A prospective clinical study of theophylline safety in 3810 elderly with asthma or COPD

Abstract

A large-scale prospective study was conducted in 3810 Japanese elderly (> or =65 years old) patients with asthma or chronic obstructive pulmonary disease (COPD) who had been treated with sustained-release theophylline tablets (THEODUR) at a dose of 400 mg/day for 1-6 months, in principle. Among 3798 protocol-complying patients (mean age: 73.8 +/- 0.10 years, 1997 with COPD), 261 theophylline-related adverse events were observed in 179 (4.71%) patients. The 5 most frequently observed adverse events were "nausea" (40 episodes, 1.05%), "loss of appetite" (22 episodes, 0.56%), "hyperuricemia" (16 episodes, 0.42%), "palpitation" (15 episodes, 0.39%), and "increased alkaline phosphatase" (11 episodes, 0.28%). No convulsions were reported. Six patients had serious adverse events. The incidence of theophylline-related adverse events was higher in patients with hepatic disease (odds ratio: 1:1.81) and in patients with arrhythmia (odds ratio: 1:1.88). Blood drug concentration measurements in 736 patients indicated that the drug levels were < or =15 microg/ml in 641 patients (87.1%), and no correlation was noted between dose and theophylline-related adverse events. These results suggest that sustained-release theophylline can be used safely in elderly patients with asthma or COPD.

EMPADE Study: Evaluation of Medical Prescriptions and Adverse Drug Events in COPD Patients Admitted to Intensive Care Unit

“…Out of the total drugs, just 2.43% lead to ADEs, which was extremely less compared to a study conducted by N Tyagi et al, wherein the number was 31.5% [5]. Gallelli and Buajordet with their teams found that bronchodilators were responsible for 18.5% and 19.5% of all ADEs [7], whereas theophylline was found to be responsible for maximum ADEs, these reports were similar to our results [7,23].…”

“…This observation was relatively similar to a previous study with ratio of ADEs in patients above 60 years to adults as 2.5 [7]. The five most frequently observed ADEs in our study were different from a past study [23]. Out of the total drugs, just 2.43% lead to ADEs, which was extremely less compared to a study conducted by N Tyagi et al, wherein the number was 31.5% [5].…”

Interactions between Theophylline and Salbutamol on Cytokine Release in Human Monocytes

“…Statistically significant effects were seen even below the generally accepted bronchodilatory plasma concentration range of the drug (55-110 M or 10 -20 mg/liter) (Barnes and Pauwels, 1994;Ohta et al, 2004). Recent reports have shown that low doses of theophylline, resulting in plasma concentrations lower than 50 M, have significant in vivo anti-inflammatory effects in treated asthmatics (Barnes and Pauwels, 1994;Oliver et al, 2001;Ohta et al, 2004).…”

“…Statistically significant effects were seen even below the generally accepted bronchodilatory plasma concentration range of the drug (55-110 M or 10 -20 mg/liter) (Barnes and Pauwels, 1994;Ohta et al, 2004). Recent reports have shown that low doses of theophylline, resulting in plasma concentrations lower than 50 M, have significant in vivo anti-inflammatory effects in treated asthmatics (Barnes and Pauwels, 1994;Oliver et al, 2001;Ohta et al, 2004). Our present results are consistent with such clinical observations because at 30 to 50 M theophylline consistently achieved significant inhibition of the release of both TNF-␣ and IL-6, both cytokines being important mediators in the pathophys- (Gosset et al, 1991;Broide et al, 1992;Barnes et al, 1998;Thomas, 2001).…”

Adverse Drug Reaction Profile of Drugs Used in Patients Suffering from Respiratory Disorders in a Tertiary Care Centre of Hyderabad India

“…The 5 most frequently observed adverse events were nausea (40 episodes, 1.05%), loss of appetite (22 episodes, 0.56%), hyperuricemia (16 episodes, 0.42%), palpitation (15 episodes, 0.39%) and increased alkaline phosphatase (11 episodes, 0.28%). [8] Pelletier et al in their study about 1 st line anti tubercular drugs found that the serious adverse reactions to antitubercular drugs were common and pyrizinamide induced hepatotoxicity and rash was significantly higher than for the other first-line anti-TB drugs. [9] Kheirollah Gholami et al found adverse drug reactions in 44 (53%) patients out of 83 patients receiving antitubercular drugs.…”