Intranasal Theophylline: A Novel Method to Treat Patients with Smell Loss (Hyposmia)

Abstract

While the oral phosphodiesterase (PDE) inhibitor theophylline has proven useful in the treatment of hyposmia its efficacy has been limited by its side effects, its slow action to improve olfactory function requiring months of drug use and by development of drug resistance. To overcome these adverse effects an open label, single source clinical trial using intranasal theophylline was performed in 10 patients with hyposmia before and after both oral and intranasal theophylline. Intranasal theophylline was administered daily in each naris at a dose of 20μg of buffered drug through use of a clinically adapted syringe which delivered the drug into the mid‐upper nose. Patients were studied weekly for two weeks and then biweekly for four weeks. Both subjective and objective measurements of smell and taste function were obtained. After one week of intranasal drug eight of the 10 patients reported subjective improvement in both taste and smell function and appetite. Objective measurements with smell and taste function tests also improved in each of these patients. This improvement continued over the subsequent three weeks of the study. No side effects were experienced by any patient. Blood theophylline levels at the time of maximal smell and taste improvement were 0. After one week of discontinuing the intranasal drug two patients reported subjective diminution in smell function confirmed by objective smell and taste measurements whereas six patients maintained improvement for two months after intranasal theophylline was discontinued. This open label clinical trial suggests that intranasal theophylline is both safe and more effective than oral theophylline in the treatment of hyposmia.