The safety of LAMA/LABA combination therapy for the ocular and urinary adverse effects in the COPD patients

Background: As a treatment of Chronic obstructive pulmonary disease (COPD), long-acting muscarinic antagonists (LAMA) and long-acting β2-agonists (LABA) combinations are effective. While LAMA may cause an increase in the intraocular pressure and urinary retention due to anticholinergic effects, the safety of LAMA/LABA has not been well established. Subjects and Methods: This study is a 3-period crossover study consists of 3 different LAMA/LABA combination treatments as follows; tiotropium/olodaterol (TIO/OLO), indacaterol maleate/glycopyrronium (IND/GLY), umeclidinium/vilanterol (UMEC/VI). Thirty subjects with COPD were recruited. They received each treatment for more than 1 month with a 7-day washout period. Urinary side effects were assessed using questionnaires and the residual urine volume measured by the urologist. Questionnaires included the International Prostate Symptom Score (I-PSS), Quality of life (QOL) score and the Overactive Bladder Symptom Score (OABSS). Also, the ocular side effects were assessed using the intraocular pressure, the pupillary diameter, the van Herick technique by the ophthalmologist. Results: LAMA/LABA combination did not significantly affect I-PSS, OABSS, the residual urine volume, intraocular pressure, the pupillary diameter and the van Herick grade compared with no medication. However, TIO/OLO significantly increased the OABSS and intraocular pressure compared with UMEC/VI (P=0.05 for the OABSS, P=0.01 for the intraocular pressure). While TIO/OLO increased these scores, any subjects did not need an emergency treatment. Conclusions: Our results showed the safety of the LAMA/LABA combination for the ocular and urinary adverse effects.