title: Ciprofloxacin and Clozapine: A Potentially Fatal but Underappreciated Interaction.
abstract: Objective.Clozapine provides a 50%-60% response rate in refractory schizophrenia but has a narrow therapeutic index and is susceptible to pharmacokinetic interactions, particularly with strong inhibitors or inducers of cytochrome P450 (CYP) 1A2.Case Report.We report the case of a 28-year-old nonsmoking female with intellectual disability who was maintained for 3 years on clozapine 100 mg orally twice daily. The patient was treated for presumptive urinary tract infection with ciprofloxacin 500 mg orally twice daily and two days later collapsed and died despite resuscitation efforts. The postmortem femoral clozapine plasma level was dramatically elevated at 2900 ng/mL, and the cause of death was listed as acute clozapine toxicity.Conclusion.Given the potentially fatal pharmacokinetic interaction between clozapine and ciprofloxacin, clinicians are advised to monitor baseline clozapine levels prior to adding strong CYP450 1A2 inhibitors, reduce the clozapine dose by at least two-thirds if adding a 1A2 inhibitor such as ciprofloxacin, check subsequent steady state clozapine levels, and adjust the clozapine dose to maintain levels close to those obtained at baseline.
authors.affiliation: Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, MC 0603, La Jolla, CA 92093-0603, USA; California Department of State Hospitals (DSH), Psychopharmacology Resource Network, 3102 East Highland Avenue, Patton, CA 92369, USA.
authors.forename: Jonathan M
authors.identifier: 0000-0001-7294-4834
authors.initials: JM
authors.lastname: Meyer
authors.affiliation: California Department of State Hospitals (DSH), Psychopharmacology Resource Network, 3102 East Highland Avenue, Patton, CA 92369, USA.
authors.forename: George
authors.initials: G
authors.lastname: Proctor
authors.affiliation: California Department of State Hospitals (DSH), Psychopharmacology Resource Network, 3102 East Highland Avenue, Patton, CA 92369, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cummings
authors.affiliation: California Department of State Hospitals (DSH), Clinical Operations Advisory Council, Bateson Building, 1600 9th Street, Room 400, Sacramento, CA 95814, USA.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Dardashti
authors.affiliation: Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, MC 0603, La Jolla, CA 92093-0603, USA; California Department of State Hospitals (DSH), Director of Psychopharmacology Services, Bateson Building, 1600 9th Street, Room 400, Sacramento, CA 95814, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Stahl