STIOLTO RESPIMAT can reduce exacerbations and exacerbation-related hospitalizations independent of ICS use1,2

Tiotropium, an active ingredient of STIOLTO, can reduce the risk of exacerbations by 31% compared with placebo1,2

Tiotropium can reduce the risk of exacerbation-related hospitalizations by 27% compared with placebo2

Reduction in risk compared with with placebo1,2

HR=0.69 (95% CI, 0.625, 0.769);
P<0.0001 (log-rank test)

STUDY DESIGN:
Tiotropium vs Placebo, time to first COPD exacerbation.

STUDY DESIGN: In a 1-year, randomized, double-blind, parallel-group study, 3991 patients with COPD were evaluated to compare tiotropium bromide, a component of STIOLTO RESPIMAT, and placebo on coprimary endpoints: change in trough FEV1 from treatment Day 1 to Day 337 and time to first COPD exacerbation. Secondary endpoints were change in trough FEV1 at Days 29, 169, and 337; the number of exacerbations per patient, the number of patients with ≥1 exacerbation; and the time to first exacerbation-related hospitalization. Exacerbations were defined as complex respiratory events or symptoms that lasted ≥3 days and required treatment with antibiotics and/or systemic corticosteroids, or prompted the investigator to change the patient’s regular respiratory medication.1,2

Major inclusion criteria included patients diagnosed with COPD, 40 years of age or over, a prebronchodilator FEV1 of ≤60% of predicted normal, a ratio of FEV1 to FVC of ≤70%, and a smoking history of 10 pack-years or more.1,2

STIOLTO RESPIMAT showed a 7% reduction in the rate of exacerbations vs SPIRIVA RESPIMAT (tiotropium bromide) Inhalation Spray1,3

The P-value of 0.049 did not meet the prespecified significance level of 0.013

Reduction in rate compared with SPIRIVA RESPIMAT1,3

RR=0.93 (99% CI: 0.85, 1.02);
P=0.049

STIOLTO (CI: 0.84-0.96)*

SPIRIVA (CI: 0.90-1.03)*

*99% CI, prespecified level of significance.

STUDY DESIGN:
Tiotropium + olodaterol vs Tiotropium, rate of moderate and severe COPD exacerbations.

STUDY DESIGN: A 52-week, double-blind, parallel-group trial, including COPD (chronic obstructive pulmonary disease) patients with a history of exacerbations randomized 1:1 using a randomized block design to receive STIOLTO RESPIMAT (tiotropium bromide and olodaterol) 5mcg-5 mcg or SPIRIVA® RESPIMAT® (tiotropium bromide) 5 mcg once daily. The primary endpoint was the rate of moderate and severe COPD exacerbations, at a significance level of 0.01. A total of 7903 patients were randomized in the study and 7880 were treated; 3939 received STIOLTO and 3941 received SPIRIVA.3

IMPORTANT SAFETY INFORMATION

WARNING: ASTHMA-RELATED DEATH

Long‑acting beta2‑adrenergic agonists (LABA) such as olodaterol, one of the active ingredients in STIOLTO RESPIMAT, increase the risk of asthma‑related death. Data from a large, placebo‑controlled US study that compared the safety of another long‑acting beta2‑adrenergic agonist (salmeterol) with placebo added to usual asthma therapy showed an increase in asthma‑related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of all LABA, including olodaterol, one of the active ingredients in STIOLTO RESPIMAT. The safety and efficacy of STIOLTO RESPIMAT in patients with asthma have not been established. STIOLTO RESPIMAT is not indicated for the treatment of asthma.

INDICATION AND LIMITATIONS OF USE

Stiolto Respimat (tiotropium bromide and olodaterol) Inhalation Spray is a combination of tiotropium, an anticholinergic, and olodaterol, a long‑acting beta2‑adrenergic agonist (LABA), indicated for the long‑term, once‑daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Important Limitations of Use

STIOLTO is NOT indicated to treat acute deterioration of COPD and is not indicated to treat asthma.

CONTRAINDICATION

All LABA are contraindicated in patients with asthma without use of a long‑term asthma control medication. STIOLTO is contraindicated in patients with hypersensitivity to tiotropium, ipratropium (atropine derivatives), olodaterol, or any component of this product.

In clinical trials and postmarketing experience with tiotropium, immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash have been reported. Hypersensitivity reactions were also reported in clinical trials with STIOLTO.

WARNINGS AND PRECAUTIONS

STIOLTO should not be initiated in patients with acutely deteriorating COPD, which may be a life‑threatening condition, or used as rescue therapy for acute symptoms. Acute symptoms should be treated with an inhaled short‑acting beta2‑agonist. Patients who have been taking inhaled, short‑acting beta2‑agonists on a regular basis should discontinue the regular use of these drugs and use them only for acute respiratory symptoms.

STIOLTO should not be used more often or at higher doses than recommended, or in conjunction with other LABA as an overdose may result.

Immediate hypersensitivity reactions, including urticaria, angioedema, rash, bronchospasm, anaphylaxis, or itching may occur after administration of STIOLTO. If such a reaction occurs, discontinue therapy with STIOLTO and consider alternative treatments. Patients with a history of hypersensitivity reactions to atropine or its derivatives should be closely monitored for similar hypersensitivity reactions to STIOLTO.

If paradoxical bronchospasm occurs, STIOLTO should be discontinued immediately.

STIOLTO can produce a clinically significant cardiovascular effect in some patients, as measured by increases in pulse rate, systolic or diastolic blood pressure, and/or symptoms. If such effects occur, STIOLTO may need to be discontinued.

Use caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, in patients with known or suspected prolongation of the QT interval, and in patients who are unusually responsive to sympathomimetic amines.

Use with caution in patients with narrow‑angle glaucoma. Instruct patients to contact a physician immediately if signs or symptoms of acute narrow‑angle glaucoma develop (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema).

Use with caution in patients with urinary retention, which can be associated with symptoms like difficulty passing urine and painful urination in patients with prostatic hyperplasia or bladder‑neck obstruction. Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Patients with moderate to severe renal impairment (creatinine clearance of <60 mL/min) treated with STIOLTO should be monitored closely for anticholinergic side effects.

Be alert to hypokalemia, which has the potential to produce adverse cardiovascular effects. Be alert to hyperglycemia.

ADVERSE REACTIONS

The most common adverse reactions with STIOLTO (>3% incidence and higher than any of the comparators — tiotropium and/or olodaterol) were: nasopharyngitis, 12.4% (11.7%/12.6%), cough, 3.9% (4.4%/3.0%), and back pain, 3.6% (1.8%/3.4%).

DRUG INTERACTIONS

  • Use caution if administering adrenergic drugs because sympathetic effects of olodaterol may be potentiated.
  • Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate any hypokalemic effect of olodaterol.
  • Beta agonists, such as olodaterol, can acutely worsen the ECG changes and/or hypokalemia that may result from administration of non‑potassium sparing diuretics. The action of adrenergic agents on the cardiovascular system may be potentiated by monoamine oxidase inhibitors or tricyclic antidepressants or other drugs known to prolong the QTc interval. Therefore beta‑agonists should be used with extreme caution in patients being treated with these drugs. Drugs that prolong the QTc interval may be associated with an increased risk of ventricular arrhythmias.
  • Beta‑blockers should be used with caution as they can inhibit the therapeutic effect of beta agonists which may produce severe bronchospasms in patients with COPD. However, under certain circumstances, e.g. as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta‑blockers in patients with COPD. In this setting, cardio selective beta‑blockers could be considered, although they should be administered with caution.
  • Avoid co‑administration of STIOLTO with other anticholinergic‑containing drugs as this may lead to an increase in anticholinergic adverse effects.

STIOLTO is for oral inhalation only. The STIOLTO cartridge is only intended for use with the STIOLTO RESPIMAT inhaler.

Inform patients not to spray STIOLTO into the eyes.

CL-STO-0043 6.23.2016

Please see full Prescribing Information, including boxed WARNING, Medication Guide, and Instructions for Use.

References: 1. STIOLTO RESPIMAT [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2018. 2. Bateman ED, Tashkin D, Siafakas N, et al. A one-year trial of tiotropium Respimat® plus usual therapy in COPD patients. Respir Med. 2010;104(10):1460-1472. 3. Calverley P, Anzueto A, Carter K, et al. Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active controlled trial. Lancet Respir Med. 2018;6(5):337-344.