Ciprofloxacin and Clozapine: A Potentially Fatal butUnderappreciated Interaction

Clozapine provides a 50%–60% response rate in refractory schizophrenia but has a narrow therapeutic index and issusceptible to pharmacokinetic interactions, particularly with strong inhibitors or inducers of cytochrome P450 (CYP) 1A2.CaseReport.We report the case of a 28-year-old nonsmoking female with intellectual disability who was maintained for 3 years onclozapine 100 mg orally twice daily. The patient was treated for presumptive urinary tract infection with ciprofloxacin 500 mg orallytwice daily and two days later collapsed and died despite resuscitation efforts. The postmortem femoral clozapine plasma level wasdramatically elevated at 2900 ng/mL, and the cause of death was listed as acute clozapine toxicity.Conclusion.Given the potentiallyfatal pharmacokinetic interaction between clozapine and ciprofloxacin, clinicians are advised to monitor baseline clozapine levelsprior to adding strong CYP450 1A2 inhibitors, reduce the clozapine dose by at least two-thirds if adding a 1A2 inhibitor such asciprofloxacin, check subsequent steady state clozapine levels, and adjust the clozapine dose to maintain levels close to those obtainedat baseline.