CLOZAPINE DRUG-DRUG INTERACTIONS - A REVIEW OF THE LITERATURE

Clozapine is often used in combination with other medications. To date , there has been no comprehensive review of drug-drug interactions inv olving clozapine. This review summarizes published reports of suspecte d drug-drug interactions, and assesses their clinical significance. A computerized search was conducted using MEDLINE (1975-1996) to retriev e 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 pharmacoki netic and pharmacodynamic interactions when prescribed concurrently wi th most major classes of therapeutic agents. In general, the addition of other medications with similar pharmacological effects or side-effe cts to clozapine may enhance these effects in an additive or possibly synergistic manner. The selective serotonin reuptake inhibitor fluvoxa mine was involved in the most thoroughly documented pharmacokinetic in teractions, while a number of reports were found implicating various b enzodiazepines 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 concu rrently with clozapine.