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.

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.

Side Effects

Adverse events associated with the use of Spiriva may include (but are not limited to) the following:

• dry mouth
• arthritis
• coughing
• influenza-like symptoms
• sinusitis

Dosing/Administration

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 Trial Results

FDA approval of Spiriva HandiHaler was based on six phase 3 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 percent 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 three 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 percent) with a peak improvement of 0.24 liters (24 percent) relative to baseline after the first dose. The mean peak improvement in FEV1, relative to baseline, was 0.28 to 0.31 liters (28 percent to 31 percent) after one 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.