Theophylline

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Introduction

Theophylline is the cornerstone in the management of both the acute and chronic phases of reversible airway obstruction. However, it has a narrow therapeutic index. Fortunately, theophylline serum levels correlate well with both therapeutic and toxic effects. Concentrations of 10-20 mg/l are needed to produce bronchodilation with a minimum of side effects. Serum levels exceeding 20 mg/l are associated with an unacceptable incidence of adverse reactions. Theophylline levels above 35 mg/l increase the incidence of seizures and cardiac arrhythmias.

The clearance of theophylline is affected by many variables which necessitate carefully individualized dosage. Age, smoking, congestive heart failure, other diseases and drug interactions all contribute to a change in the metabolism of theophylline. These factors all necessitate dosage adjustments in order to achieve and maintain therapeutic serum levels and avoid toxicity.

So wide is the variation in clearance rates that no dose which will produce effective levels of theophylline in most patients will fail to produce toxic levels in a few. Serum theophylline measurements are essential for accurate dosage adjustment.

There have been clinical reports suggesting dose dependent elimination of theophylline in some patients, especially at the higher end of the therapeutic range and most obviously at concentrations greater than 20 mg/l. For these patients, small increases in doses may result in dramatic increases in serum concentrations. Such patients have not been well characterized. Therefore, to minimize the risk of toxicity, doses of theophylline should be increased cautiously, especially at the upper levels of the therapeutic range.