RxPRODUCT NEWS PROFILE: Spiriva HandiHaler

The Spiriva HandiHaler (tiotropium bromide inhalation powder, Boehringer Ingelheim) reintroduces the role of inhaled anticholinergic medication in chronic obstructive pulmonary disease (COPD) with once-a-day dosing and a unique dose-delivery system. Until now, the only FDAapproved inhaled anticholinergic bronchodilator was ipratropium (Atrovent). It is shorter-acting than tiotropium and is typically dosed 4 times daily.

COPD's progressive, irreversible airway limitation results from 2 changes in the airway tissues: inflammation of the small airways (leading to narrowing), and lung parenchyma destruction (decreasing the lung's elasticity and disrupting alveoli attachment).¹ The fourth-leading cause of death in the United States, COPD results in 500,000 hospitalizations and 14 million office visits annually.² Although 24 million Americans have COPD, only 6 million are being treated.³ Cigarette smoking is the major risk factor, with genetics contributing. Chronic mucus hypersecretion, respiratory infections, and airway reactivity are still being investigated for possible roles.¹ COPD rarely affects patients under age 40. It typically presents with coughing, wheezing, shortness of breath, and increased mucus production.³

Human lung function involves 3 muscarinic receptor subtypes, with a fourth (M4) identified but with unclear function. The parasympathetic ganglia's M1 receptors are responsible for cholinergic neurotransmission. Myocardial and smooth muscle M2 receptors reduce acetylcholine release through negative feedback. M3 receptors constrict the bronchus and stimulate mucus secretion.4 Consequently, antimuscarinic medications, often referred to as anticholinergic, play an important role in the treatment of COPD.

Tiotropium binds to muscarinic receptors. It causes bronchodilation by inhibiting the smooth muscle M3 airway receptors. In vitro and in vivo preclinical studies demonstrated tiotropium's dose-dependent response of >24 hours' duration.⁵

Clinical Trials

Clinical development of once-a-day tiotropium involved 2663 COPD patients in 6 phase-3 studies: two 1-year, placebo-controlled studies; two 6-month, placebo-controlled studies; and two 1-year, ipratropium-controlled studies. The overall results were similar: when compared with those receiving placebo and those receiving ipratropium, patients receiving tiotropium demonstrated improved lung function and decreased use of rescue inhalers, with bronchodilatory effects of tiotropium lasting 24 hours after the dose.⁵

Dry mouth was the most commonly reported side effect. Others were constipation, increased heart rate, blurred vision, glaucoma, urinary difficulty, and urinary retention.⁵

Patient Counseling

Spiriva is available as a powder for inhalation with the HandiHaler system. To use the HandiHaler, the patient should do the following:

• Open the dust cover and mouthpiece
• Place a capsule in the chamber
• Close the mouthpiece until it clicks
• Point the mouthpiece up
• Press and release the piercing button once
• Inhale deeply and exhale
• Place the lips tightly around the mouthpiece
• Breathe deeply enough to make the capsule vibrate

After the lungs are full, the patient should proceed as follows:

• Remove the HandiHaler from the mouth and exhale slowly
• Discard the used capsule
• Close the dust cover for storage

Each 18-mcg tiotropium capsule should remain in the foil package until immediately prior to use.

Pharmacists should counsel that tiotropium is intended for long-term COPD treatment, not for acute bronchospasm. Tiotropium is contraindicated in patients with known atropine or ipratropium sensitivity. It may worsen narrow-angle glaucoma, prostate hyperplasia, or bladder-neck obstruction. Renally excreted, tiotropium requires extra monitoring in patients with creatinine clearance <50 mL/min. Tiotropium is in Pregnancy Category C. Breastfeeding safety has not been determined.⁵

Ms. Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health. Dr. Schott is a pharmacist with Stop and Shop, Wallingford, Conn. Dr. Holmberg is a pharmacist with Phoenix Indian Medical Center, Phoenix, Ariz. The opinions expressed herein are those of the authors and not necessarily of any government agency.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. D. Ryan, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: dryan@mwc.com.