Allen & Hanburys Ltd

Potentially serious hypokalaemia may result from ß₂ agonist therapy.  Particular caution is advised in acute severe asthma as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics.

Co-administration of ketoconazole (400 mg orally once daily) and salmeterol (50 mcg inhaled twice daily) in 15 healthy subjects for 7 days resulted in a significant increase in plasma salmeterol exposure (1.4-fold Cmax and 15-fold AUC).  This may lead to an increase in the incidence of other systemic effects of salmeterol treatment (e.g. prolongation of QTc interval and palpitations) compared with salmeterol or ketoconazole treatment alone (see Section 4.4).

Clinically significant effects were not seen on blood pressure, heart rate, blood glucose and blood potassium levels.  Co-administration with ketoconazole did not increase the elimination half-life of salmeterol or increase salmeterol accumulation with repeat dosing.

The concomitant administration of ketoconazole should be avoided, unless the benefits outweigh the potentially increased risk of systemic side effects of salmeterol treatment.  There is likely to be a similar risk of interaction with other potent CYP3A4 inhibitors (e.g. itraconazole, telithromycin, ritonavir).

Co-administration of erythromycin (500mg orally three times a day) and salmeterol (50µg inhaled twice daily) in 15 healthy subjects for 6 days resulted in a small but non-statistically significant increase in salmeterol exposure (1.4-fold Cmax and 1.2-fold AUC).  Co-administration with erythromycin was not associated with any serious adverse effects.