Salmeterol

Salmeterol is a long-acting beta-2 agonist (LABA) with slow onset (10 to 20 minutes) and 12-hour duration. It is used for maintenance bronchodilation in asthma, only together with an inhaled corticosteroid, and in COPD. It is never a reliever.

Classification. Long-acting beta-2 agonist.

Mechanism. Highly lipophilic; remains in the cell membrane near the beta-2 receptor, producing prolonged receptor stimulation and bronchodilation.

Pharmacokinetics. Minimal systemic absorption from the lung. Hepatic metabolism by CYP3A4. Elimination mainly in faeces.

First-line, asthma (always with an inhaled corticosteroid). Inhaler 50 micrograms (2 puffs of 25 micrograms) twice daily, or dry powder 50 micrograms twice daily. Maximum 100 micrograms twice daily in severe disease under specialist direction.

First-line, COPD. 50 micrograms twice daily by dry powder, or 50 micrograms (2 puffs) twice daily by inhaler.

Fixed combination with fluticasone propionate. Dry powder 50/100, 50/250 or 50/500 micrograms one inhalation twice daily, or inhaler 25/50, 25/125 or 25/250 micrograms two puffs twice daily. Choose the corticosteroid strength by asthma severity.

Children. From 4 years, 50 micrograms twice daily with an inhaled corticosteroid.

Titration. Step up the inhaled corticosteroid before raising the LABA dose. Step down if control holds for 3 months. No loading dose.

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

Boxed-warning-level risk. Used alone in asthma, LABAs raise the risk of asthma-related death. Never prescribe salmeterol as asthma monotherapy.

Contraindications. Hypersensitivity; acute attacks; monotherapy in asthma. Strong CYP3A4 inhibitors should be avoided.

Serious adverse effects. Arrhythmia, QT prolongation, hypokalaemia, paradoxical bronchospasm, pneumonia risk with the combination in COPD.

Common adverse effects. Tremor, palpitations, headache, cramps.

Interactions. Ritonavir, ketoconazole, itraconazole and clarithromycin raise salmeterol exposure and arrhythmia risk. Non-selective beta-blockers antagonise the effect. Hypokalaemic drugs add risk.

Common prescribing errors. Prescribing as relief. Prescribing without an inhaled corticosteroid in asthma. Combining with ritonavir-boosted regimens.

Special groups.

• Pregnancy: use only when benefit outweighs risk. Breastfeeding: no firm data, probably acceptable.

• Older adults: monitor heart rhythm and potassium.

• Kidney impairment: no adjustment. Liver impairment: exposure increases in severe impairment; use with caution.

• East Africa: many people take ritonavir-boosted antiretroviral regimens, which makes the CYP3A4 interaction relevant here.

Formulations. Inhaler 25 micrograms/actuation; dry powder 50 micrograms/dose; fixed combinations with fluticasone propionate as listed in the dosing section.

Technique. Rinse the mouth after combination inhalers. Dry powder devices are used without a spacer; inhale rapidly and deeply.

Baseline. Spirometry, heart rate, potassium if other risk factors.

Monitoring. Symptom control, reliever use, exacerbations, spirometry at 3 to 6 months, heart rate.

Stop and reduce rules. Step down when control is sustained. Stop if arrhythmia or paradoxical bronchospasm. Therapeutic drug monitoring is not used.

Referral and escalation. Refer to a specialist if control fails at the highest doses of corticosteroid with a LABA.