Glycopyrronium Inhaled

Glycopyrronium is a long-acting muscarinic antagonist (LAMA) given by inhalation for maintenance bronchodilation in COPD. Onset is within 5 minutes and the effect lasts 24 hours with once daily dosing in most regions. It is not licensed for asthma.

Classification. Long-acting antimuscarinic bronchodilator, quaternary ammonium compound.

Mechanism. Blocks M3 receptors on airway smooth muscle, reducing cholinergic bronchomotor tone. Dissociation from M3 is slow, which sustains the effect.

Pharmacokinetics. Low lung-to-blood transfer and negligible gut absorption of the swallowed fraction. Terminal half-life after inhalation is long (more than 30 hours), mainly because of slow absorption from the lung. Elimination is predominantly renal, as unchanged drug.

First-line, COPD maintenance. 44 micrograms (equivalent to 50 micrograms of glycopyrronium bromide) once daily by capsule dry powder inhaler. In some regions the labelled dose is 15.6 micrograms twice daily, and a nebulised form of 25 micrograms twice daily exists. Maximum is the labelled daily dose; do not add doses for breakthrough symptoms.

Fixed combinations. Indacaterol with glycopyrronium 85/43 micrograms once daily. Formoterol with glycopyrronium inhaler 9.6/4.8 micrograms, 2 puffs twice daily in regions where it is licensed.

Alternative. Another LAMA or a LAMA with a LABA when symptoms or exacerbations persist.

Emergency. Not used. A short-acting bronchodilator is needed for relief.

Titration and loading. No titration and no loading dose.

Contraindications. Hypersensitivity. Use with caution in narrow-angle glaucoma, bladder outlet obstruction and prostatic enlargement.

Serious adverse effects. Urinary retention, acute angle-closure glaucoma, paradoxical bronchospasm, arrhythmia, hypersensitivity reactions including angioedema.

Common adverse effects. Dry mouth, nasopharyngitis, urinary tract infection, insomnia.

Interactions. Other anticholinergic drugs (including inhaled ipratropium, antihistamines, tricyclic antidepressants and antipsychotics) add antimuscarinic effects.

Common prescribing errors. Swallowing the capsule. Combining two LAMA-containing inhalers. Using it for acute relief.

Special groups.

• Pregnancy and breastfeeding: data are limited; use only if the benefit outweighs risk.

• Older adults: no adjustment, but watch for urinary retention and glaucoma.

• Kidney impairment: exposure rises as GFR falls. In severe impairment (GFR under 30 mL/min) and end-stage disease, use only if benefit outweighs risk and monitor for anticholinergic effects. Liver impairment: no adjustment.

• East Africa: capsule products contain lactose; check availability of the single-agent form, as combinations are more often stocked.

Formulations. Capsule for use only in the matching dry powder device; fixed-dose combination inhalers.

Technique. Place the capsule in the device, pierce, inhale deeply and rapidly, check the capsule is empty and repeat the inhalation if powder remains. Capsules are never swallowed.

Baseline. Spirometry, symptom score, history of glaucoma, urinary symptoms and prostatic disease.

Monitoring. Symptoms, exacerbation count, spirometry at 3 months, inhaler technique at each visit, urinary and eye symptoms.

Stop and reduce rules. Stop for eye pain with visual halos, urinary retention or paradoxical bronchospasm. Therapeutic drug monitoring is not used.

Referral and escalation. Refer to a chest physician when exacerbations persist despite dual long-acting bronchodilator therapy.