Important Safety Information for SPIRIVA RESPIMAT and SPIRIVA HANDIHALER (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.
INDICATIONS FOR SPIRIVA RESPIMAT AND SPIRIVA HANDIHALER
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 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 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.
IMPORTANT SAFETY INFORMATION FOR STIOLTO RESPIMAT (continued)
IMPORTANT SAFETY INFORMATION FOR STIOLTO RESPIMAT
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.
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.
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%).
- 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.
Please see Prescribing Information for STIOLTO RESPIMAT including Boxed WARNING, Medication Guide and Instructions for Use.
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 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.