Concomitant use of ipratropium and tiotropium in chronic obstructive pulmonary disease

To describe the current data evaluating the efficacy and safety of ipratropium used in combination with tiotropium in patients with chronic obstructive pulmonary disease.

A literature search using MEDLINE (1966-August 2012) and EMBASE (1973-August 2012) was conducted using the search terms ipratropium, tiotropium, combination drug therapy, and chronic obstructive pulmonary disease. References of identified articles were reviewed for additional relevant citations.

All English-language articles regarding the concomitant use of ipratropium and tiotropium were reviewed.

Two prospective randomized controlled trials have demonstrated increases in bronchodilation with ipratropium when added to maintenance tiotropium therapy, suggesting potential benefits during short-term, combined use. One study reported significantly higher peak forced expiratory volume in 1 second (FEV(1)) responses with both ipratropium (230 mL) and fenoterol (315 mL) compared to placebo (178 mL) when added to maintenance tiotropium. The peak response with fenoterol was significantly higher than with ipratropium (FEV(1) difference = 84 mL). Another study reported a mean difference in FEV(1) of 81 mL (95% CI 27 to 136) with albuterol versus placebo and a mean difference in FEV(1) of 68 mL (95% CI 3 to 132) with ipratropium versus placebo. The difference between albuterol and ipratropium when added to maintenance tiotropium was not significant. One large observational study reported a significantly higher risk of acute urinary retention in individuals receiving combination therapy with a short- and long-acting anticholinergic agent compared to those receiving monotherapy (OR 1.84; 95% CI 1.25 to 2.71). Individuals at highest risk were men and those with evidence of benign prostatic hypertrophy.

While ipratropium may provide spirometric improvements in lung function for patients receiving tiotropium maintenance therapy, the clinical significance of these improvements has not been documented and the risk of anticholinergic adverse effects is increased with combination therapy. Further studies evaluating the safety and efficacy of concomitant ipratropium and tiotropium are warranted before combination use can be recommended for select patients.