Case report: 72-year-old male with multi-infarct dementia and diabetes mellitus, on low dose clozapine for behavioral management (18.75 mg/d). Ciprofloxacin 500 mg BID started for leg ulcer. Ten days later the patient developed agitation, requiring hospitalization. At time of admission the clozapine level was 90 ng/mL. After ciprofloxacin was discontinued, clozapine levels dropped below the limit of detection (50 ng/mL).
Randomized, double-blind, cross-over study in 7 schizophrenia inpatients who volunteered to receive either 250 mg BID ciprofloxacin or placebo BID for 7 days. Ciprofloxacin increased mean serum concentration of clozapine and DMC by 29% () and 31% (), respectively. There was a significant positive correlation (, ) between the ciprofloxacin level and increase in total concentration of clozapine + DMC.
Case report: 46-year-old male with schizophrenia on clozapine 400 mg/d with adherence issues, but whose highest plasma levels in the prior 6 months for clozapine and DMC were 500 ng/mL and 375 ng/mL, respectively. Levels obtained on a clozapine dose of 500 mg/d before ciprofloxacin was introduced were clozapine 354 ng/mL; DMC 194 ng/mL. The ratio of clozapine to DMC was 1.82. The clozapine dose was increased to 775 mg/d (a 1.6-fold change), and later ciprofloxacin 1500 mg/d was started for a UTI. The clozapine and DMC levels increased to 1218 ng/mL and 371 ng/mL, respectively, a 3.4-fold change for clozapine. The clozapine/DMC ratio increased to 3.33. Repeat clozapine and DMC levels after 3 days on ciprofloxacin 3000 mg/day and clozapine 775 mg/day were 1197 ng/mL and 475 ng/mL, respectively. Nine days after discontinuing ciprofloxacin, clozapine and DMC levels decreased 39% and 54%, respectively, to 730 ng/mL and 256 ng/mL after only a 19% drop in the clozapine dose to 600 mg/day.
Case report: 47-year-old male, chronic inpatient with schizophrenia, managed on clozapine 750 mg/d along with amisulpride 450 mg/d and lorazepam 4.5 mg/d. Patient developed acute epididymo-orchitis for which ciprofloxacin was recommended, but at the lower dose of 500 mg BID instead of 750 mg BID to minimize kinetic interactions with clozapine. The serum clozapine level on the day before ciprofloxacin was started was 550 ng/mL but rose to 2570 ng/mL after 4 days of treatment with ciprofloxacin. The clozapine dose was reduced 40% to 450 mg/d, and the repeat level on day 14 of ciprofloxacin treatment was 130 ng/mL. There was no change in smoking status.
Case report: 64-year-old female with schizophrenia on long-term clozapine therapy was admitted to a hospital for treatment of urosepsis. When the admission EKG showed prolonged QTc and an echocardiogram revealed hypokinesia, clozapine was stopped. When clozapine was resumed one month later after other antipsychotics failed, the patient exhibited no issues with intolerance. However, 4 months later she was readmitted with mental status changes after starting on ciprofloxacin for another UTI. The clozapine level was elevated at 1498 ng/mL.
Case reports: Case One: 46-year-old male with schizophrenia on clozapine 900 mg/d was admitted to a hospital for treatment of urosepsis. He received intravenous ciprofloxacin 400 mg BID for 4 days and was discharged without adverse effects, but the patient did lose 7 kg during the stay. Three days later, he was admitted with rhabdomyolysis. Labs revealed a CK of 195,000 U/L and abnormal liver function tests. The clozapine level obtained 24 hours after stopping clozapine was 890 ng/mL, but no levels were obtained during ciprofloxacin treatment. The authors deemed the interaction with ciprofloxacin probable. Case Two: 58-year-old male with schizophrenia on clozapine 300 mg/d was admitted to a hospital for treatment of urosepsis. He received 2 days of intravenous ciprofloxacin 200 mg BID for 4 days before ciprofloxacin was stopped due to concerns about the interaction with clozapine. Clozapine plasma levels measured prior to and 3 days after the start of ciprofloxacin were 850 ng/mL and 1720 ng/mL, respectively. The authors deemed the interaction with ciprofloxacin probable.
