Minor symptoms are not predictive of elevated theophylline levels in adults on chronic therapy

Theophylline toxicity is associated with significant morbidity and mortality. While a relationship of the serum theophylline level to symptoms associated with toxicity has been described in acutely intoxicated or elderly patients, this relationship may not be valid in younger patients receiving chronic theophylline therapy.

This study was designed to define the predictive value and prevalence of minor symptoms of theophylline toxicity in ambulatory asthmatic adults receiving chronic theophylline therapy with elevated serum theophylline levels.

We conducted a retrospective study to determine the prevalence of symptoms in patients with elevated theophylline levels ( > 20 mg/L or 110 mumol/L). A prospective study was performed to ascertain the sensitivity, specificity, and predictive value of symptoms as an indication of elevated the theophylline level. In addition, we describe a patient who had a seizure in association with an elevated theophylline level in the absence of any preceding symptom of theophylline toxicity.

We reviewed the result of 483 theophylline measurements in 450 asthmatic patients. In 46 instances the theophylline levels was > 20 mg/L. Only three of these patients were symptomatic. Ninety patients were prospectively studies with a total of 111 theophylline measurements of which 13 exceeded 20 mg/L. None of the symptoms (ie, nausea or gastrointestinal upset; headache or palpitations, irregular heart beat, tremor, or shakiness) was a sensitive predictor of an elevated theophylline level.

Elevation of the theophylline level is frequently associated with lack of symptoms in young ambulatory asthmatic adults receiving chronic theophylline therapy. The question of whether cardiac or neurologic electrophysiologic abnormalities might exist in the absence of symptoms is an issue that needs to be addressed. Clinicians should continue to monitor serum levels on a regular basis and prescribe this drug conservatively.