Abstract: | Clozapine is often used in combination with other medications. To date, there has been no comprehensive review of drug–drug interactions involving clozapine. This review summarizes published reports of suspected drug–drug interactions, and assesses their clinical significance. A computerized search was conducted using MEDLINE (1975–1996) to retrieve all reports of adverse events associated with the concurrent use of clozapine and other agents. Forty-three reports involving 19 different drugs were evaluated. Clozapine appeared to be involved in pharmacokinetic and pharmacodynamic interactions when prescribed concurrently with most major classes of therapeutic agents. In general, the addition of other medications with similar pharmacological effects or side-effects to clozapine may enhance these effects in an additive or possibly synergistic manner. The selective serotonin reuptake inhibitor fluvoxamine was involved in the most thoroughly documented pharmacokinetic interactions, while a number of reports were found implicating various benzodiazepines in apparent pharmacodynamic interactions. No clozapine–drug combination is absolutely contraindicated, but some members of a given therapeutic class may pose less risk than others when used concurrently with clozapine. © 1997 John Wiley & Sons, Ltd. |