title: Ciprofloxacin-induced theophylline toxicity: a population-based study.
abstract: OBJECTIVE
  Ciprofloxacin can inhibit the cytochrome P450-mediated metabolism of theophylline, but the clinical relevance of this drug interaction is uncertain. We studied the risk of theophylline toxicity associated with the co-prescription of ciprofloxacin and theophylline.
  
  
  METHODS
  This was a population-based, nested case-control study of a cohort of Ontario residents aged 66 years of age or older treated with theophylline between April 1, 1992 and March 31, 2009. Within this group, case patients were those hospitalized with theophylline toxicity. For each case, 50 age- and sex-matched control patients were identified from the same cohort. The odds ratio (OR) for the association between hospitalization for theophylline toxicity and receipt of ciprofloxacin in the 14 days preceding hospitalization was determined.
  
  
  RESULTS
  Among the 77,251 elderly patients receiving therapy with theophylline, 180 eligible case patients hospitalized for theophylline toxicity and 9000 matched controls were identified. Following multivariable adjustment, a nearly twofold increase in the risk of theophylline toxicity following the receipt of ciprofloxacin was observed [adjusted OR 1.86, 95% confidence interval (CI) 1.18-2.93]. In contrast, there was no increased risk of theophylline toxicity within a group of patients receiving neutral comparator antibiotics (levofloxacin, trimethoprim-sulfamethoxazole or cefuroxime) (adjusted OR 0.78; 95% CI 0.38-1.62).
  
  
  CONCLUSIONS
  Treatment with ciprofloxacin is associated with a significant increase in the risk of theophylline toxicity. When clinically appropriate, alternate antibiotics should be considered for elderly patients receiving theophylline.
authors.affiliation: University of Toronto, Toronto, ON, Canada. tantoniou@smh.toronto.on.ca
authors.forename: Tony
authors.initials: T
authors.lastname: Antoniou
authors.forename: Tara
authors.initials: T
authors.lastname: Gomes
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Mamdani
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D009864:Ontario; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism; D013806:Theophylline / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D002939:Ciprofloxacin; D013806:Theophylline