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Clinically significant drug interactions with theophylline

Clinically significant drug interactions with theophylline
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
Drugs_interact_theophylline.htm
Redrawn from Hendeles, L, Jenkins, J, Temple, R, Pharmacotherapy 1995; 15:409.
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