SPIRIVA RESPIMAT Significantly Improves Lung Function (Peak FEV1(0-3h))1

Adding SPIRIVA RESPIMAT to ICS/LABA significantly increased peak FEV1(0-3h) at 12 weeks1,3

When on a background treatment of ICS/LABA, adding SPIRIVA RESPIMAT significantly increased peak FEV1(0-3h) as measured at 12 weeks in adolescent patients aged 12–17 years1

Asthma Improved FEV₁ Lung Function in Adult Patients on an ICS + LABA Asthma Improved FEV₁ Lung Function in Adult Patients on an ICS + LABA
  • In the same pivotal trial, SPIRIVA RESPIMAT + ICS + LABA showed a 115-mL (P=0.0509 [95% CI: 0, 231 mL]) greater change in trough FEV1 vs placebo + ICS + LABA (345 mL vs 230 mL, respectively) at 12 weeks in adolescent patients with severe asthma2*
  • 83% of patients in the adolescent trial were on medium- or high-dose ICS + LABA2

Study Design: Trial 1 was a 12-week, randomized, double-blind, parallel-group comparison of SPIRIVA RESPIMAT 1.25 mcg/puff (2 puffs, 1 time each day) on a background of medium-dose ICS (200-400 μg budesonide or equivalent in patients aged 12-14 years and 400-800 mcg budesonide or equivalent in patients aged 15-17 years) or high-dose ICS (>400 μg budesonide or equivalent in patients aged 12-14 years and 800-1600 μg budesonide or equivalent in patients aged 15-17 years) + ≥1 (with high-dose ICS) or ≥2 (with medium-dose ICS) controller medications (eg, LABA) and placebo on a background of medium- or high-dose ICS + ≥1 controller medication (eg, LABA). The primary endpoint was change in FEV1(0-3h) from baseline. Study participants were aged 12-17 years with symptomatic asthma despite use of ICS + ≥1 controller medication(s).2

*This result was not statistically significant.2

Medium-dose ICS: 400 mcg to 800 mcg budesonide or equivalent.2

High-dose ICS: 800 mcg to 1600 mcg budesonide or equivalent.2

Add SPIRIVA RESPIMAT for proven efficacy1,4

When on a background treatment of ICS, adding SPIRIVA RESPIMAT significantly increased peak FEV1(0-3h) and trough FEV1 vs placebo at 24 weeks in adult patients.1,4

Trial 2

Asthma Improved Peak FEV₁ Lung Function, SPIRIVA RESPIMAT Trial 2 Asthma Improved Trough FEV₁ Lung Function, SPIRIVA RESPIMAT Trial 2 Asthma Improved Trough FEV₁ Lung Function, SPIRIVA RESPIMAT Trial 2

Trial 3

SPIRIVA RESPIMAT + ICS and Salmeterol + ICS Increased Peak FEV1(0-3h) and Trough FEV1 as Measured vs Placebo + ICS at 24 Weeks in Adult Patients1,3

210 mL
increase in peak FEV1(0-3h) for SPIRIVA RESPIMAT + ICS vs placebo + ICS (P <0.0001 [95% CI: 160, 260 mL])
176 mL
increase in peak FEV1(0-3h) for salmeterol + ICS vs placebo + ICS (P<0.0001 [95% CI: 124, 229 mL])
180 mL
increase in trough FEV1(0-3h) for SPIRIVA RESPIMAT + ICS vs placebo + ICS (P <0.0001 [95% CI: 120, 230 mL])
106 mL
increase in trough FEV1(0-3h) for salmeterol + ICS vs placebo + ICS (P=0.0002 [95% CI: 50, 162 mL])
  • These trials were not designed to test the noninferiority of SPIRIVA RESPIMAT to salmeterol. Salmeterol efficacy was assessed between salmeterol + ICS vs placebo + ICS. Comparisons between SPIRIVA RESPIMAT and salmeterol cannot be made3
  • Study participants were adult patients with moderate asthma taking medium-dose ICS1,3*
  • Improvements in peak FEV1(0-3h) and trough FEV1 were independent of underlying allergic status3

Study Design: Trials 2 and 3 were randomized, double-blind, placebo-controlled, parallel-group comparisons of maintenance treatment on SPIRIVA RESPIMAT, 1.25 mcg/puff (2 puffs, 1 time each day), with background treatment of at least medium-dose ICS; SPIRIVA RESPIMAT, 2.5 mcg/puff (2 puffs, 1 time each day), with background treatment of at least medium-dose ICS; salmeterol, 50 mcg (twice daily), with background treatment of at least medium-dose ICS; and placebo, with background treatment of at least medium-dose ICS, for 24 weeks. The coprimary endpoints were change from pretreatment baseline in peak FEV1(0-3h) and change from pretreatment baseline in trough FEV1 at week 24. Study participants were not current smokers, aged 18 to 75 years, who had symptomatic asthma despite use of medium-dose ICS.1*


*Medium-dose ICS=400 mcg to 800 mcg budesonide or equivalent.1

SPIRIVA RESPIMAT is the only LAMA for asthma proven to reduce exacerbations in adults1

SPIRIVA RESPIMAT reduced the rate of exacerbations over 24 weeks in Trials 2 and 31,3

Trial 2

68%
rate reduction vs placebo
(RR: 0.32 [95% CI: 0.20, 0.51])

Trial 3

30%
rate reduction vs placebo
(RR: 0.70 [95% CI: 0.46, 1.08])*

In Trials 2 and 3, an asthma exacerbation was defined as an episode of progressive increase in ≥1 asthma symptom(s), eg, shortness of breath, cough, wheezing, chest tightness, or a combination of these symptoms; or a 30% decrease in best morning peak expiratory flow (PEF) for ≥2 consecutive days that required initiation or increase in treatment with systemic steroids for ≥3 days.1 See Study Design for Trials 2 and 3 below.


Study Design: Trials 2 and 3 were randomized, double-blind, placebo-controlled, parallel-group comparisons of SPIRIVA RESPIMAT 1.25 mcg/puff (2 puffs, 1 time each day) maintenance treatment on a background of at least medium-dose ICS (400 mcg-800 mcg budesonide or equivalent); SPIRIVA RESPIMAT 2.5 mcg/puff (2 puffs, 1 time each day), medium-dose ICS; salmeterol 50 mcg (twice daily), with background treatment of at least medium-dose ICS; or placebo with background treatment of at least medium-dose ICS, for 24 weeks. The coprimary endpoints were change from pretreatment baseline in peak FEV1(0-3h) and change from pretreatment baseline in trough FEV1 at week 24. Study participants were non-current smokers aged 18–75 years with symptomatic asthma despite use of medium-dose ICS. Additional efficacy measures included the mean rate of asthma exacerbations (events), Asthma Control Questionnaire (ACQ), and Asthma Quality of Life Questionnaire (AQLQ). In Trial 2, the mean rate of events for exacerbations in SPIRIVA RESPIMAT 2.5 mcg + ICS (n=259) and placebo + ICS (n=265) were 0.08 and 0.24, respectively. In Trial 3, the mean rate of events for exacerbations in SPIRIVA RESPIMAT 2.5 mcg + ICS (n=256) and placebo + ICS (n=253) were 0.13 and 0.18, respectively. These trials were not powered to demonstrate noninferiority of SPIRIVA RESPIMAT to salmeterol, and comparisons between SPIRIVA RESPIMAT and salmeterol cannot be made. Salmeterol efficacy was assessed against placebo on a background of ICS.1,3

*This result was not statistically significant.3

Add SPIRIVA RESPIMAT for pediatric efficacy1

When on a background treatment of at least ICS, adding SPIRIVA RESPIMAT significantly increased peak FEV1(0-3h) as measured at 24 weeks in pediatric patients aged 6 to 11 years1,4

Improved FEV₁ Lung Function in Pediatric Asthma Patients, SPIRIVA RESPIMAT Improved FEV₁ Lung Function in Pediatric Asthma Patients, SPIRIVA RESPIMAT
  • In the same pivotal 48-week trial, SPIRIVA RESPIMAT + ICS showed a 116-mL (P=0.0012 [95% CI: 46, 186 mL]) greater change in trough FEV1 vs placebo + ICS (272 mL and 156 mL, respectively) at week 24 in pediatric patients aged 6 to 11 years with moderate asthma.1,4

Study Design: The 48-week pediatric trial was a randomized, double-blind, parallel-group comparison of SPIRIVA RESPIMAT, 1.25 mcg/puff (2 puffs, 1 time each day), with background treatment of at least ICS; and placebo, with background treatment of at least ICS, over 48 weeks. The primary efficacy endpoint was change from pretreatment baseline in peak FEV1(0-3h) at week 24. Study participants were aged 6 to 11 years and had moderate asthma despite use of at least ICS.1,4

When on a background treatment of at least ICS, adding SPIRIVA RESPIMAT increased peak FEV1(0-3h) as measured at 12 weeks in pediatric patients aged 6 to 11 years1,5

Increased Peak FEV₁ Lung Function in Pediatric Asthma Patients, SPIRIVA RESPIMAT Increased Peak FEV₁ Lung Function in Pediatric Asthma Patients, SPIRIVA RESPIMAT
  • In the same pivotal 12-week trial, SPIRIVA RESPIMAT + ICS + LABA showed an 18-mL (P=0.5898 [95% CI: -48, 85 mL]) greater change in trough FEV1 vs placebo + ICS + LABA (154 mL and 136 mL, respectively) at week 12 in pediatric patients aged 6 to 11 years with severe asthma.1,4

Study Design: The 12-week pediatric trial was a randomized, double-blind, parallel-group comparison of SPIRIVA RESPIMAT, 1.25 mcg/puff (2 puffs, 1 time each day), with background treatment of ICS plus ≥1 controller medications; and placebo with background treatment of ICS plus ≥1 controller medications, over 12 weeks. The primary efficacy endpoint was change from pretreatment baseline in peak FEV1(0-3h). Study participants were aged 6 to 11 years and had severe asthma despite use of ICS plus ≥1 controller medications.1,5†

*This result was not statistically significant.5

LABA, and/or LTRA (leukotriene receptor antagonist), and/or sustained-release theophylline.5

ICS=inhaled corticosteroid; LABA=long-acting beta2-agonist; FEV1=forced expiratory volume in 1 second; FEV1(0-3h)= peak FEV1 within 3 hours postdosing; CI=confidence interval; RR=rate ratio.

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IMPORTANT SAFETY INFORMATION for SPIRIVA HANDIHALER and SPIRIVA RESPIMAT

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INDICATIONS

SPIRIVA RESPIMAT, 1.25 mcg, is a bronchodilator indicated for the long-term, once-daily, maintenance treatment of asthma in patients 6 years of age and older.

SPIRIVA RESPIMAT, 2.5 mcg, and SPIRIVA HANDIHALER are indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, and for reducing COPD exacerbations.

SPIRIVA is not indicated for relief of acute bronchospasm.

Important Safety Information

SPIRIVA is contraindicated in patients with a history of hypersensitivity to tiotropium, ipratropium, or any component of either product. Immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash have been reported.

SPIRIVA is intended as a once-daily maintenance treatment and should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. In the event of an attack, a rapid-acting beta2‑agonist should be used.

More Important Safety Information

Important Safety Information (continued)

Immediate hypersensitivity reactions, including urticaria, angioedema (swelling of lips, tongue, or throat), rash, bronchospasm, anaphylaxis, or itching may occur after administration of SPIRIVA. If such a reaction occurs, discontinue SPIRIVA at once and consider alternative treatments. Given the similar structural formula of atropine to tiotropium, patients with a history of hypersensitivity reactions to atropine or its derivatives should be closely monitored for similar hypersensitivity reactions to SPIRIVA.

SPIRIVA HANDIHALER should be used with caution in patients with severe hypersensitivity to milk proteins.

Inhaled medicines, including SPIRIVA, may cause paradoxical bronchospasm. If this occurs, it should be treated with an inhaled short‑acting beta2‑agonist, such as albuterol. Treatment with SPIRIVA should be stopped and other treatments considered.

SPIRIVA should be used with caution in patients with narrow‑angle glaucoma. Prescribers and patients should be alert for signs and symptoms of acute narrow‑angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Since dizziness and blurred vision may occur with the use of SPIRIVA, caution patients about engaging in activities such as driving a vehicle, or operating appliances or machinery.

SPIRIVA should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination), 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) and treated with SPIRIVA should be monitored closely for anticholinergic side effects.

The most common adverse reactions >3% incidence and higher than placebo with SPIRIVA RESPIMAT (placebo) in COPD trials were pharyngitis 11.5% (10.1%), cough 5.8% (5.5%), dry mouth 4.1% (1.6%), and sinusitis 3.1% (2.7%).

The most common adverse reactions >2% incidence and higher than placebo with SPIRIVA RESPIMAT (placebo) in asthma trials in adults were pharyngitis 15.9% (12.4%), headache 3.8% (2.7%), bronchitis 3.3% (1.4%), and sinusitis 2.7% (1.4%). The adverse reaction profile for adolescent and pediatric patients was comparable to that observed in adult patients with asthma.

The most common adverse reactions >5% incidence and exceeded placebo by ≥1% with SPIRIVA HANDIHALER (placebo) in COPD trials were upper respiratory tract infection 41% (37%), dry mouth 16% (3%), sinusitis 11% (9%), pharyngitis 9% (7%), non‑specific chest pain 7% (5%), urinary tract infection 7% (5%), dyspepsia 6% (5%), and rhinitis 6% (5%). In addition, the most common reported adverse reaction ≥3% incidence and higher than placebo from the 4‑year trial with SPIRIVA HANDIHALER (placebo) not included above were headache 5.7% (4.5%), depression 4.4% (3.3%), insomnia 4.4% (3.0%), and arthralgia 4.2% (3.1%).

SPIRIVA may interact additively with concomitantly used anticholinergic medications. Avoid coadministration with other anticholinergic‑containing drugs.

SPIRIVA capsules should not be swallowed and should only be inhaled through the mouth (oral inhalation) using the HANDIHALER device. The HANDIHALER device should not be used for administering other medications.

Inform patients not to spray SPIRIVA RESPIMAT into the eyes as this may cause blurring of vision and pupil dilation.

Please see full Prescribing Information for SPIRIVA RESPIMAT including Instructions for Use and SPIRIVA HANDIHALER, including Patient Information and Instructions for Use.

INDICATIONS

SPIRIVA RESPIMAT, 1.25 mcg, is a bronchodilator indicated for the long-term, once-daily, maintenance treatment of asthma in patients 6 years of age and older.

SPIRIVA RESPIMAT, 2.5 mcg, and SPIRIVA HANDIHALER are indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, and for reducing COPD exacerbations.

SPIRIVA is not indicated for relief of acute bronchospasm.

Please see full Prescribing Information for SPIRIVA RESPIMAT including Instructions for Use and SPIRIVA HANDIHALER, including Patient Information and Instructions for Use.

CL-SVR-0045 02.15.2017

IMPORTANT SAFETY INFORMATION for SPIRIVA HANDIHALER and SPIRIVA RESPIMAT

SEE MORE

INDICATIONS

SPIRIVA RESPIMAT, 1.25 mcg, is a bronchodilator indicated for the long-term, once-daily, maintenance treatment of asthma in patients 6 years of age and older.

SPIRIVA RESPIMAT, 2.5 mcg, and SPIRIVA HANDIHALER are indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, and for reducing COPD exacerbations.

SPIRIVA is not indicated for relief of acute bronchospasm.

Important Safety Information

SPIRIVA is contraindicated in patients with a history of hypersensitivity to tiotropium, ipratropium, or any component of either product. Immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash have been reported.

SPIRIVA is intended as a once-daily maintenance treatment and should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. In the event of an attack, a rapid-acting beta2‑agonist should be used.

More Important Safety Information

Important Safety Information (continued)

Immediate hypersensitivity reactions, including urticaria, angioedema (swelling of lips, tongue, or throat), rash, bronchospasm, anaphylaxis, or itching may occur after administration of SPIRIVA. If such a reaction occurs, discontinue SPIRIVA at once and consider alternative treatments. Given the similar structural formula of atropine to tiotropium, patients with a history of hypersensitivity reactions to atropine or its derivatives should be closely monitored for similar hypersensitivity reactions to SPIRIVA.

SPIRIVA HANDIHALER should be used with caution in patients with severe hypersensitivity to milk proteins.

Inhaled medicines, including SPIRIVA, may cause paradoxical bronchospasm. If this occurs, it should be treated with an inhaled short‑acting beta2‑agonist, such as albuterol. Treatment with SPIRIVA should be stopped and other treatments considered.

SPIRIVA should be used with caution in patients with narrow‑angle glaucoma. Prescribers and patients should be alert for signs and symptoms of acute narrow‑angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Since dizziness and blurred vision may occur with the use of SPIRIVA, caution patients about engaging in activities such as driving a vehicle, or operating appliances or machinery.

SPIRIVA should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination), 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) and treated with SPIRIVA should be monitored closely for anticholinergic side effects.

The most common adverse reactions >3% incidence and higher than placebo with SPIRIVA RESPIMAT (placebo) in COPD trials were pharyngitis 11.5% (10.1%), cough 5.8% (5.5%), dry mouth 4.1% (1.6%), and sinusitis 3.1% (2.7%).

The most common adverse reactions >2% incidence and higher than placebo with SPIRIVA RESPIMAT (placebo) in asthma trials in adults were pharyngitis 15.9% (12.4%), headache 3.8% (2.7%), bronchitis 3.3% (1.4%), and sinusitis 2.7% (1.4%). The adverse reaction profile for adolescent and pediatric patients was comparable to that observed in adult patients with asthma.

The most common adverse reactions >5% incidence and exceeded placebo by ≥1% with SPIRIVA HANDIHALER (placebo) in COPD trials were upper respiratory tract infection 41% (37%), dry mouth 16% (3%), sinusitis 11% (9%), pharyngitis 9% (7%), non‑specific chest pain 7% (5%), urinary tract infection 7% (5%), dyspepsia 6% (5%), and rhinitis 6% (5%). In addition, the most common reported adverse reaction ≥3% incidence and higher than placebo from the 4‑year trial with SPIRIVA HANDIHALER (placebo) not included above were headache 5.7% (4.5%), depression 4.4% (3.3%), insomnia 4.4% (3.0%), and arthralgia 4.2% (3.1%).

SPIRIVA may interact additively with concomitantly used anticholinergic medications. Avoid coadministration with other anticholinergic‑containing drugs.

SPIRIVA capsules should not be swallowed and should only be inhaled through the mouth (oral inhalation) using the HANDIHALER device. The HANDIHALER device should not be used for administering other medications.

Inform patients not to spray SPIRIVA RESPIMAT into the eyes as this may cause blurring of vision and pupil dilation.

Please see full Prescribing Information for SPIRIVA RESPIMAT including Instructions for Use and SPIRIVA HANDIHALER, including Patient Information and Instructions for Use.

INDICATIONS

SPIRIVA RESPIMAT, 1.25 mcg, is a bronchodilator indicated for the long-term, once-daily, maintenance treatment of asthma in patients 6 years of age and older.

SPIRIVA RESPIMAT, 2.5 mcg, and SPIRIVA HANDIHALER are indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, and for reducing COPD exacerbations.

SPIRIVA is not indicated for relief of acute bronchospasm.

Please see full Prescribing Information for SPIRIVA RESPIMAT including Instructions for Use and SPIRIVA HANDIHALER, including Patient Information and Instructions for Use.

CL-SVR-0045 02.15.2017

References

  1. SPIRIVA RESPIMAT [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2019.
  2. Hamelmann E, Bernstein JA, Vandewalker M, et al. A randomized controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017;49(1):1-10.
  3. Hamelmann E, Bernstein JA, Vandewalker M, et al. A randomized controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017;(suppl):1-8.
  4. Data on File. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2013-2016.
  5. Kerstjens HAM, Casale TB, Bleecker ER, et al. Tiotropium or salmeterol as add-on therapy to inhaled corticosteroids for patients with moderate symptomatic asthma: two replicate, double-blind, placebo-controlled, parallel-group, active-comparator, randomised trials. Lancet Respir Med. 2015;3(5):367-376.
  6. Vogelberg C et al. J Allergy Clin Immunol Pract. 2018;6:2160-2162.e9.
  7. Szefler SJ et al. J Allergy ClinImmunol. 2017;140:1277-1287.