Tiotropium

• COPD Maintenance
• Chronic Bronchitis
• Emphysema
• Asthma Maintenance

Tiotropium is a long-acting muscarinic antagonist (LAMA) used for maintenance treatment of COPD and asthma. It provides sustained bronchodilation for 24 hours with once-daily dosing.

Mechanism of Action

Tiotropium works through anticholinergic mechanisms:

• Muscarinic receptor antagonism: Blocks M1, M2, and M3 receptors
• Prolonged M3 binding: Very slow dissociation from M3 receptors (>35 hours)
• Bronchodilation: M3 blockade in airway smooth muscle causes relaxation
• Reduced mucus secretion: M3 inhibition decreases goblet cell activity
• 24-hour duration: Long receptor binding enables once-daily dosing

The kinetic selectivity for M3 over M2 receptors results in sustained bronchodilation without significant cardiac effects.

Available Formulations

• Spiriva HandiHaler: Tiotropium bromide powder 18 mcg capsules for inhalation
• Spiriva Respimat: Tiotropium bromide solution 1.25 mcg/actuation and 2.5 mcg/actuation (soft mist inhaler)

Medical Uses

FDA-Approved Indications:

• Long-term, once-daily maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema
• Long-term, once-daily maintenance treatment of asthma in patients ≥6 years (Spiriva Respimat)
• Reduction of COPD exacerbations

Dosing Guidelines

COPD (Adults):

• HandiHaler: One 18 mcg capsule inhaled once daily via HandiHaler device
• Respimat: Two inhalations of 2.5 mcg (5 mcg total) once daily

Asthma (Adults and children ≥6 years):

• Respimat: Two inhalations of 1.25 mcg (2.5 mcg total) once daily

Administration:

• Inhale at same time each day
• HandiHaler capsules are for inhalation only; do not swallow
• Prime Respimat before first use

Important Safety Information

Contraindications:

• Known hypersensitivity to tiotropium, ipratropium, or atropine derivatives
• History of hypersensitivity to any component (including milk protein for HandiHaler)

Warnings and Precautions:

• Not for acute episodes: Not a rescue medication
• Paradoxical bronchospasm: May occur; discontinue and use alternative therapy
• Urinary retention: Use with caution in patients with narrow-angle glaucoma or urinary retention
• Narrow-angle glaucoma: May worsen; avoid getting product in eyes
• Renal impairment: Use with caution in severe impairment

Drug Interactions

• Other anticholinergics (ipratropium): Avoid concurrent use; additive anticholinergic effects
• Other inhaled medications: Generally compatible; coordinate with other controller medications

Special Populations

• Hepatic Impairment: No adjustment needed (minimal hepatic metabolism)
• Renal Impairment: Use with caution in moderate to severe impairment (CrCl ≤50 mL/min); monitor for anticholinergic side effects
• Elderly: No specific adjustment; more susceptible to anticholinergic effects
• Pregnancy: Limited data; use only if benefit outweighs risk
• Lactation: Unknown if excreted in milk
• Pediatric: Respimat approved for asthma in children ≥6 years