Stiolto Respimat (tiotropium bromide and olodaterol)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Approval Status:

Approved May 2015

Specific Treatments:

maintenance of chronic obstructive pulmonary disease

Therapeutic Areas

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General Information

Stiolto Respimat is a once-daily fixed-dose combination of tiotropium, a long acting muscarinic antagonist and olodaterol, a long-acting beta-agonist.

Stiolto Respimat is specifically indicated for the long-term, once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease.

Stiolto Respimat is supplied as a spray for oral inhalation. The recommended dose is two inhalations once-daily at the same time of the day. Do not use more than two inhalations every 24 hours. 

Clinical Results

FDA Approval

The FDA approval of Stiolto Respimat was based primarily on two 4-week dose-ranging trials and two confirmatory active-controlled 52-week trials (Trials 1 and 2).

Dose-Ranging Trials:

Dose selection for Stiolto Respimat was primarily based on trials for the individual components, tiotropium bromide and olodaterol. Dose selection was also supported by two randomized, double-blind, active-controlled, 4-week trials. In one trial in 232 patients with COPD, three tiotropium doses (1.25, 2.5, and 5 mcg) were given in combination with olodaterol 5 or 10 mcg and were evaluated compared to olodaterol monotherapy. Results demonstrated improvement in trough FEV1 for the combination when compared to olodaterol alone. The difference in trough FEV1 for the tiotropium bromide/olodaterol doses of 1.25/5, 2.5/5, and 5/5 mcg once daily from olodaterol 5 mcg were 0.054 L (95% CI 0.016, 0.092), 0.065 L (0.027, 0.103), and 0.084 L (0.046, 0.122), respectively. In the second trial in 360 patients with COPD, three olodaterol doses (2, 5, and 10 mcg) were given in combination with tiotropium 5 mcg and were evaluated compared to tiotropium monotherapy. The difference in trough FEV1 for the tiotropium/olodaterol doses of 5/2, 5/5, and 5/10 mcg once daily from tiotropium 5 mcg were 0.024 L (95% CI -0.029, 0.076), 0.033 L (-0.019, 0.085), and 0.057 L (0.004, 0.110), respectively. Results of these trials supported the evaluation of once-daily doses of tiotropium bromide/olodaterol 2.5/5 mcg and 5/5 mcg in the confirmatory trials.

Confirmatory Trials:

A total of 5,162 COPD patients (1029 receiving Stiolto Respimat, 1,038 receiving olodaterol 5 mcg, and 1,033 receiving tiotropium bromide 5 mcg) were studied in two confirmatory trials of Stiolto Respimat. Trials 1 and 2 were 52-week, replicate, randomized, double-blind, active controlled, parallel group trials that compared Stiolto Respimat to tiotropium 5 mcg and olodaterol 5 mcg. In these trials, all products were administered via the RESPIMAT inhaler. The trials enrolled patients 40 years of age or older with a clinical diagnosis of COPD, a smoking history of more than 10 pack-years, and moderate to very severe pulmonary impairment. All treatments were administered once daily in the morning. The primary endpoints were change from baseline in FEV1 AUC0-3hr and trough FEV1 after 24-weeks of treatment. In both Trials 1 and 2, Stiolto Respimat demonstrated significant improvements in FEV1 AUC0-3hr and trough FEV1 after 24 weeks compared to tiotropium 5 mcg and olodaterol 5 mcg. The increased bronchodilator effects of Stiolto Respimat compared to tiotropium 5 mcg and olodaterol 5 mcg were maintained throughout the 52-week treatment period. Stiolto Respimat displayed a mean increase in FEV1 from baseline of 0.137 L (range: 0.133-0.140 L) within 5 minutes after the first dose. Patients treated with Stiolto Respimat used less rescue medication compared to those treated with tiotropium 5 mcg and olodaterol 5 mcg. 

Side Effects

Adverse reactions associated with the use of Stiolto Respimat may include, but are not limited to, the following:

  • nasopharyngitis
  • cough
  • back pain

Mechanism of Action

Stiolto Respimat is a once-daily fixed-dose combination of tiotropium and olodaterol. Tiotropium is a long-acting, muscarinic antagonist which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3-receptors at the smooth muscle leading to bronchodilation. Olodaterol is a long-acting beta2-adrenergic agonist (LABA). The compound exerts its pharmacological effects by binding and activation of beta2-adrenoceptors after topical administration by inhalation. Activation of these receptors in the airways results in a stimulation of intracellular adenyl cyclase, an enzyme that mediates the synthesis of cyclic-3’, 5’ adenosine monophosphate (cAMP). Elevated levels of cAMP induce bronchodilation by relaxation of airway smooth muscle cells.

Additional Information

For additional information regarding the maintenance treatment of COPD or Stiolto Respimat, please visit http://www.boehringer-ingelheim.com/