Clozapine monitoring therapy

If WBC count is 2,000-3,000/mm or ANC is 1,000-1,500/mm, interrupt therapy and monitor for signs of infection. Perform WBC and differential counts daily. If there are no symptoms of infection, if WBC count returns to greater than 3,000/mm, and if ANC is greater than 1,500/mm, resume clozapine therapy with twice-weekly WBC and differential counts until total WBC count returns to more than 3,500/mm and ANC is greater than 2,000/mm. ... 

In this context, the first role of the laboratory is to detect specific adverse effects to target organs (see Role of the Laboratory later in this chapter). Monitoring will generally be tailored to the specific therapy used because of its known potential for causing certain problems. Examples include periodic blood counts with carbamazepine or clozapine and thyroid and renal function studies with long-term maintenance lithium. 

Freeman DJ, Oyewumi LK. Will routine therapeutic drug monitoring have a place in clozapine therapy Clin Pharmacokinei 1997 32 93-100. 

Combined therapy with clozapine and fluvoxamine (n = 11) and clozapine monotherapy (n = 12) have been monitored before and during the first 6 weeks of medication (39). The co-administration of fluvoxamine attenuated and delayed the clozapine-induced increase in plasma concentrations of tumor necrosis factor-alpha, enhanced and accelerated the clozapine-induced increase in leptin plasma concentrations without a significant effect on clozapine-induced weight gain, and reduced granulocyte counts. 

The latter is said to be the first reported case of pericarditis due to clozapine demonstrating rises in troponin I, which resolved despite continuation of therapy. The authors suggested that troponin I is the preferred marker for monitoring the cardiac adverse effects of clozapine. 

In a cohort study, based on a prospective drug exposure database, the effectiveness of centralized routine monitoring of blood counts was evaluated in 1500 patients taking clozapine between March 2001 and December 2001 (157). Seven patients developed severe neutropenia while taking clozapine (neutrophil counts below 1.5 x 109/ 1). The mean time to withdrawal of therapy was 1.6 days (maximum 6 days), and neutrophil counts recovered to normal in all cases after 6.4 days (maximum 13 days). Based on an estimate of 500 patient-years of exposure, the frequency of severe neutropenia was one case per 71 patient-years of therapy or 1.4% per annum. 

Psychotic patients are most often treated with clozapine, haloperidol, lithium, olanzapine, or one of the phenothi-azines, or a combination of these drugs. Because response to these drugs is unpredictable and patients are difficult to control, monitoring serum concentration may aid in adjusting therapy. Numerous methods to measure the serum concentration of the various neuroleptic agents have been reported. ... 

Cohen D, Bogers JP, van Dijk D, Bakker B, Schvdte PF. Beyond white blood cell monitoring screening in the initial phase of clozapine therapy. J Clin Psychiatry 2012 73(10) 1307-12. 

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