Major
Clarithromycin × Theophylline
Macrolide antibiotic×Methylxanthine
Mechanism
Clarithromycin blocks CYP1A2 and CYP3A4 – theophylline metabolic routes. Theophylline plasma levels rise 2- to 3-fold. Theophylline has a narrow therapeutic window.
Symptoms
Nausea, tachycardia, tremor, insomnia, agitation. At levels above 30 mg/L: seizures and ventricular arrhythmias.
Management
Avoid the combination. Alternative antibiotics without CYP1A2/CYP3A4 inhibition: a cephalosporin, amoxicillin-clavulanate, or doxycycline. If clarithromycin is needed, halve theophylline and check level at 3 days.