Ipratropium bromide

Budesonide

Ipratropium bromide (42 micrograms per nostril bd) has been compared with budesonide (84 micrograms per nostril bd) for 6 months in a randomized, double-blind trial in 146 children with perennial rhinitis [ ]. Both treatments resulted in significant improvements in rhinorrhea, sneezing, and congestion (as rated by both patients and physicians) and improved quality of life. Budesonide achieved better control of sneezing than ipratropium throughout the study period and better control of congestion than ipratropium in the later part of the study. Of 36 patients who did not complete the study, largely for administrative reasons, six using ipratropium withdrew owing to lack of efficacy. There were no reports of systemic anticholinergic adverse effects. The commonest nasal adverse events in both groups were nasal congestion (23% with ipratropium and 18% with budesonide) and rhinitis (13% with ipratropium and 7% with budesonide). Of nasal adverse events considered to be related to treatment, epistaxis and nasal irritation were more common with budesonide (10% and 4% respectively) than with ipratropium (8 and 0%). Sneezing occurred in 5% of those using ipratropium and in none of those using budesonide, probably reflecting the better efficacy of budesonide for control of sneezing. Overall both drugs were well tolerated.

Ipratropium (42 micrograms per nostril tds), budesonide (84 micrograms per nostril bd), and ipratropium + budesonide for 2 weeks have been studied in a randomized, double-blind, placebo-controlled trial in 533 patients with perennial rhinitis [ ]. As monotherapy, both ipratropium and budesonide produced significant reductions in rhinorrhea compared with placebo, and budesonide was more effective than ipratropium in reducing congestion and sneezing. Non-nasal adverse events occurred equally in all three groups. The incidences of epistaxis, nasal congestion, and nasal irritation were similar in all three groups (1–5%) but there was a greater incidence of nasal dryness (3% versus less than 1%) and blood-tinged mucus (4% versus 2%) with ipratropium. Combination therapy with ipratropium and budesonide reduced the severity and duration of rhinorrhea in 74% and 66% of patients compared with 57% and 50% for ipratropium, 64% and 54% for budesonide, and 47% and 38% for placebo. There were no other advantages for combination therapy over budesonide. Nasal adverse events occurred in all groups, including placebo, but patients who had two weeks of budesonide in the monotherapy arm of the study followed by combination therapy had more epistaxis (5%) and more nasal dryness (5%) than patients who had ipratropium before combination treatment. The authors concluded that combination therapy is superior to monotherapy, with no increase in adverse reactions. However, the effect of combination therapy over monotherapy in this study is quite small and does not appear to have reached statistical significance. Nevertheless, most adverse effects seem to have been related to budesonide rather than to ipratropium. The addition of ipratropium in a patient already taking budesonide seems to be safe and may increase efficacy.

Salmeterol

A double-blind, double-dummy, parallel-group study in 144 patients with severe COPD (FEV ₁ 41% of predicted) has been conducted over 12 weeks to determine whether the combination of salmeterol 50 micrograms bd + ipratropium 40 micrograms bd was better than salmeterol alone [ ]. At the beginning of treatment salmeterol increased FEV ₁ (at peak 7% of predicted) for over 12 hours. Salmeterol + ipratropium produced a greater bronchodilator response (at peak 11% of predicted) than salmeterol alone during the first 6 hours after inhalation. There were significant improvements in daytime symptom scores and peak flows with both salmeterol and salmeterol + ipratropium compared with placebo. Adverse events were similar in the treatment groups; headache (six patients with salmeterol + ipratropium, four with salmeterol, and 11 with placebo) and cough were the most common drug-related adverse events. Over the 12 weeks, 35 patients had an exacerbation of COPD, 36% with placebo, 23% with salmeterol, and 13% with salmeterol + ipratropium.