REASSESSING THE THERAPEUTIC RANGE FOR THEOPHYLLINE ON LABORATORY REPORT FORMS: ANOTHER PERSPECTIVE

Abstract

The therapeutic utility of theophylline and the recommended range for serum concentrations are debated in a series of three editorials by noted contributors in this area. In the first, it is pointed out that the role of theophylline has evolved into an "adjunctive" therapy for asthma and chronic obstructive pulmonary disease. Serum concentrations of 10 to 15 µg/mL do not sacrifice significant clinical benefit, whereas there is increased risk for adverse effects at higher concentrations. Changing laboratry report forms to designate a lower therapeutic range of 5 to 15 µg/mL for an increased margin of safety (with >20 µg/mL continuing as the lower limit of the toxic range) is advocated and a stepwise approach for implementing this change is proposed. The second paper supports the view that theophylline remains more important than a third- or fourth-line agent in the treatment of asthma, particularly in selected patients. A higher target serum concentration range of 10 to 15 µg/mL may be desirable in more severe asthmatics (requiring oral steroids despite treatment with inhaled steroid), those with nocturnal symptoms, acute exacerbations requiring hospitalization and mechanical ventilation, and in patients for whom this is a more economical or preferable therapy. In these patients a serum concentration of 5 µg/mL may be too low to achieve sufficient benefit. Designation of "10 to 15 µg/mL (5 to 20)" as the therapeutic range is suggested to emphasize the midrange as the target while indicating that levels between 5 and 20 µg/mL are acceptable, although not ideal from either an efficacy or safety standpoint. In the third and final viewpoint presented, much data supporting the efficacy of theophylline in the treatment of chronic asthma and its relationship to serum concentrations are presented. Evidence for potential anti-inflammatory effects of theophylline is also reviewed. Severe toxicity, a rare event, is noted to be not a result of serum concentrations slightly above the therapeutic range, but from massive overdosage and/or drug interactions or concomitant illnesses that alter elimination of the drug. No changes in the recommended therapeutic range of theopylline, which might alter its effectiveness, are proposed. Rather, more careful use and monitoring through education of prescribers is advocated.