Tiotropium: uses, appearance and warnings

Tiotropium bromide inhalation powder is indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. Tiotropium bromide inhalation powder is indicated to reduce exacerbations in COPD patients. Tiotropium bromide inhalation powder is an anticholinergic indicated for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), and for reducing COPD exacerbations ( 1 )

Inhalation Powder: Tiotropium bromide inhalation powder consists of tiotropium bromide inhalation powder capsules containing tiotropium powder for oral inhalation and a LupinHaler device. Tiotropium bromide inhalation powder capsules contain 18 mcg of tiotropium (equivalent to 22.5 mcg tiotropium bromide monohydrate USP) in a hypromellose capsule with white opaque cap and white opaque body, imprinted with "LU" on cap and "T18" on body. The LupinHaler device is only intended for use with the tiotropium bromide inhalation powder capsules. Inhalation powder: Tiotropium bromide inhalation powder capsules contain 18 mcg tiotropium powder (equivalent to 22.5 mcg tiotropium bromide monohydrate USP) for use with LupinHaler device ( 3 )

Tiotropium bromide inhalation powder consists of tiotropium bromide inhalation powder capsules and the LupinHaler device. Tiotropium bromide inhalation powder capsules contain 18 mcg of tiotropium (equivalent to 22.5 mcg tiotropium bromide monohydrate USP) in a hypromellose capsule with white opaque cap and white opaque body, imprinted with "LU" on cap and "T18" on body. The LupinHaler device is a white colour inhaler with a green piercing button. It is also imprinted with LupinHaler, Tiotropium Bromide Inhalation Powder and the LUPIN company Logo. It is also imprinted to indicate that Tiotropium Bromide Inhalation Powder Capsules should not be stored in the LupinHaler device and that the LupinHaler device is only to be used with Tiotropium Bromide Inhalation Powder Capsules. Tiotropium bromide inhalation powder capsules are packaged in an aluminum/aluminum blister card and joined along a perforated-cut line. Tiotropium bromide inhalation powder capsules should always be stored in the blister and only removed immediately before use. The drug should be used immediately after the packaging over an individual tiotropium bromide inhalation powder capsule is opened. The following packages are available: carton (NDC 68180-964-12) containing 30 Tiotropium Bromide Inhalation Powder Capsules (3 unit-dose blister cards NDC 68180-964-11) and 1 LupinHaler inhalation device Keep out of reach of children. Do not get powder into eyes. Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. The Tiotropium Bromide Inhalation Powder Capsules should not be exposed to extreme temperature or moisture. Do not store Tiotropium Bromide Inhalation Powder Capsules in the LupinHaler device.

Tiotropium bromide inhalation powder is contraindicated in patients with a hypersensitivity to tiotropium, ipratropium, or any components of this product [see Warnings and Precautions ( 5.2 )] . In clinical trials and postmarketing experience with tiotropium bromide inhalation powder, immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash have been reported [see Warnings and Precautions ( 5.2 )] . Hypersensitivity to tiotropium, ipratropium, or any components of tiotropium bromide inhalation powder capsules ( 4 )

Not for acute use: Not a rescue medication ( 5.1 ) Immediate hypersensitivity reactions: Discontinue tiotropium bromide inhalation powder at once and consider alternatives if immediate hypersensitivity reactions, including angioedema, urticaria, rash, bronchospasm, or anaphylaxis, occur. Use with caution in patients with severe hypersensitivity to milk proteins. ( 5.2 ) Paradoxical bronchospasm: Discontinue tiotropium bromide inhalation powder and consider other treatments if paradoxical bronchospasm occurs ( 5.3 ) Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to consult a physician immediately if this occurs. ( 5.4 ) Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to consult a physician immediately if this occurs. ( 5.5 ) 5.1 Not for Acute Use Tiotropium bromide inhalation powder is intended as a once-daily maintenance treatment for COPD and should not be used for relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. 5.2 Immediate Hypersensitivity Reactions Immediate hypersensitivity reactions, including urticaria, angioedema (including swelling of the lips, tongue, or throat), rash, bronchospasm, anaphylaxis, or itching, may occur after administration of tiotropium bromide inhalation powder. If such a reaction occurs, therapy with tiotropium bromide inhalation powder should be stopped at once and alternative treatments should be considered. 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 tiotropium bromide inhalation powder. In addition, tiotropium bromide inhalation powder should be used with caution in patients with severe hypersensitivity to milk proteins. 5.3 Paradoxical Bronchospasm Inhaled medicines, including tiotropium bromide inhalation powder, may cause paradoxical bronchospasm. If this occurs, it should be treated immediately with an inhaled short- acting beta 2 -agonist such as albuterol. Treatment with tiotropium bromide inhalation powder should be stopped and other treatments considered. 5.4 Worsening of Narrow-Angle Glaucoma Tiotropium bromide inhalation powder 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. 5.5 Worsening of Urinary Retention Tiotropium bromide inhalation powder 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. 5.6 Renal Impairment As a predominantly renally excreted drug, patients with moderate to severe renal impairment (creatinine clearance of <60 mL/min) treated with tiotropium bromide inhalation powder should be monitored closely for anticholinergic side effects [see Clinical Pharmacology ( 12.3 )].

The following adverse reactions are described, or described in greater detail, in other sections: Immediate hypersensitivity reactions [see Warnings and Precautions ( 5.2 )] Paradoxical bronchospasm [see Warnings and Precautions ( 5.3 )] Worsening of narrow-angle glaucoma [see Warnings and Precautions ( 5.4 )] Worsening of urinary retention [see Warnings and Precautions ( 5.5 )] The most common adverse reactions (>5% incidence in the 1-year placebo- controlled trials) were upper respiratory tract infection, dry mouth, sinusitis, pharyngitis, non-specific chest pain, urinary tract infection, dyspepsia, and rhinitis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . …

Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of tiotropium bromide inhalation powder with other anticholinergic-containing drugs. ( 7.2 ) 7.1 Sympathomimetics, Methylxanthines, Steroids Tiotropium bromide inhalation powder has been used concomitantly with short-acting and long-acting sympathomimetic (beta-agonists) bronchodilators, methylxanthines, and oral and inhaled steroids without increases in adverse reactions. 7.2 Anticholinergics There is potential for an additive interaction with concomitantly used anticholinergic medications. Therefore, avoid coadministration of tiotropium bromide inhalation powder with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects [see Warnings and Precautions ( 5.4 , 5.5 ) and Adverse Reactions ( 6 )].