Spiriva (tiotropium) is a new anticholinergic inhalation product approved solely for the treatment of chronic obstructive pulmonary disease (COPD). Its efficacy is only marginally better than that of ipratropium (Atrovent). Unlike Atrovent, Spiriva is only administered once daily. Treatment with Spiriva, as with all other drugs for the treatment of COPD, is symptomatic treatment only, and its clinical efficacy is often not very high. As is the case with so many other illnesses, cessation of smoking is the most efficacious treatment.
Spiriva (tiotropium) is a new anticholinergic product marketed in Denmark since 24 June 2002. Spiriva is indicated solely for the maintenance of COPD. Administration is once a day; Atrovent is taken four times daily. Spiriva is marketed as an inhalation powder only.
The only efficacious therapy for COPD is if the patient stops smoking, so medical treatment of COPD is symptomatic only. Possible therapy choices are short- and long-acting B2 agonists, theophyllin and anticholinergics, alone or in combination with a B2 agonist. Prophylactic treatment with inhalation steroids can be used for patients with severely reduced pulmonary function (FEV1<1.4), although efficacy is also limited in this case.
The efficacy of tiotropium has been compared with that of ipratropium in two studies and salmeterol in two other studies, but there has been no comparison with the combination of ipratropium and B2 agonist that is more commonly used.
In two one-year studies of a total of 535 patients with COPD (FEV1<65%, FVC<70% and not in continuous oxygen therapy), tiotropium 18 g once daily was compared with ipratropium 40 ug four times daily. Tiotropium demonstrated a statistically significantly, albeit clinically relatively slightly, greater efficacy in both pulmonary function (respective differences in trough FEV1 and FVC were 150 and 210 ml after one year) and health-related efficacy endpoints (dyspnoea index, number of exacerbations and SGRQ total score). The NNT for the difference in number of patients with one or more exacerbations was roughly nine, but there was no difference in the number of patients that needed prednisolone. The difference in SF-36 score was significantly better in two out of a total of ten domains. Use of rescue medicine in the tiotropium group was marginally lower – but, again, the difference was statistically significant: about four puffs less per week (for ipratropium 1.7-2.6 and for tiotropium 1.3-2.3 per day). There was no difference in number of patients hospitalised due to exacerbations within one year (7.3% of the tiotropium group versus 11.3 % of the ipratropium group).
In a six-month study of 623 patients with COPD (FEV1<60%, FVC<70% and not in continuous oxygen therapy), 18 ug tiotropium was compared with salmeterol 50 ug twice daily. Again, a slightly better efficacy was observed with tiotropium, i.e. a difference in trough FEV1 of 52 ml after six months. As regards the health-related efficacy endpoints, the number of patients who obtained a clinically relevant SGRQ score was significantly larger in the tiotropium group (51% of the tiotropium group versus 40% and 42% respectively in the salmeterol and placebo groups); there was, however, no difference in SGRQ scores.
Also the second study, in which tiotropium was compared with salmeterol, revealed a significant effect on peak and average FEV1, but – unlike in the first study – there was no significant influence on trough FEV1.
Adverse drug reactions
In the above-mentioned studies, the incidence of dry mouth was significantly higher for tiotropium (12.1%) than for ipratropium (6.1%), but this did not result in more drop-outs.
As is also the case with other anticholinergic products, caution is advised with patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction.
There is no known and presumably little probability of interactions because administration is local. However, Spiriva may not be used together with other anticholinergics.
Cost and cost effectiveness
Spiriva is about 1.7 times more expensive than Atrovent capsules and 4.4 times more expensive than Atrovent spray. However, a pharmacoeconomic analysis has shown that Spiriva is more cost-effective than Atrovent, also when the difference between the prices of the two Atrovent formulations is taken into account. In other words, it is worth paying the higher price for the added efficacy.
Spiriva costs 30% more than salmeterol, but there is no difference in cost-effectiveness. In this respect, it makes no difference which of these two products is prescribed.
||Cost per day (DKK)|
||capsules 40 µg
spray 20 µg/dose
|1 x 4
2 x 4
||ipratropium + fenoterol
|1 x 4
2 x 4
||ipratropium + salbutamol
||2 x 4
||discus 50 µg/dose
spray 25 µg/dose
|1 x 2
2 x 2
||capsules 18 µg
||1 x 1
Prices as at 24 June 2002.
Additional information can be found in the summary of product characteristics published by the Danish Medicines Agency (Danish only).
Last modified: June 24th 2002