around 4 hours with a range of 3-6 hours. The temperature did not rise above 38˚C in any of the patients (N=43) between pre-dose and 6hours post dose (for days 1 and 2). Heart rate and the temperature had a greater increase on the second day.  It is important to monitor temperature as fever is a risk factor for agranulocytosis and Neuroleptic Malignant Syndrome (NMS). Temperature elevation (>38˚C) is associated to have a peak incidence within the first three weeks of treatment. However, it is usually benign and self-limiting. Therefore, elevation of temperature is not a good reason to stop therapy when examining just that parameter.

When examining the effects of clozapine on heart rate elevation is that it may be a risk factor for myocarditis and cardiomyopathy. However, the reports of myocarditis are rare and tachycardia (bpm >100) occurs in 25% of all patient. Most commonly, monitoring heart rate is used to assess compliance and mild elevations of pulse is not significant enough to discontinue therapy.

When examining the average respiratory rate, the rate did not increase by more than one breath/minute in day 1 or day 2. When monitoring breathing rate, the primary concern is oversedation and respiratory collapse. However, it is rare to occur but, should be monitored closely when benzodiazepines are involved or other central nervous system depressants.

Blood pressure monitoring is the most significant vital to measure during clozapine initiation. Orthostatic hypotension has a 9% incidence and is dose-related. Also, orthostatic hypotension is most likely to occur during the initial dose titration. Approximately 1:3000 patients experience collapse and respiratory/cardiac arrest when on clozapine.  The most significant blood pressure change occurred on the second day (dose dependent). For example, the blood pressure changes ranged from an increase of 39mmHg  to a decrease of 39 mmHg. Thus, blood pressure varied quite considerably. Due to the high incidence of orthostatic hypertension and considerable blood pressure fluctuations, it is of particular importance to measure blood pressure over any other parameter during the first two days of a clozapine start.

Heart rate also had the most significant change on the second day (dose-dependent) and occurred between 3.5-5.5 hours. The pulse was noted to increase steadily after administering clozapine. 

Author Biography

Kane Christian Larson, University of British Columbia Faculty of Pharmacy
PharmD student (2019)


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