A little more than a year ago, The Medical Letter reported the results of an FDA meta-analysis which found that use of a long-acting beta-2 agonist (LABA) such as salmeterol (Severent) or formoterol (Foradil) in patients with asthma was associated with an increased risk of a composite endpoint of asthma-related death, intubation or hospitalization; the highest risk was in children 4-11 years old.There was no significant increase in risk when a long-acting beta-2 agonist was used with an inhaled corticosteroid.The Medical Letter recommended that long-acting beta-2 agonists should not be used as monotherapy for asthma, especially in children, and that long-acting beta-2 agonists should be used for asthma only in combination with an inhaled corticosteroid, preferably in a fixed-dose combination in the same inhaler.1

Now the FDA has issued new Safe Use Requirements2 and labeling requirements for long-acting beta-2 agonists that include the following: “Stop use of the LABA, if possible, once asthma control is achieved and maintain the use of an asthma-controller medication such as an inhaled corticosteroid.”3

It has not been determined that patients taking a longacting beta-2 agonist in a fixed-dose combination with an inhaled corticosteroid have an increased risk of death or that stopping long-acting beta-2 agonists in such patients will improve long-term outcomes. A controlled clinical trial of these new requirements would be welcome.

1. Long-acting beta-2 agonists in asthma. Med Lett Drugs Ther 2009; 51:1.
2. www.fda.gov/safety/medwatch/default.htm
3. BA Chowdhury and G Dal Pan. The FDA and safe use of long-acting beta-agonists in the treatment of asthma. N Engl J Med 2010; Feb 24 (epub).

Download: U.S. English

The FDA has approved the proton-pump inhibitor (PPI) dexlansoprazole (Kapidex - Takeda), a delayed release formulation of the R-enantiomer of lansoprazole (Prevacid - Takeda), for treating and maintaining healing of erosive esophagitis and for treatment of heartburn associated with non-erosive gastroesophageal reflux disease (GERD).

Cholinesterase inhibitors are now used routinely in patients with dementia. Rivastigmine transdermal system (Exelon Patch - Novartis), a patch formulation of the cholinesterase inhibitor rivastigmine tartrate, has been approved by the FDA for treatment of mild to moderate dementia associated with Alzheimer's or Parkinson's disease. An oral formulation of rivastigmine tartrate has been available in the US since 2000,2 but gastrointestinal adverse effects possibly related to rapidly rising serum concentrations have limited its use.

Recent reports (D Kaye.Clin Infect Dis April 1, 2008;46:iii) indicate that 2 of the 3 components of this year's influenza vaccine (Med Lett Drugs Ther 2007;49:81), the influenza B and A/H3N2 antigens, do not matchup well with circulating strains. The B component is probably not protective. The A/H3N2 antigen in the vaccine probably provides some protection, particularly for high-risk patients. The third component, the A/H1N1 antigen, is protective against circulating A/H1N1 influenza viruses, but these viruses, unlike previous A/H1N1 strains, are developing some resistance to oseltamivir (Tamiflu), particularly in Europe; in the US and Canada, about 5% of influenza A/H1N1 isolates are resistant to oseltamivir in vitro.

Download U.S. English

Paliperidone (Invega - Janssen) has been approved by the FDA in an extended-release formulation for treatment of schizophrenia. It is the primary active metabolite of the second-generation antipsychotic risperidone (Risperdal - Janssen), which is scheduled to lose its patent exclusivity in December 2007.