Alternative Routes of Administration of Clozapine

Plasma Clozapine and Norclozapine After Use of Either Crushed Tablets or Suspension Compared With Tablets

“…Orodispersible tablets are also manufactured, and a range of other formulations is either available or under investigation for clinical use. 7,22 Clozapine is not water soluble, and thus, a liquid formulation for oral use must be a suspension, which brings with it the problems of ensuring the homogeneity of the product before it is given to patients and of quantitatively transferring the suspension to the patient. This concern was highlighted in our laboratory many years ago when residues of clozapine suspension in bottles that had been used in patient treatment were analyzed and found to contain clozapine at concentrations many, many times that intended.…”

“…The use of crushed clozapine tablets suspended in water, in pediatric base, 6 or dispersed in some other medium has proved useful when attempting either to improve adherence or to suit patient preference for many years. Orodispersible tablets are also manufactured, and a range of other formulations is either available or under investigation for clinical use 7,22 . Clozapine is not water soluble, and thus, a liquid formulation for oral use must be a suspension, which brings with it the problems of ensuring the homogeneity of the product before it is given to patients and of quantitatively transferring the suspension to the patient.…”

Letter to the Editors in Response to: Flanagan RJ, Hunter S, Obee S, Reeves S. Plasma Clozapine and Norclozapine After Use of Either Crushed Tablets or Suspension Compared With Tablets

“…To the Editor: W e thank Professor Taylor for his interest in our article 1 and for his helpful comments. 2 We feel that we all agree that clozapine administration as crushed tablets suspended in an appropriate medium or as a proprietary suspension or liquid formulation is a valuable dosing strategy in appropriate circumstances. In addition, it seems that giving clozapine in this way would give rise, on average, to lower predose plasma clozapine and norclozapine concentrations than if the same dose were prescribed as tablets.…”

“…In addition, it seems that giving clozapine in this way would give rise, on average, to lower predose plasma clozapine and norclozapine concentrations than if the same dose were prescribed as tablets. [1][2][3][4] Hence, it is important to consider the mode of administration when reporting clozapine dose-to-plasma concentration relationships, for example.…”

“…Other explanations present themselves. For example, the formulation of clozapine might affect the drug's absorption and bioavailability 2 . Alternatively, as the authors note, because patients who are prescribed liquid clozapine are usually those who are suspected of noncompliance with the tablet form, lower plasma levels might simply reflect a degree of noncompliance with liquid clozapine (eg, by missing doses due to refusal or by covertly spitting out unswallowed liquid).…”