title: Ciprofloxacin strongly inhibits clozapine metabolism: two case reports.
abstract: We report on two cases of drug-drug interactions between ciprofloxacin and clozapine. The first case was a 46-year-old male patient receiving a daily dose of clozapine 900 mg. He was admitted to hospital with urosepsis and was treated with a 5-day course of ciprofloxacin and amoxicillin. Two days after completion of antibacterial therapy, the patient developed symptoms of rhabdomyolysis. Clozapine therapy was discontinued and measurement of the patient's clozapine plasma concentration 1 day after cessation of clozapine therapy and 3 days after cessation of ciprofloxacin treatment showed that it was in excess of recommended therapeutic levels. The second patient was a 58-year-old male patient treated with a daily dose of clozapine 300 mg. He was admitted to hospital because of delirium and suspected urinary tract infection or pneumonia. Treatment with ciprofloxacin was initiated. Measurement of clozapine plasma concentrations prior to and 3 days after commencement of ciprofloxacin showed that clozapine concentrations doubled over that time period. We suggest that inhibition of cytochrome P450 (CYP) enzymes 1A2 and 3A4 by ciprofloxacin resulted in delayed clozapine metabolism and elevated clozapine plasma concentrations. This might cause severe adverse effects. We advise using another antibacterial agent or reducing the clozapine dose and monitoring clozapine levels when this antipsychotic agent is used in combination with ciprofloxacin.
authors.affiliation: Department of Pharmacy and Pharmacology, Slotervaart Hospital, the Netherlands Cancer Institute, Amsterdam, the Netherlands. Elke.Brouwers@slz.nl
authors.forename: E E M
authors.initials: EE
authors.lastname: Brouwers
authors.forename: M
authors.initials: M
authors.lastname: Söhne
authors.forename: S
authors.initials: S
authors.lastname: Kuipers
authors.forename: E C M
authors.initials: EC
authors.lastname: van Gorp
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: C H W
authors.initials: CH
authors.lastname: Koks
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: A D R
authors.initials: AD
authors.lastname: Huitema
mesh_terms: D000892:Anti-Infective Agents, Urinary / Q000378:metabolism* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000378:metabolism* / Q000627:therapeutic use; D003024:Clozapine / Q000378:metabolism* / Q000627:therapeutic use; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000188:drug therapy; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D000892:Anti-Infective Agents, Urinary; D014150:Antipsychotic Agents; D002939:Ciprofloxacin; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D003024:Clozapine