Evaluation of efficacy and safety of doxofylline 800mg sustained release tablet in treatment of patients with COPD: an open label, prospective and RCT

Prakash Narayan Khandelwal, Syed H. Maaz, Dhammraj M. Borade


Background: COPD is a major cause of health care burden worldwide and leading cause of death that is increasing in prevalence. Methylxanthines are used in the treatment of patients with asthma and COPD. Doxofylline (methylxanthine) shows improved disease control, reduced total daily dose of inhaled b2 agonists and improved patient compliance.

Methods: This was a prospective, open labelled, randomized, two-arm, parallel group, controlled, clinical trial. 115 patients were randomized to two groups. Patients in group A received tablet doxofylline 400mg BD whereas patients in group B received tablet doxofylline 800mg SR for 4 weeks. Primary outcome measure of trial was change in FEV1 and secondary outcome measure were change in FVC/FEV1, change in symptoms score, effect on health-related quality of life (HRQOL) and safety of study medication.

Results: At 4 week the FEV1increase by 13.028% and 17.647% in group A and B respectively. In group A FEV1/FVC increase by 5.79% and in group B it increases by 9.57% at 4 weeks. The symptom score of cough decrease by 77.35% and 97.43% in group A and group B respectively at 4 weeks. In group A shortness of breath decrease by 77.60% and in group B it decreases by 95.90% at 4 weeks. Tightness in chest decrease by 86.29% and 98.40% in group A and group B respectively at 4 weeks.

Conclusions:Doxofylline 800mg sustained release tablet provided significantly greater improvement in FEV1, symptomatic control and health related quality of life compared to doxofylline 400mg.



Chronic obstructive pulmonary disease, Doxofylline, Sustained release formulation

Full Text:



Khan MH, Javaid A. Bronchodilator response to nebulized salbutamol in elderly patients with stable COPD. JPMI. 2007;21(3):222-26.

Richard L, ZuWallack RL, Mahler DA, Reily D, Church N, Emmett A, Rickard K, et al. Salmeterol plus theophylline combination therapy in the treatment of COPD. Chest. 2010;119:1661-70.

Jindal SK. Emergence of chronic obstructive pulmonary disease as an epidemic in India. 2006;124:619-30.

Shrestha R, Shakya R. Comparison of bronchodilator effect of salbutamol delivered via MDI and DPI in COPD patients. SAARC J. Tuber. Lung Dis. HIV/AIDS. 2009;6(2):22-30.

Bagnato GF. Tolerability of doxofylline in maintenance therapy of pediatrics patient with bronchial asthma. Eur Rev Med Pharmacol Sci. 1999;3:255-66.

Gladysheva ES, Malhotra A, Owens RL. Influencing the decline of lung function in COPD: use of pharmacotherapy. Int J Chron Obstruct Pulmon Dis. 2010;5:153-64.

Sharma HL, Sharma KK. Principles of Pharmacology. In: Sharma HL, Sharma KK, editors. Drug therapy of Bronchial Asthma. 1st Ed. Hyderabad: Paras medical publishers; 2008:658-666.

Bierman CW, Pierson WE, Shapiro CG, Furukawa CT. Is a uniform round-the-clock theophylline blood level necessary for optimal asthma therapy in the adolescent patient? Am J Med. 1988;85(1):17-20.

Neuenkirchen H, Wilkens JH, Oellerich M, Sybrecht GW. Nocturnal asthma: effect of a once per evening dose sustained release theophylline. Eur J Respir Dis. 1985;66(3)196-204.

Halbert RJ, Isonaka S, Dorothy G, Iqbal A. Interpreting COPD prevalence estimate: what is the true burden of disease? Chest. 2003;123:1684-92.

Kurli S, Sowmya DC, Sumalata.C. Comparative study of efficacy and adverse effect profile of theophylline and etofylline combination verses doxofylline in patients with COPD. Sch. J App Med Sci. 2015;3(1E):310-17.

Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS; GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Am J Respir Crit Care Med. 2001;163:1256-76.

Miravitiles M. Maintenance therapy and guidelines for mild to moderate chronic obstructive pulmonary disease. European Respiratory Disease. 2010;6:20-3.

Dini FL, Doxofylline CR. A new generation xanthine bronchodilator devoid of major cardiovascular adverse effects. Cur Med Res Opin. 2001;16(4):258-68.

Cogo R, Castronuovo A. Effect of oral doxofylline on inflammatory changes and altered cell proliferation in chronic obstructive pulmonary disease. Eur Rev Med Pharmacol Sci. 2000;4:15-20.

Celli BR, MacNee W. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004;23:932-46.

Duque GA. Doxfylline. An option to have in mind in the management of asthma and COPD. European Bulletin of Drug Research. 2007;15(1):1-7.

Jindal SK, Gupta D, Aggarwal AN. Guidelines for management of chronic obstructive pulmonary disease (COPD) in India: a guide for physicians (2003). Indian J Chest Dis Allied Sci. 2004;46:137-53.

Mirabelli S, Dini FL. Pulmonary function test in chronic heart failure and chronic airway obstruction. Effect of doxofylline. Rev. Colomb. Neumolog. 2000;12:S22.

Villani F, DeMaria P, Ronchi E, Galimberti M. Oral doxofylline in patients with chronic obstructive pulmonary disease. Int. J. Clin. Pharm. Ther. 1997;35(3):207-11.

Goldstein MF, Chervinsky P. Efficacy and safety of doxofylline compared to theophylline in chronic reversible asthma. A double-blind randomized placebo-controlled multi-centre clinical trial. Med Sci Monit. 2002;8(4):CR297-304.

Sankar J, Lodha R, Kabra SK. Doxofylline: The next generation methylxanthines. Indian J of Pediatrics. 2008;(3)75:251-4.