Australia's Caution Reflected in LABA Debate

The US Food and Drug Administration (FDA) has announced a requirement for product labeling to warn that long-acting beta2-agonists (LABAs) should not be used alone for the treatment of asthma, but only in combination with a corticosteroid. These changes reflect the foresight of Australia's cautious guidelines to asthma management, which have not allowed the stand-alone use of LABAs for over fifteen years.

Concerns over the use of LABAs as a monotherapy first arose in 1996, when the Salmeterol Multicenter Asthma Research Trial (SMART trial) showed a possible increase in respiratory and asthma-related deaths in an African American subpopulation. The US Food and Drug Administration (FDA) initially supported the continued use of LABAs, with the addition of a warning on product labeling. However, further reviews have found a significant increase in the risk of serious worsening of asthma leading to death and hospitalization, for patients treated with LABAs alone.

"In Australia, LABAs can only be prescribed in combination with an inhaled corticosteroid (ICS)" comments Lisette Oversteegen, Datamonitor's senior healthcare analyst. This restriction has been in place as early as 1994, as evidenced by the Therapeutic Goods Administration's (TGA) Public Summary document updating Serevent's (GlaxoSmithKline; salmeterol) approved indications to include only patients also receiving inhaled or oral corticosteroids. This point was reiterated in the June 2004 Australian Adverse Drug Reaction Bulletin, which referred both to the products' official labels and the National Asthma Council Australia guidelines.

Several companies are still developing novel once-daily LABAs, which would be a major improvement over the currently available twice-daily products. However, it is unlikely that the companies involved will apply for an asthma label, but would rather focus on approval for Chronic Obstructive Pulmonary Disease (COPD), in which no adverse events have been recorded with LABA monotherapy and unmet needs are still high.