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

Abstract

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 autonomie 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.Clozapine, an atypical NEUROLEPTic whose use in treating schizophrenia in adults is well established (Bunney 1992), is being increasingly used in adolescent psychiatry in Europe and the United States. Although publications about its possible side effects are becoming more frequent (Schmidt et al. 1990, Amminger et al. 1992, Birmayer et al. 1992, Remschmidt et al. 1994, this is the first report of a possible drug interaction between clozapine and the commonly used antibiotic ampillicin. CASE REPORTA 17-year-old boy was hospitalized following presentation with delusions and suicidal ideation. His father had schizophrenia, and both parents had mental retardation. Parents were unable to care for the child, and he was placed in a foster home at age 2 years. At age 4 years, he was evaluated for daytime

Clinically Relevant Interactions between Atypical Antipsychotics and Anti-Infective Agents

“…4.1.5. Ampicillin Csik and Molnar [60] proposed that a case of symptoms of clozapine intoxication during sinusitis was explained by ampicillin inhibition of clozapine metabolism. As ampicillin is not known to be a CYP inhibitor [5], the case was reinterpreted by proposing that the clozapine intoxication was explained by the cytokines released during the sinusitis [32].…”

The clinical use of plasma clozapine levels

“…Similarly stress, hypoalbuminaemia due to malnutrition or hepatic failure, and changes in drug-binding due to renal failure have the potential to increase plasma levels of clozapine. Other drug interactions have been reported, the mechanisms of which are as yet unclear [25,26].…”