Version January 2024
| Drug | Type of interaction | Effect on theophylline serum concentrations or pharmacologic effect |
| Adenosine | Theophylline blocks adenosine receptors | Higher doses of adenosine may be required to achieve desired anti-arrhythmic effect |
| Alcohol | A single large dose of alcohol (3 ml/kg of whiskey) decreases theophylline clearance for up to 24 hours | 33 percent increase |
| Allopurinol | Decreases theophylline clearance at allopurinol doses ≥600 mg/day | 25 percent increase |
| Aminoglutethimide | Increases theophylline clearance by induction of microsomal enzyme activity | 25 percent decrease |
| Carbamazepine | Similar to aminoglutethimide | 30 percent decrease |
| Cimetidine | Decreases theophylline clearance by inhibiting cytochrome P450 1A2 | 70 percent increase |
| Ciprofloxacin | Similar to cimetidine | 40 percent increase |
| Clarithromycin | Similar to erythromycin | 25 percent increase |
| Diazepam | Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors | Larger diazepam doses may be required to produce desired level of sedation |
| Discontinuation of theophylline without reduction of diazepam dose may result in respiratory depression | ||
| Disulfiram | Decreases theophylline clearance by inhibiting hydroxylation and demethylation | 50 percent increase |
| Enoxacin | Similar to cimetidine | 300 percent increase |
| Ephedrine | Synergistic CNS effects | Increased frequency of nausea, nervousness, and insomnia |
| Erythromycin | Erythromycin metabolite decreases theophylline clearance by inhibiting cytochrome P450 3A3 | 35 percent increase. Erythromycin steady-state serum concentrations decrease by a similar amount |
| Estrogen | Estrogen-containing oral contraceptives decrease theophylline clearance in a dose-dependent fashion. The effect of progesterone on theophylline clearance is unknown | 30 percent increase |
| Flurazepam | Similar to diazepam | Similar to diazepam |
| Fluvoxamine | Similar to cimetidine | Similar to cimetidine |
| Halothane | Halothane sensitizes the myocardium to catecholamines; theophylline increases release of endogenous catecholamines | Increased risk of ventricular arrhythmias |
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