1.1. Adults

Ipratropium (Atrovent®), a short-acting, inhalational anticholinergic agent, is FDA-approved to manage bronchospasm associated with chronic bronchitis and emphysema, collectively known as chronic obstructive pulmonary disease (COPD). Ipratropium is considered a second-line agent in the treatment of asthma as the bronchodilatory effects seen with ipratropium are less than those seen with beta-adrenergic drugs. While not FDA approved, the Expert Panel 3 guidelines from the National Heart Lung and Blood Institute document benefit when multiple ipratropium doses are administered adjunctively with beta2-agonists in the emergency department to manage more severe acute asthma exacerbations, and the Global Initiative for Asthma (GINA) guidelines state that ipratropium may be considered an alternative bronchodilator in patients who experience adverse effects to short-acting beta2-agonists (e.g., tachycardia, arrhythmia, tremor). Additionally, ipratropium may be administered in conjunction with short-acting beta agonists, corticosteroids, or oxygen in patients with acute, life-threatening asthma exacerbations awaiting transfer to an acute care center. The “2020 Focused Updates to the Asthma Management Guidelines” do not address the use of short acting muscarinic antagonist agents. Ipratropium is available as a metered-dose, inhalation aerosol solution and is FDA-approved for use in adult COPD patients receiving an aerosol bronchodilator who continue to have bronchospasm and require a second bronchodilator.

Tiotropium (Spiriva®) is a long-acting, inhalational anticholinergic agent FDA-approved for long-term use in managing bronchospasm associated with COPD and reducing COPD exacerbations, as well as maintenance therapy for asthma. GINA guidelines state that tiotropium is recommended as Step 4 and 5 add-on therapy in adults, adolescents, and children 6 years of age or older with asthma and a history of exacerbations. Tiotropium is available as a dry inhalation powder in capsule form or aerosol solution for oral inhalation. Due to the compound’s extended duration of action, tiotropium is approved for only once daily administration.

Aclidinium (Tudorza Pressair®), is FDA-approved as long-term maintenance therapy for bronchospasm associated with COPD, is available as a breath-actuated dry powder inhaler and is dosed twice daily. Umeclidinium (Incruse Ellipta®), another breath-actuated inhalation powder, is also approved for long-term COPD maintenance treatment.

Ipratropium is also available in combination with albuterol as Combivent Respimat®, which is FDA- approved for use in adult COPD patients receiving an aerosol bronchodilator who continue to have bronchospasm and require a second bronchodilator. This propellant-free product provides a slow-moving mist to supply the active ingredients and has replaced the metered-dose inhaler which used chlorofluorocarbons to deliver medication (i.e., Combivent®). Combivent Respimat® requires only one actuation per dose compared to the older Combivent® product, which required two actuations per dose.

Combination therapy including umeclidinium (inhaled anticholinergic) plus the long-acting beta-2 agonist (LABA), vilanterol, marketed as Anoro Ellipta®, is FDA-approved for use in adults with COPD as maintenance therapy. This product is the first dual therapy bronchodilator available for once daily use. Three additional anticholinergic/LABA combination products, tiotropium/olodaterol (Stiolto Respimat®), glycopyrrolate/formoterol (Bevespi Aerosphere®), and aclidinium bromide/ formoterol (Duaklir Pressair®) are also FDA approved for COPD maintenance therapy.

Triple therapy with fluticasone (inhaled corticosteroid), umeclidinium (inhaled anticholinergic), and vilanterol (inhaled LABA), marketed as Trelegy Ellipta®, is the most recent inhaled anticholinergic combination therapy FDA-approved for use to manage COPD in adults who continue to have bronchospasm while treated with a bronchodilator and require a second bronchodilator. In September of 2020 it was approved for the maintenance treatment of asthma in patients 18 years of age and older.

In March of 2020 Sunovion Pharmaceuticals announced the discontinuation of Utibron Neohaler® (indacaterol/glycopyrrolate) and Seebri Neohaler® (glycopyrrolate). These products are no longer available in the United States as of April 1, 2020.

Recommended doses for anticholinergic MDI monotherapy and combination products are summarized in Tables 1 and 2, respectively. Dosages exceeding the approved recommendations will be reviewed.