Tiotropium - Drug Monograph

Introduction

Tiotropium bromide is a long-acting muscarinic antagonist (LAMA) bronchodilator used primarily in the management of chronic obstructive pulmonary disease (COPD). Marketed under brand names including Spiriva, it represents a cornerstone maintenance therapy for airflow obstruction. As an inhaled medication, tiotropium provides sustained bronchodilation with once-daily dosing, significantly improving respiratory symptoms and quality of life for patients with obstructive lung diseases.

Mechanism of Action

Tiotropium competitively and reversibly inhibits muscarinic receptors (M1, M2, and M3 subtypes) in bronchial smooth muscle. The drug's primary therapeutic effect comes from M3 receptor blockade in airway smooth muscle, preventing acetylcholine-induced bronchoconstriction. By antagonizing parasympathetic nervous system activity in the airways, tiotropium reduces bronchial tone and mucus secretion. Its long duration of action results from slow dissociation from muscarinic receptors, particularly the M3 subtype, providing 24-hour bronchodilation with single daily dosing.

Indications

• Maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema
• Reduction of COPD exacerbations
• Not indicated for the relief of acute bronchospasm (rescue medication)

Dosage and Administration

• Tiotropium bromide inhalation powder: 18 mcg once daily via HandiHaler device
• Tiotropium bromide solution: 5 mcg (2 puffs) once daily via Respimat inhaler

• Administer at the same time each day
• For HandiHaler: Place capsule in device, pierce button, inhale deeply and hold breath for 10 seconds
• For Respimat: Prime before first use, administer as two puffs
• Rinse mouth after inhalation to reduce potential anticholinergic effects

• Renal impairment: Use with caution in moderate to severe impairment (CrCl <50 mL/min)
• Hepatic impairment: No dosage adjustment necessary
• Elderly: No dosage adjustment required
• Pediatrics: Not recommended for patients under 18 years

Pharmacokinetics

Contraindications

• Hypersensitivity to tiotropium bromide, atropine, or its derivatives
• Hypersensitivity to milk proteins (for capsule formulation)
• Not indicated for treatment of acute bronchospasm

Warnings and Precautions

• Paradoxical bronchospasm: May occur with inhaled medications; discontinue immediately if occurs
• Cardiovascular effects: Use with caution in patients with cardiac arrhythmias, especially tachycardia
• Narrow-angle glaucoma: May increase intraocular pressure; advise patients to avoid getting powder in eyes
• Urinary retention: Use cautiously in patients with prostatic hyperplasia or bladder-neck obstruction
• Renal impairment: Monitor patients with moderate to severe renal impairment
• Immediate hypersensitivity reactions: May occur; discontinue if angioedema, urticaria, or rash develops

Drug Interactions

• Other anticholinergic agents: Additive anticholinergic effects (e.g., ipratropium, aclidinium)
• β-adrenergic agonists: Additive bronchodilator effects (appropriate combination therapy)
• Drugs prolonging QT interval: Potential additive effect on cardiac repolarization
• Potassium-wasting diuretics: May enhance hypokalemic effects (theoretical concern)

Adverse Effects

• Dry mouth (16%)
• Upper respiratory tract infection (9%)
• Pharyngitis (6%)
• Sinusitis (5%)
• Constipation (4%)
• Dyspepsia (3%)

• Angioedema
• Urinary retention
• Glaucoma
• Tachycardia
• Atrial fibrillation
• Paradoxical bronchospasm

Monitoring Parameters

• Pulmonary function tests (spirometry) at regular intervals
• COPD symptom assessment and exacerbation frequency
• Intraocular pressure in patients with glaucoma risk factors
• Urinary symptoms in elderly males with prostatic hyperplasia
• Renal function in patients with pre-existing renal impairment
• Cardiovascular monitoring in patients with cardiac history

Patient Education

• Proper technique: Demonstrate and observe patient's inhalation technique regularly
• Not for acute symptoms: Emphasize this is not a rescue medication; provide short-acting bronchodilator for acute needs
• Dosing schedule: Take at same time daily; do not exceed recommended dose
• Mouth rinsing: Rinse mouth with water after each dose to reduce dry mouth and systemic absorption
• Device care: Keep dry; do not wash inhalation devices
• Capsule handling: Do not swallow capsules; use only with approved device
• Side effects: Report eye pain, vision changes, difficulty urinating, or persistent dry mouth
• Medical alert: Inform all healthcare providers of tiotropium use

References

1. Global Initiative for Chronic Obstructive Lung Disease. (2023). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2. Tashkin DP, et al. (2008). A 4-year trial of tiotropium in chronic obstructive pulmonary disease. New England Journal of Medicine, 359(15), 1543-1554. 3. Spiriva® (tiotropium bromide) Prescribing Information. FDA-approved labeling. 4. Singh D, et al. (2011). Tiotropium versus salmeterol for the prevention of exacerbations of COPD. New England Journal of Medicine, 364(12), 1093-1103. 5. Celli B, et al. (2010). The effect of pharmacotherapy on rate of decline of lung function in COPD: results from the TORCH study. American Journal of Respiratory and Critical Care Medicine, 178(4), 332-338. 6. Kerwin EM, et al. (2012). Efficacy and safety of once-daily tiotropium Respimat in COPD patients. Respiratory Medicine, 106(4), 583-590.