Pharmacology Update

Beclomethasone Dipropionate HFA Inhalation Aerosol (QVAR—3M)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

A new steroid inhaler for the treatment of asthma has been released in a nonchlorofluorocarbon (CFC) metered dose form. Beclomethasone dipropionate has been reformulated in a nonozone-depleting propellant, hydrofluoroalkane-134a. The new formulation is a solution rather than a suspension, resulting in smaller particle sizes and better airway deposition. The product is manufactured by 3M Riker and comarketed by Johnson and Johnson as QVAR. The product represents the first hydrofluoroalkane (HFA) inhaled corticosteroid and the second HFA product following albuterol-HFA approved in the United States.

Indications

Beclomethasone-HFA (BDP-HFA) is indicated for the maintenance treatment of asthma as prophylatic therapy in patients 12 years of age and older. It is also indicated for asthma patients who require systemic corticosteroid administration where the addition of BDP-HFA may reduce or eliminate the need for systemic corticosteroids.1

Dosage

The recommended starting dose for BDP-HFA is 40-80 mcg twice daily in patients on bronchodilators alone. For patients previously on inhaled corticosteroids, the recommended starting dose is 40-160 mcg twice daily. If adequate response has not been achieved after 3-4 weeks, a dose increase should be considered. The maximum dose is 320 mcg twice daily.1 For stable patients maintained on systemic steroids, a reduction in steroid dose may be considered after 1-2 weeks of therapy with BDP-HFA. Systemic steroid withdrawal should be done slowly and each decriment should not exceed 2.5 mg of prednisone or equivalent.1

The manufacturer indicates that QVAR does not need to be used with a spacer.

BDP-HFA is supplied as 40 mcg or 80 mcg in 7.3 g canisters providing 100 actuations.

Potential Advantages

The HFA formulation provides much smaller droplets compared to the CFC formulation. About 55-60% of the actuated dose of BDP in the HFA formulation is deposited in the lungs compared to 4-7% with the BDP in the CFC formulation.2 In general, CFC and dry powder formulations deposit about 5-30% of the drug in the lungs with the remainder deposited in the oropharynx. About one-half the dose of BDP-HFA is needed for asthma control compared to BDP-CFC.3,4 BDP-HFA may have a more favorable therapeutic ratio than BDP-HFA as the greatest systemic availability did not appear to be associated with greater adrenal effects at the same dose of BDP-CFC.5,8 This was based on the affect on 24-hour urinary free cortisol comparing doses of 800 mcg per day of BDP-HFA and BDP-CFC for 14 days.8 HFA does not contain chlorine, does not deplete ozone, and has a shorter life in the atmosphere than CFCs.5 BDF-HFA is a solution and, as such, does not have to be shaken before use and provides a consistent delivery of drug throughout the life of the inhaler.

Potential Disadvantages

The most common side effects are headache (25%) and pharyngitis (27%).1 All inhaled corticosteroids have shown dose-related systemic side effects. These include adrenal suppression, growth suppression in children, increased risk of osteoporosis, development of posterior subcapsular cataracts, and thinning and bruising of the skin.6 The doses per actuation between QVAR and current beclomethasone products (Vanceril, Beclovent) are similar, 40 or 80 mcg for QVAR and 42-84 mcg for Vanceril and Beclovent. Care must be taken to avoid confusion over dosing which may result in a higher than optimal dose of QVAR.

Comments

QVAR is the reformulation of a commonly used inhaled corticosteroid, beclomethasone. The HFA (1,1,1,2 tetrafluoroethane) formulation is more environmentally friendly and provides a much smaller particle size (1.1 microns vs 3.5 microns) and better lung penetration. BDP-HFA is about twice as potent as BDP-CFC. Patients switched from BDP-CFC to BDP-HFA should begin with one half the previous dose.7 Studies comparing QVAR to other inhaled steroids are limited. The average cost per day ranges from about $1 to $2.

For an equivalent dose, the 80 mcg strength is about 60% less costly than the 40 mcg strength ($1.60-3.30). QVAR prices are generally competitive with the other inhaled corticosteroids.

Clinical Implications

CFCs are being phased out as common propellants for aerosols. Alternative propellants include powder inhalers (budesonide) and hydrofluoroalkanes (albuterol HFA). Inhaled steroids continue to be the mainstay antiinflammatory drugs for the management of mild-to- severe persistent asthma. QVAR provides an environmentally safe, twice-a-day alternative to the other inhaled steroids on the market.

References

1. QVAR Product Information. 3M Pharmaceuticals. September 2000.

2. Leach CL, et al. Eur Respir J. 1998;12:1346-1353.

3. Busse WW, et al. J Allergy Clin Immunol. 1999;105: 1215-1222.

4. Gross G, et al. Chest. 1999;115:343-351.

5. Thompson PJ, et al. Respir Med. 1998;92(Suppl A):
33-39.

6. Lipworth BJ. Arch Intern Med. 1999;159:941-955.

7. Demedts M, et al. Int J Clin Pract. 1999;53:331-338.

8. Harrison LI, et al. J Pharm Pharmacol. 1999;51:
263-269.