Clarithromycin × Theophylline

Clarithromycin slows the clearance of theophylline by liver enzymes, so theophylline blood levels rise (theophylline SmPC). The US Food and Drug Administration (FDA) gives an average increase of 25% (theophylline FDA label), and the clarithromycin SmPC calls the increase modest but statistically significant (clarithromycin SmPC). Theophylline has a narrow therapeutic range: above 20 mcg/mL, adverse reactions become more frequent and more severe (theophylline FDA label).

Nausea, tachycardia, tremor, insomnia, agitation. At levels above 30 mg/L: seizures and ventricular arrhythmias.

The combination can be used with monitoring. The theophylline SmPC lists clarithromycin among drugs that raise the risk of theophylline overdose and requires these patients to be monitored (theophylline SmPC). The US Food and Drug Administration (FDA) advises measuring the serum theophylline concentration when clarithromycin is added or stopped (theophylline FDA label), especially with high theophylline doses or a baseline level near the upper end of the therapeutic range (clarithromycin FDA label). The therapeutic range is 10–20 mcg/mL (theophylline SmPC). Lower the theophylline dose if needed (clarithromycin SmPC). Ask the patient to report nausea, vomiting, persistent headache, insomnia or a fast heartbeat (theophylline FDA label). If the theophylline dose was lowered, restore it after clarithromycin is stopped, otherwise theophylline levels will fall (theophylline FDA label).