A 58-year-old COPD patient stabilised on oral theophylline is started on ciprofloxacin for a urinary infection. Three days later she develops nausea, sinus tachycardia of 140 per minute and a generalised seizure. The most likely mechanism is:

• A Additive QT prolongation leading to torsades de pointes
• B Ciprofloxacin-mediated inhibition of theophylline metabolism, causing theophylline toxicity ✓
• C Displacement of theophylline from plasma proteins by ciprofloxacin
• D Synergistic GABA antagonism at the seizure focus

Explanation

Theophylline is cleared mainly by hepatic cytochrome P450 oxidation (CYP1A2). Fluoroquinolones such as ciprofloxacin and macrolides such as clarithromycin inhibit this metabolism, raising theophylline levels above the toxic threshold of about 20 microgram/mL. Seizures and life-threatening arrhythmias are the classic severe manifestations of theophylline toxicity. Protein binding of theophylline is minimal, so displacement is not a plausible mechanism here.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

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