Clozapine is used in combination with psychotropic medication and a wide variety of non-psychotropic medications. This article reviews the literature on clozapine drug interactions and the effect these have on serum level changes in clozapine. A total of 54 articles with a total of 109 individual case reports were obtained by manual and computerised literature search from January 1970 to May 2013. Psychotropic medications most likely to increase clozapine levels include: fluvoxamine, lamotrigine, aripiprazole and the discontinuation of levomepromazine and carbamazepine. Non-psychotropic medications associated with increase in clozapine levels include: erythromycin, ciprofloxacin, omeprazole, cimetidine, OCP containing ethinylestradiol, amiodarone, aluminum hydroxide and isoniazid. Rifampin and St John's wort resulted in low clozapine levels. Smoking cessation also increased clozapine levels. The role of routine clozapine monitoring in clinical practice requires further clarification. In the absence of recommendations for routine clozapine level monitoring, clinical judgment should always be used in addition to diagnostic testing. Clinicians must maintain increased clinical vigilance for adverse side effects when clozapine is combined with other medications.

Benzodiazepines are mainstay medicines in rapid tranquillisation. Midazolam is a short acting benzodiazepine. It is not available for oral administration as this route of administration leads to poor bioavailability. It has recently become available in a new formulation specifically designed for buccal administration, and is also available as a solution for injection.

The absorption of intramuscular midazolam is erratic and it has an unpredictable propensity for causing profound oversedation. Healthcare providers who include IM midazolam in their rapid tranquillisation guidelines or policies need to ensure that clinicians using it have the necessary knowledge, skills and competencies surrounding its use including clinical sequelae and the use of the ‘antidote’ flumazenil.

This brief review describes midazolam's potential role in rapid tranquillisation via these routes, and discusses the risks and benefits of these options in order to help readers consider their places in regular clinical practice, particularly in light of the shortage of lorazepam injection.