General Information

Atrovent HFA is an anticholinergic and works by inhibiting the transmission of parasympathetic nerve impulses, thereby reducing spasms of smooth muscles.

Atrovent HFA is specifically indicated for the maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

Atrovent HFA is supplied as an inhalation aerosol. The usual starting dose is two inhalations four times a day. Patients may take additional inhalations as required; however, the total number of inhalations should not exceed 12 in 24 hours. Each inhaler provides sufficient medication for 200 actuations. The inhaler should be discarded after the labeled number of actuations has been used. The amount of medication in each actuation cannot be assured after this point, even though the canister is not completely empty.

Mechanism of Action

Atrovent HFA is an anticholinergic (parasympatholytic) agent which appears to inhibit vagally-mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released at the neuromuscular junctions in the lung. Anticholinergics prevent the increases in intracellular concentration of Ca++ which is caused by interaction of acetylcholine with the muscarinic receptors on bronchial smooth muscle.

Side Effects

Adverse effects associated with the use of Atrovent HFA may include, but are not limited to, the following:

• bronchitis
• COPD exacerbation
• dyspnea
• headache

Clinical Trial Results

The FDA approval of Atrovent HFA was based on two randomized, double-blind, controlled clinical studies. These studies enrolled males and females ages 40 years and older, with a history of COPD, a smoking history of >10 pack-years, an FEV1 <65% and an FEV1/FVC <70%. In the studies, Atrovent CFC was used: CFC does not contain chlorofluorocarbons (CFCs) as propellants.

Study 1 was a 12-week randomized, double-blind active, and placebo-controlled study in which 505 randomized COPD patients were evaluated for the safety and efficacy of 42 mcg (n=124) and 84 mcg (n=126) Atrovent HFA in comparison to 42 mcg (n=127) Atrovent CFC and their respective placebos (HFA n=62, CFC n=66). Data for both placebo HFA and placebo CFC were combined in the evaluation. Serial FEV1 (as means adjusted for center and baseline effects on test day 1 and test day 85 (primary endpoint) demonstrated that 1 dose (2 inhalations/21 mcg each) of Atrovent HFA produced significantly greater improvement in pulmonary function than placebo. During the six hours immediately post-dose on day 1, the average hourly improvement in adjusted mean FEV1 was 0.148 liters for Atrovent HFA (42 mcg) and 0.013 liters for placebo. The mean peak improvement in FEV1, relative to baseline, was 0.295 liters, compared to 0.138 liters for placebo. During the six hours immediately post-dose on day 85, the average hourly improvement in adjusted mean FEV1 was 0.141 liters for Atrovent HFA (42 mcg) and 0.014 liters for placebo. The mean peak improvement in FEV1, relative to baseline, was 0.295 liters, compared to 0.140 liters for placebo.

The other study was a 12-week, randomized, double-blind, active-controlled clinical study in 174 adults with COPD, in which Atrovent HFA 42 mcg (n=118) was compared to Atrovent CFC 42 mcg (n=56). Safety and efficacy of HFA and CFC formulations were shown to be comparable.