STIOLTO starts working in 5 minutes, and lasts for a full 24 hours, to address symptoms such as1:

Chest
tightness
Cough
Wheezing
Dyspnea

STIOLTO RESPIMAT is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms.

In one study, STIOLTO RESPIMAT showed twice the improvement in lung function (FEV1) compared with SPIRIVA RESPIMAT (tiotropium bromide) Inhalation Spray.1

TONADO 1: Significant 117-mL increase in FEV1 AUC0-3h vs SPIRIVA RESPIMAT (P≤0.0001) and 123-mL improvement vs STRIVERDI RESPIMAT (olodaterol) (P≤0.0001)

TONADO 2: Significant 103-mL improvement in FEV1 AUC0-3h vs SPIRIVA RESPIMAT (P≤0.0001) and 132-mL improvement vs STRIVERDI RESPIMAT (olodaterol) (P≤0.0001)

AUC0-3h=area under the curve from 0-3 h.

The increased bronchodilator effects of STIOLTO compared with tiotropium 5 mcg were maintained throughout the 52-week treatment period.1

Co-primary endpoints at 24 weeks in patients with GOLD 2–4: in TONADO 1, 71-mL improvement in trough FEV1 response vs SPIRIVA RESPIMAT (P≤0.0001). 117-mL improvement in FEV1 AUC0-3h vs SPIRIVA RESPIMAT (P≤0.0001) and a 123-mL improvement vs STRIVERDI RESPIMAT (P≤0.0001). In TONADO 2, trough FEV1 50-mL improvement vs SPIRIVA RESPIMAT (P≤0.0001); 88-mL improvement vs STRIVERDI RESPIMAT (P≤0.0001), FEV1 AUC0-3h 103-mL improvement vs SPIRIVA RESPIMAT (P≤0.0001); 132-mL improvement vs STRIVERDI RESPIMAT (P≤0.0001).1

STIOLTO RESPIMAT: adverse event profile comparable to monotherapy SPIRIVA RESPIMAT, the medication whose safety profile you already know1

The 52-week adverse event profile of STIOLTO is comparable to those of SPIRIVA RESPIMAT (tiotropium bromide) Inhalation Spray and olodaterol1

stiolto respimat (once daily) tiotropium (5 mcg once daily) olodaterol (5 mcg once daily) ADVERSE DRUG REACTION TREATMENT NASOPHARYNGITIS COUGH BACK PAIN n=1029 n (%) n=1033 n (%) n=1038 n (%) 128 (12.4) 40 (3.9) 37 (3.6) 121 (11.7) 45 (4.4) 19 (1.8) 131 (12.6) 31 (3.0) 35 (3.4)

STIOLTO had a lower discontinuation rate than either of its components. The discontinuation rate due to adverse events was 7.4% compared to 9% for tiotropium and 9.9% for olodaterol1

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.