Effect of add-on therapy of tiotropium in COPD treated with theophylline

Abstract

Background: Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insuffi cient evidence for the effi cacy of some combinations of long-acting bronchodilators. Objective: We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients. Methods: In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD. Results: Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV 1 ) 1.5 L [62.5% predicted]). FEV 1 in the combination group, but not in the theophylline alone, was signifi cantly increased at 4 (1.56 ± 0.13 L, p Ͻ 0.001) and 8 weeks (1.60 ± 0.13 L, p Ͻ 0.001) from the baseline (1.40 ± 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was signifi cantly improved after 4 (p Ͻ 0.01) and 8 weeks (p < 0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV 1 . Conclusion: Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefi t of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.

Theophylline for the management of respiratory disorders in adults in the 21st century: A scoping review from the American College of Clinical Pharmacy Pulmonary Practice and Research Network

“…Safety outcomes were reported in 17 studies . 27,29,36,38,[40][41][42][43]45,[47][48][49]51,52,[55][56][57] The adverse effects observed were consistent with those reported with theophylline. This included gastrointestinal (nausea, diarrhea, vomiting, heartburn, appetite suppression) and neurologic (headache, insomnia, dizziness, tremors) adverse effects.…”

“…51 In one outpatient study in Japan, the addition of tiotropium to theophylline improved dyspnea and pulmonary function in patients with COPD. 49 The addition of theophylline to salmeterol treatment offered no advantage over salmeterol alone in outpatients with well-controlled COPD. 39 One study of outpatients in Italy found that adding oral theophylline to a combination of formoterol and tiotropium did not provide significant further improvement in lung function and dyspnea in patients with stable COPD.…”

“…27,29, Sixteen studies were conducted in the outpatient setting, 27,36,40,41,43,[45][46][47][48][49]51,52,[54][55][56][57] one study was conducted in the inpatient setting, 53 three studies were conducted in both inpatient and outpatient settings, 42,44,50 and four studies did not specify their treatment setting. 29,[37][38][39] The severities and classifications of COPD included: unreported (n = 7), 27,[44][45][46]51,56,57 moderate-to-severe (n = 3), 37,38,41 well-controlled or stable (n = 3), 39,40,49 mild-to-severe (n = 2), 29,36 International Classifications of Diseases codes (n = 2), 50,54 moderate (n = 1), 52 acute exacerbations (n = 1), 42 GOLD stages II and III (n = 1), 47 GOLD stages III and IV…”

“…(n = 1), 43 GOLD groups B and D (n = 1), 55 COPD with comorbid sepsis (n = 1), 53 and spirometry alone (n = 1). 48 The clinical practice guidelines referenced were: GOLD (n = 11), 37,[40][41][42][43]45,47,49,[54][55][56] unreported 27,29,44,46,48,50,52,53,57 and ATS (n = 4). 36,38,39,51 Significant heterogeneity was noted across treatment groups (ie, theophylline monotherapy, theophylline plus bronchodilator, theophylline plus ICS, etc) and all interventions are charted in Table 4.…”

Development of a chiral RP-HPLC method for identification of stereomers of newly synthesized xanthine-based hydrazide-hydrazone compound

“…Theophylline, also known as 1,3-dimethylxanthine, is a proven bronchodilator drug used in therapy for respiratory diseases such as asthma or chronic pulmonary obstructive disease (COPD) (Black et al 1990;Cazzola and Gabriella 2007;Majumdar and Sloan 2007a, b;Kawayama et al 2008;Korzycka and Górska 2008).…”