Ultra Long Acting Beta 2 Agonists

Ultra long acting beta 2 agonists (indacaterol, olodaterol and vilanterol) give 24 hour bronchodilation from one daily dose. Indacaterol and olodaterol are used in COPD, and vilanterol is given in fixed combination with an inhaled corticosteroid or a long acting antimuscarinic.

Mechanism. High intrinsic activity at the beta 2 receptor and lipophilic membrane retention give a prolonged effect with rapid onset.

Pharmacokinetics. Steady state is reached in 12 to 15 days for indacaterol. Vilanterol is a CYP3A4 substrate, and strong inhibitors raise exposure. Indacaterol and olodaterol have low systemic exposure at labelled doses.

Indacaterol. 150 mcg once daily by dry powder capsule, with a higher strength of 300 mcg in some regions. COPD only.

Olodaterol. 5 mcg once daily, given as 2 puffs of 2.5 mcg by soft mist inhaler. COPD only.

Vilanterol. 22 mcg delivered dose once daily, only in fixed combination. With fluticasone furoate it is 92/22 mcg for COPD and 92/22 or 184/22 mcg for asthma. With umeclidinium it is 55/22 mcg once daily.

Other combinations. Indacaterol with glycopyrronium, 85/43 mcg delivered dose once daily. Olodaterol with tiotropium, 5/5 mcg once daily.

Differences. Onset is quickest with indacaterol and olodaterol, and slower with vilanterol. Indacaterol causes post-inhalation cough in a minority of patients.

COPD. Used when persistent breathlessness remains on a short acting bronchodilator. Once daily dosing helps adherence. Combination with a long acting antimuscarinic is preferred when breathlessness persists, and an inhaled corticosteroid is added only when exacerbations continue with eosinophils of 300 cells/microlitre or more.

Asthma. Vilanterol is used only in fixed combination with an inhaled corticosteroid. Indacaterol and olodaterol are not for asthma.

Not for acute relief. A short acting agent is always kept for rescue.

Region. Cost and supply may limit use; confirm local availability before planning long term therapy.

Adverse effects. Cough after inhalation (indacaterol), tremor, palpitations, tachycardia, hypokalaemia, hyperglycaemia, QT prolongation. Paradoxical bronchospasm needs the product stopped.

Cautions. Ischaemic heart disease, arrhythmia, thyrotoxicosis, diabetes, uncontrolled hypertension, hypokalaemia.

Interactions. Non-selective beta blockers are contraindicated in asthma and best avoided in bronchospastic disease. Strong CYP3A4 inhibitors raise vilanterol exposure. Additive hypokalaemia with diuretics, corticosteroids and theophylline. QT prolonging drugs add risk.

Monitoring. Breathlessness and exacerbation count, spirometry, heart rate, potassium in at-risk patients, and inhaler technique with the single dose device.

Special groups. Pregnancy: limited data, used only if needed. Breastfeeding: use with caution. Older adults: no adjustment, watch for tachyarrhythmia. Hepatic impairment: severe impairment lacks data, so use with caution. Renal impairment: no adjustment.

Referral and escalation. Two or more moderate exacerbations or one admission in a year on dual bronchodilator therapy needs specialist review and consideration of an inhaled corticosteroid.