Should not be administered more often than every 4 hours or within 12 hours following oral, parenteral or rectal use of other xanthine containing preparations. Simultaneous use of additional xanthines by any route should be avoided in all patients, especially children. Synergism with ephedrine has been documented and may occur with other sympathomimetic amines. Theophylline may cause increased excretion of lithium carbonate. Theophylline antagonizes the effect of propranolol.
Theophylline potentiates the effects of diuretics and the cardiac effect of digitalis glycosides.
The concomitant use of morphine, stilbamidine, curare may antagonize the effect of theophylline since these drugs stimulate histamine release and thereby induce bronchoconstriction. Cigarette smoking and phenobarbital shorten, while alcohol consumption increases the half-life of theophylline. Xanthines have been shown to be nephrotoxic with prolonged use at high dosage. Coincident toxicity should therefore be borne in mind when other potentially nephrotoxic drugs are administered concurrently. Acidifying agents, by increasing urinary excretion of weak bases like the xanthines, inhibit theophylline action.