Is Combined Therapy of Sympathomimetics and Theophylline Indicated?

Abstract

Bronchodilator effect and toxicity of theophylline 300 mg twice a day (R₁), salbutamol 4 mg tid (R₂), their combination in higher (200/4mg, R₃), and lower doses (100/2mg R₄), and placebo (calcium lactate 300 mg) tid (R₅) were compared in 25 patients with bronchial asthma in a randomized crossover trial. Statistically significant improvement in forced expiratory volume in one second (FEV₁) was observed in all the active treatment groups (R₁ to R₄) compared with placebo (R₅). The mean improvement in FEV₁ was 29.0%, 22.0%, 28.0%, 30.0%, and 0.73% in regimen R₁, R₂, R₃, R₄, and R₅, respectively day 1, and corresponding improvement was 30.0%, 24.0%, 29.0%, 34.0%, and 4.4% on completion of one week therapy. On intergroup statistical comparison, mean improvement in pulmonary function test values were statistically significant or highly significant in regimens R₁ to R₄, as compared with placebo. However, improvement between any two regimens was not statistically significant in any of the regimens (R₁-R₄). Almost all the regimens were tolerated well and no patient showed major adverse reactions or cardiotoxicity necessitating withdrawal of the drug. On the other hand, minor adverse reactions were common and the high dose combination (R₃) was found to have more adverse reactions than the low dose combination and either drug used alone.