Introduction
Spiriva (tiotropium bromide) is a long-acting muscarinic antagonist (LAMA) bronchodilator used primarily for the maintenance treatment of chronic obstructive pulmonary disease (COPD). It was first approved by the FDA in 2004 and has become a cornerstone therapy in COPD management. Spiriva is available as both a dry powder inhaler (Spiriva HandiHaler) and a soft mist inhaler (Spiriva Respimat).
Mechanism of Action
Tiotropium bromide is an anticholinergic agent that competitively inhibits muscarinic receptors (primarily M1, M2, and M3 subtypes) in bronchial smooth muscle. By blocking acetylcholine at these receptors, it prevents bronchoconstriction and reduces mucus secretion. The drug demonstrates kinetic selectivity for M1 and M3 receptors over M2 receptors, resulting in prolonged bronchodilation. Its effects persist for at least 24 hours, allowing for once-daily dosing.
Indications
- Maintenance treatment of bronchospasm associated with COPD, including chronic bronchitis and emphysema
- Reduction of COPD exacerbations
- Not indicated for the relief of acute bronchospasm
Dosage and Administration
Spiriva HandiHaler:- 18 mcg capsule inhaled once daily via HandiHaler device
- 2.5 mcg per actuation (5 mcg total dose) once daily
- Should be administered at the same time each day
- Not for use as a rescue medication
- Renal impairment: Use with caution in patients with moderate to severe renal impairment (CrCl < 50 mL/min)
- Hepatic impairment: No dosage adjustment necessary
- Geriatric patients: No dosage adjustment required
Pharmacokinetics
Absorption: Minimal systemic absorption following inhalation (approximately 19.5% of administered dose) Distribution: Plasma protein binding: 72%; Volume of distribution: 32 L/kg Metabolism: Extensively metabolized by cytochrome P450-mediated oxidation followed by glutathione conjugation Elimination: Half-life: 5-6 days; primarily eliminated unchanged in feces (74%); renal excretion (14%) Onset of action: Significant bronchodilation within 30 minutes Peak effect: 3 hours post-inhalation Duration: >24 hoursContraindications
- Hypersensitivity to tiotropium bromide, ipratropium bromide, or any component of the formulation
- Patients with a history of hypersensitivity reactions to atropine or its derivatives
Warnings and Precautions
Paradoxical Bronchospasm: Can occur with inhalation; discontinue immediately if experienced Cardiovascular Effects: May increase heart rate and cause palpitations; use with caution in patients with cardiac disorders Narrow-Angle Glaucoma: May precipitate acute angle-closure glaucoma; advise patients to avoid contact with eyes Urinary Retention: Use with caution in patients with bladder outlet obstruction or prostatic hyperplasia Renal Impairment: Use with caution in patients with moderate to severe renal impairment Hypersensitivity Reactions: Immediate hypersensitivity reactions, including angioedema, may occurDrug Interactions
Anticholinergic Agents: Concurrent use may potentiate adverse effects (e.g., dry mouth, constipation, urinary retention) β-adrenergic Agonists: Additive bronchodilator effects; may be used concomitantly Corticosteroids: No significant interactions reported Diuretics: Potential additive hypokalemic effects when used with other hypokalemia-inducing drugs CYP450 Interactions: Unlikely to be clinically significant due to minimal systemic absorptionAdverse Effects
Common (≥1%):- Dry mouth (16%)
- Upper respiratory tract infection (9%)
- Sinusitis (5%)
- Pharyngitis (4%)
- Constipation (3%)
- Dyspepsia (3%)
- Angioedema and hypersensitivity reactions
- Paradoxical bronchospasm
- Worsening of narrow-angle glaucoma
- Worsening of urinary retention
- Cardiovascular events (tachycardia, palpitations)
- Renal calculi
Monitoring Parameters
- Pulmonary function tests (FEV1, peak flow)
- COPD symptom control and exacerbation frequency
- Cardiovascular status (heart rate, blood pressure)
- Ocular symptoms (especially in patients with glaucoma risk factors)
- Urinary symptoms in patients with prostatic hyperplasia
- Renal function in patients with pre-existing renal impairment
- Signs of hypersensitivity reactions
Patient Education
- Use regularly as prescribed, not for acute symptom relief
- Administer at the same time each day
- Keep rescue inhaler available for acute symptoms
- Rinse mouth after inhalation to reduce dry mouth and prevent oral candidiasis
- Avoid getting powder in eyes (may cause blurring of vision or eye pain)
- Report immediately: eye pain, vision changes, difficulty urinating, swelling of lips/tongue/throat
- Do not exceed recommended dosage
- Proper inhaler technique is essential for effectiveness
- Regular follow-up with healthcare provider is important
References
1. FDA Prescribing Information: Spiriva (tiotropium bromide). 2020 2. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2023 3. Tashkin DP, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543-1554 4. Vincken W, et al. Improved health outcomes in patients with COPD during 1 year's treatment with tiotropium. Eur Respir J. 2002;19(2):209-216 5. Celli B, et al. The effect of pharmacotherapy on rate of decline of lung function in COPD: results from the TORCH study. Am J Respir Crit Care Med. 2008;178(4):332-338 6. American Thoracic Society/European Respiratory Society standards for the diagnosis and management of patients with COPD. 2022