Ciprofloxacin × Theophylline

Ciprofloxacin inhibits hepatic CYP1A2, the enzyme that clears theophylline, so theophylline levels rise. The FDA theophylline label puts the increase at about 40%. Theophylline has a narrow margin: per the same label, above 20 mcg/mL both the frequency and severity of adverse reactions increase. The FDA ciprofloxacin label reports serious and fatal reactions with this combination, including cardiac arrest, seizures, status epilepticus and respiratory failure.

Tachycardia, tremor, nausea, vomiting, seizures, arrhythmias when theophylline above 20 mcg/mL.

The combination is avoided, as the FDA ciprofloxacin label states, though no label lists it as a contraindication. A patient on theophylline gets an antibiotic without this interaction, for example amoxicillin-clavulanate for pneumonia. Levofloxacin does not change theophylline levels according to its SmPC, but together with theophylline it markedly lowers the seizure threshold. If ciprofloxacin is still needed, the theophylline SmPC caps the theophylline dose at no more than 60% of the recommended dose. Serum theophylline is measured during the course and after ciprofloxacin stops, and the dose follows the result. Nausea, vomiting, tremor or palpitations call for a same-day level.