Possible Adverse Interaction between Clozapine and Ampicillin in an Adolescent with Schizophrenia

A 17 year old with probable schizophrenia, who showed a therapeutic response to clozapine (12.5 mg t.i.d.), was treated for sinusitis with a routine dose of ampicillin (a semisynthetic penicillin). Within a day, the patient became sleepy, appeared distractible, performed routine activities slowly, and exhibited hypersalivation. There was no evidence of delirium, other neurotoxic or autonomic signs, or metabolic dysregulation. These changes disappeared promptly on replacement of ampicillin with a chemically unrelated antibiotic. Especially in view of the hypersalivation, a characteristic side effect of clozapine, it was hypothesized that there may be a drug interaction between clozapine and ampicillin. This hypothesis was further explored by use of differential absorption spectrophotometry to investigate the possibility of a molecular interaction between these two agents in vitro. Spectrophotometric findings suggest that clozapine interacts in vitro with ampillicin, as well as with penicillin G; a different type of drug interaction was observed with tetracycline, but there was no apparent interaction with streptomycin. Although the hypothesized drug interaction has not been fully demonstrated in a clinical setting, physicians may wish to be aware of the theoretical possibility of drug interactions between clozapine and certain antibiotics.