theophylline and ciprofloxacin

Ciprofloxacin inhibits cytochrome P450 1A2 (CYP1A2), the primary enzyme responsible for the metabolism of theophylline. This inhibition reduces theophylline clearance, leading to increased plasma concentrations and a prolonged half-life, which can result in accumulation and toxicity.

Theophylline toxicity may occur, manifesting as nausea, vomiting, abdominal pain, diarrhoea, restlessness, tremor, tachycardia, cardiac arrhythmias, and in severe cases, seizures. The risk is increased in patients with pre-existing cardiac or seizure disorders, and the effect can be substantial, especially with higher doses of ciprofloxacin.

Avoid concurrent use if possible, as alternative antibiotics with minimal CYP1A2 inhibition (e.g., levofloxacin) may be considered. If co-prescription is necessary, reduce the theophylline dose by up to 50% and closely monitor serum theophylline concentrations and clinical signs of toxicity. Repeat theophylline levels should be measured after initiating or adjusting ciprofloxacin therapy, and further dose adjustments made as required.

This interaction is well-established and documented in clinical literature. Ciprofloxacin is a known inhibitor of CYP1A2, and numerous studies have demonstrated increases in theophylline concentrations and case reports of toxicity. The interaction is described in the Summaries of Product Characteristics for both drugs and in standard drug interaction databases. Practice varies in that some guidelines recommend avoiding the combination, while others permit it with appropriate dose reduction and monitoring.