Theophylline. A "state of the art" review

Theophylline is a bronchodilator and respiratory stimulant that is effective in the treatment of acute and chronic asthma, Cheyne-Stokes respirations, and apnea/bradycardia episodes in newborns. It is also used as an adjunct in the treatment of congestive heart failure and acute pulmonary edema, but it has no established efficacy in patients with chronic irreversible airways obstruction. Benefits and risks from theophylline relate directly to serum concentration, which is a function of both dose and elimination characteristics of the drug in an individual patient. When used to treat acute symptoms, an initial loading dose based on a mean volume of distribution is required to rapidly obtain maximum bronchodilator effect. Because of large interpatient differences in elimination, constant intravenous infusion rates for continued therapy must be guided by monitoring serum theophylline concentration at intervals until a steady-state serum concentration is reached within the 10-20 micrograms/ml therapeutic range. Intravenous, oral or rectal solutions and plain uncoated tablets are appropriate for acute therapy, while reliably absorbed slow-release formulations offer therapeutic advantages for the management of chronic asthma, particularly in patients with rapid elimination. Dosage for long-term therapy is determined by starting with low doses that allow virtually complete acceptance of the medication followed by gradual increases, if tolerated, at three day intervals until mean age-specific doses are reached. Subsequent adjustment in dosage regimens are then based upon serum concentration measurements. Most clinical laboratories now measure theophylline, and newer systems have been developed to provide emergency results within minutes at a reasonable cost. In cases of theophylline poisoning, the drug must be rapidly removed to prevent life-threatening toxicity. When serum concentrations are in excess of 60 micrograms/ml charcoal hemoperfusion dialysis may be indicated, even in the absence of obvious signs of toxicity.