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
for STIOLTO RESPIMAT

CONTRAINDICATION

Use of a LABA, including STIOLTO RESPIMAT, without an inhaled corticosteroid (ICS) is contraindicated in patients with asthma.

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.

INDICATION for STIOLTO RESPIMAT

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 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.


WARNINGS AND PRECAUTIONS

LABA as monotherapy (without an ICS), for asthma increases the risk of asthma-related death, and in pediatric and adolescent patients,
increases the risk of asthma-related hospitalizations.

Do not initiate STIOLTO 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.

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

If immediate hypersensitivity reactions occur, such as urticaria, angioedema, rash, bronchospasm, anaphylaxis, or itching, discontinue
STIOLTO at once and consider alternative treatment. 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, discontinue STIOLTO immediately and institute alternative therapy.

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.

Use with caution in patients with urinary retention especially 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) should be monitored closely for
anticholinergic side effects.

Be alert to hypokalemia and hyperglycemia.

ADVERSE REACTIONS

The most common adverse reactions with STIOLTO (>3% incidence and higher than an active control) 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.
  • Use with caution in patients taking non–potassium-sparing diuretics, as the ECG changes and/or hypokalemia may worsen with
    concomitant beta-agonists.
  • 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, STIOLTO should be used with extreme caution
    in patients being treated with these drugs. Use beta-blockers with caution as they not only block the therapeutic effects of
    beta-agonists, but may produce severe bronchospasm in patients with COPD.
  • 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 as this may cause blurring of vision and pupil dilation.

CL-STO-100021 6.5.2019

Please see accompanying full Prescribing Information, Patient Information, and Instructions for Use for STIOLTO RESPIMAT.

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.