General Information

Spiriva HandiHaler utilizes tiotropium, an antimuscarinic agent, through an inhalation device used to inhale the dry powder contained Spiriva capsules. The capsule is pierced by the device, dispersing tiotropium into the air stream.

The Spiriva HandiHaler is indicated for the treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

The standard gelatin capsule contains 18 mcg of tiotropium. The recommended dosage is the inhalation of the contents of one capsule, once-daily, with the HandiHaler inhalation device.

Clinical Results

FDA approval of Spiriva HandiHaler was based on six phase III trials, enrolling a total of 2,663 subjects over 40, with COPD and a history of smoking greater than 10 pack-years. In addition, subjects had an FEV1 less than or equal to 60 or 65% of predicted, and a ratio of FEV1/FVC of less than or equal to 0.7. The trials consisted of four placebo-controlled studies (one six-month and one one-year) and two ipratropium-controlled studies. Result from these studies showed Spiriva administered once-daily, provided improvement in lung function (forced expiratory volume in one second, FEV1), with peak effect occurring within 3 hours following the first dose.

Results from the one-year, placebo controlled trials showed that the mean improvement in FEV1 at 30 minutes was 0.13 liters (13%) with a peak improvement of 0.24 liters (24%) relative to baseline after the first dose. The mean peak improvement in FEV1, relative to baseline, was 0.28 to 0.31 liters (28% to 31%), after 1 week (day 8) of once-daily treatment. Results from the two six-month, placebo-controlled trials showed improvement in pulmonary function (FEV1) persisted over the spirometric observational period.

Mechanism of Action

Tiotropium is an antimuscarinic agent or anticholinergic with similar affinity to the subtypes of muscarinic receptors, M1 to M5. The drug inhibits M3-receptors at the smooth muscle leading to bronchodilation. The HandiHaler is an inhalation device used to inhale the dry powder contained Spiriva capsules. The capsule is pierced by the device, dispersing tiotropium into the air stream.

Literature References

CCOHTA. Tiotropium: A potential replacement for ipratropium in patients with COPD. Issues in Emerging Health Technologies 2002;35:1-4.

Donohue JF, van Noord JA, Bateman ED et al. A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest 2002;122(1):47-55.

Hvizdos KM, Goa KL. Tiotropium bromide. Drugs; 200262(8):1195-1203.

van Noord JA, Bantje TA, Eland ME et al. A randomized controlled comparison of tiotropium and ipratropium in the treatment. Thorax 2000;55(4):289-94.

Vincken W, van Noord JA, Greefhorst APM et al. Improved health outcomes in patients with COPD during 1 yr=s treatment with tiotropium. Eur Resp J 2002;19(2):209-16.