A 62-year-old man with COPD stabilized on theophylline is started on ciprofloxacin for infective exacerbation. Three days later he develops tremors, tachycardia, and a generalized seizure. Serum theophylline level is markedly elevated. The interaction responsible is:

• A Ciprofloxacin displaces theophylline from plasma proteins, raising free levels
• B Ciprofloxacin reduces renal clearance of theophylline through competition at organic anion transporters
• C Ciprofloxacin inhibits CYP1A2, decreasing hepatic theophylline metabolism ✓
• D Ciprofloxacin induces CYP3A4, converting theophylline to a toxic metabolite

Explanation

Ciprofloxacin is one of the strongest inhibitors of CYP1A2, the principal enzyme clearing theophylline. Co-administration raises theophylline levels substantially and produces toxicity manifesting as tremor, arrhythmia, and seizures. Enoxacin is even more potent in this interaction while moxifloxacin has negligible CYP1A2 inhibition. Protein-binding displacement is clinically insignificant for theophylline, which has a low extraction ratio cleared almost entirely by hepatic metabolism, not renal excretion. Fluoroquinolones are CYP inhibitors, not inducers.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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