Tiotropium

Tiotropium is a once daily long acting antimuscarinic inhaled for the maintenance of chronic obstructive pulmonary disease and as add on therapy in poorly controlled asthma. It is not for relief of acute symptoms. It is a quaternary ammonium compound with minimal systemic absorption.

Classification. Long acting muscarinic antagonist.

Mechanism. Binds M1 to M3 receptors and dissociates very slowly from M3 receptors on airway smooth muscle, giving 24 hour bronchodilation. Dissociation from M2 receptors is faster, which preserves some autoreceptor function.

Pharmacodynamics. Onset within 30 minutes; peak 3 hours; duration 24 hours or more. Reduces exacerbations, improves FEV1 and lung hyperinflation in chronic obstructive pulmonary disease.

Pharmacokinetics. Lung deposition about 20 to 25%; swallowed fraction poorly absorbed. Terminal half life after inhalation is long, about 5 to 6 days, with steady state in 2 to 3 weeks. About 70% of absorbed drug is excreted unchanged in urine.

Chronic obstructive pulmonary disease, adult.

• Dry powder capsule 18 micrograms, one capsule inhaled once daily through the matching device.

• Soft mist inhaler 5 micrograms (two actuations of 2.5 micrograms) once daily.

• No loading dose or titration; maximum one dose in 24 hours.

• Continue long term; add a long acting beta agonist if symptoms persist.

Add on in asthma (persistent symptoms despite inhaled corticosteroid and long acting beta agonist), adult. Soft mist inhaler 5 micrograms (two actuations of 2.5 micrograms) once daily in most markets; some markets use a 1.25 microgram actuation product, giving 2.5 micrograms daily. Use under specialist direction in children from 6 years.

Bronchiectasis and other uses. Not established.

Contraindications. Hypersensitivity to tiotropium, atropine or its derivatives. The dry powder capsule contains lactose with milk protein; avoid in severe milk protein allergy.

Warnings. Paradoxical bronchospasm. Worsening angle closure glaucoma, bladder outflow obstruction and prostatic hypertrophy. Not for acute attacks. Capsules must never be swallowed (they are for inhalation only).

Adverse effects. Dry mouth (most common), constipation, cough, pharyngitis, sinusitis, urinary retention, tachycardia, blurred vision, dizziness.

Interactions. Avoid other long acting or regular short acting antimuscarinics (including ipratropium) because effects add. Combination with long acting beta agonists is intended.

Special groups.

• Pregnancy: avoid unless benefit is clear; limited data.

• Breastfeeding: limited data; likely small exposure; use if needed.

• Older adults: watch for urinary retention and dry mouth.

• Kidney impairment: eGFR 60 mL/min or under (moderate to severe): exposure rises; use with close monitoring for antimuscarinic effects. Dose unchanged.

• Liver impairment: no adjustment.

Formulations. Dry powder capsules 18 micrograms for a capsule inhaler; soft mist inhaler cartridges delivering 2.5 micrograms a puff.

Technique. Inhale at the same time each day. Capsule inhaler: pierce and inhale twice from the same capsule to empty it. Soft mist inhaler: prime before first use, two puffs each dose. Rinse the mouth if dry mouth or oral irritation occurs.

Baseline. Spirometry, exacerbation history, eye pressure and prostate symptoms where relevant.

Monitoring. Symptoms, exacerbation rate, FEV1 at 4 to 12 weeks, inhaler technique, antimuscarinic adverse effects.

Stopping. Stop if there is no symptomatic or exacerbation benefit after a reasonable period (about 3 months) or if glaucoma or retention develops.

Common prescribing errors. Swallowing the capsule; using it for rescue; combining it with regular ipratropium; omitting spacing from other inhaled drugs.