Titan

Approved Indications:

• Chronic Obstructive Pulmonary Disease (COPD):
• Maintenance treatment of bronchospasm associated with COPD
• Reduction of COPD exacerbations
• Asthma:
• Long-term maintenance treatment of asthma in adults and children ≥6 years inadequately controlled with inhaled corticosteroids and long-acting beta agonists

Clinically Accepted Off-label Uses:

• Bronchiectasis (as adjunct therapy)
• Persistent airflow limitation in smokers without full COPD diagnosis (select cases)

Formulations:

• Tiotropium bromide inhalation powder (Spiriva HandiHaler)
• Tiotropium bromide inhalation spray (Spiriva Respimat)

Adults with COPD:

• HandiHaler: 18 mcg (one capsule) inhaled once daily via HandiHaler device
• Respimat: 5 mcg (2 inhalations of 2.5 mcg) once daily

Adults with Asthma:

• Respimat: 2.5 mcg (2 inhalations of 1.25 mcg) once daily

Pediatric Asthma (≥6 years):

• Respimat: 2 inhalations of 1.25 mcg (total 2.5 mcg) once daily

Elderly:

• No dosage adjustment required

Renal Impairment:

• Use with caution in moderate-to-severe impairment; monitor for anticholinergic effects

Hepatic Impairment:

• No dose adjustment necessary

Administration Notes:

• Should be taken at the same time every day
• Not for acute bronchospasm or rescue use
• Do not swallow capsules (HandiHaler); they are for inhalation only

Tiotropium is a long-acting muscarinic antagonist (LAMA) that competitively and reversibly inhibits M3 muscarinic receptors on airway smooth muscle. This blockade prevents acetylcholine-induced bronchoconstriction, leading to prolonged airway dilation. Its high receptor affinity and slow dissociation provide 24-hour bronchodilation, improving airflow and reducing exacerbation risk in COPD and asthma patients.

• Absorption: Rapid absorption via lungs; oral bioavailability is low (<3%)
• Distribution: Moderate plasma protein binding (~72%); steady-state volume of distribution ~32 L/kg
• Metabolism: Partially metabolized by liver via CYP2D6 and CYP3A4; primarily undergoes non-enzymatic ester cleavage
• Excretion: Primarily excreted unchanged via urine (~74%); minor fecal excretion
• Half-life: Terminal elimination half-life ~5–6 days (Respimat), ~35 hours (HandiHaler)
• Onset of Action: Within 30 minutes
• Peak Plasma Concentration: Reached in 5–7 minutes (inhalation)

• Pregnancy: No FDA pregnancy category (previously Category C). Use only if clearly needed; animal studies show adverse fetal effects at high doses.
• Lactation: Unknown if excreted into human milk. Caution is advised. Monitor infant for anticholinergic side effects (e.g., dry mouth, constipation).
• General Advice: Use during pregnancy and lactation only if benefits outweigh potential risks.

• Primary Class: Long-Acting Muscarinic Antagonist (LAMA)
• Subclass: Anticholinergic bronchodilator
• Generation: Long-acting inhaled agent

• Hypersensitivity to tiotropium, atropine, or its derivatives
• Hypersensitivity to any component of the formulation, including lactose (HandiHaler)

• Not for Acute Use: Do not use for initial treatment of acute bronchospasm
• Paradoxical Bronchospasm: May occur; discontinue immediately if it does
• Narrow-Angle Glaucoma: Use with caution; may worsen condition
• Urinary Retention: Monitor in patients with prostatic hyperplasia or bladder neck obstruction
• Renal Impairment: Increased systemic exposure; monitor for anticholinergic side effects
• Hypersensitivity Reactions: Rare cases of angioedema, urticaria, rash
• Eye Contact: May cause pupil dilation and blurred vision if sprayed into eyes

Common:

• Respiratory: Dry mouth, cough, sore throat, sinusitis
• Gastrointestinal: Constipation, nausea
• Neurological: Headache, dizziness

Less Common/Serious:

• Urinary: Urinary retention, dysuria
• Ocular: Blurred vision, increased intraocular pressure
• Hypersensitivity: Rash, angioedema, anaphylaxis (rare)

Rare:

• Atrial fibrillation, palpitations
• Glaucoma exacerbation

• Anticholinergic Agents: Additive effects; avoid concomitant use
• CYP2D6 & CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin): May increase systemic exposure, though clinical significance is minimal
• No significant food or alcohol interactions
• Enzyme Systems Involved: CYP2D6, CYP3A4 (minor pathway)

• GINA (Global Initiative for Asthma) guidelines now include tiotropium as an option for step-up therapy in severe asthma for patients ≥6 years not controlled with ICS-LABA
• GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2024 update reinforces LAMA use as first-line for persistent COPD symptoms or frequent exacerbations

• Inhalation Powder (HandiHaler):
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and heat
• Do not store capsules in the inhaler
• Inhalation Spray (Respimat):
• Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F)
• After cartridge insertion, use within 3 months
• Do not freeze