By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved the first once-a-day, nebulized bronchodilator to treat COPD. Revefenacin is a long-acting muscarinic antagonist (LAMA) that is marketed as Yupelri.


Revefenacin should be used to help patients with COPD.1


The recommended dose is 175 mcg (one 3 mL vial) with a standard jet nebulizer and a mouthpiece connected to an air compressor.1


Revefenacin is the only once-daily LAMA option for patients who cannot or choose not to use a handheld device.


Coadministration of revefenacin is not recommended with inhibitors of the uptake transporters (OATP1B1, OATP1B3) such as rifampicin and cyclosporine, as this may lead to more exposure to the active metabolite.1 No one has conducted a study of revefenacin use in pregnant women, although no fetal harm has been identified in animal studies.1 Revefenacin shares the same class warning with other antimuscarinic drugs (e.g., worsening of narrow-angle glaucoma and urinary retention). Immediate hypersensitivity reactions may occur with revefenacin administration.1


The efficacy of revefenacin was confirmed in two 12-week, randomized, double-blind, placebo-controlled trials that included 812 subjects with moderate-to-severe COPD.1-3 Subjects at screening demonstrated a mean postbronchodilator percent-predicted FEV1 of 55% (range, 10-90%) and FEV1/FVC ratio of 0.54 (range, 0.3-0.7). Thirty-seven percent of subjects were taking a long-acting beta-agonist (LABA) alone or in combination with an inhaled corticosteroid at study entry and remained on concomitant therapy throughout the study periods. Subjects were randomized to revefenacin (175 mcg daily) or placebo. The primary endpoint was change from baseline in trough (predose) FEV1 at day 85. The least square mean differences from placebo for FEV1 were 146 mL and 147 mL in the two studies. The St. George’s Respiratory Questionnaire also was assessed. This 50-item questionnaire measures the quality of life in patients with airway obstruction disease on three domains: symptoms, activity, and psychosocial impact.4 Responders were defined as a score improvement of ≥ 4 units (on a scale from 0 to 100).

The responder rates were 49% and 45% for revefenacin compared to 34% and 39% for placebo, respectively. In an open-label, 52-week safety study vs. tiotropium (dose = 18 mcg; n = 1,055), the frequency and severity of adverse events were similar.3


The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) recommends LAMAs and LABAs, with or without an inhaled corticosteroid, as important components for the management of moderate to very severe COPD.5 These treatments significantly improve lung function, dyspnea, and health status and reduce exacerbation rates. LAMAs appear to reduce exacerbation rates better than LABAs and are better in combination than as monotherapy.

The cost for revefenacin is $41.20 for a 3 mL vial or $1,236 for a 30-day supply.


  1. Mylan Specialty, L.P. Yupelri Prescribing Information, November 2018. Available at: Accessed Feb. 8, 2019.
  2. Efficacy study of nebulized TD-4208 for chronic obstructive pulmonary disease (COPD). Available at: Accessed Feb. 8, 2019.
  3. A 52-week parallel group safety study of TD-4208 in chronic obstructive pulmonary disease (COPD). Available at: Accessed Feb. 8, 2019.
  4. American Thoracic Society. St. George’s Respiratory Questionnaire. Available at: Accessed Feb. 8, 2019.
  5. Global Initiative for Chronic Obstructive Pulmonary Disease. Pocket Guide to COPD Diagnosis, Management, and Prevention. Available at: Accessed Feb. 8, 2019.