Asthma Drugs, Patient Safety And An FDA Order
5 CommentsBy Ed Silverman // June 3rd, 2010 // 7:41 am
In a much-needed effort to burnish their images, drugmakers repeat a mantra about wanting to help patients beat this or that illness, and that patient safety is a prime concern. Yet this week, we are treated to a curious spectacle in which the FDA had to order at least two companies to make anticipated labeling changes for their long-acting beta-agonists, or LABAs, which should never be used alone to treat asthma (see this).
The FDA warning was expected since February, but the agency strengthened its recommendations this week (see the initial and revised alerts). But GlaxoSmithKline - which sells Advair, a $7.8 billion seller - and AstraZeneca, which markets Symbicort, a $2.3 billion product - pushed back (these drugs include a corticosteroid). And so as Reuters points out, the FDA was forced to use its power to change drug labeling for only the eight time since Congress granted that authority three years ago.
The “FDA is ordering the involved companies to make labeling changes capturing these new recommendations,” Badrul Chowdhury, head of the FDA’s pulmonary drugs division, tells Reuters. “Not all of the companies have accepted all the changes…so that’s where the ordering comes in.”
In a statement, Glaxo says it work quickly to include the updated warnings but offered no clue about what it found objectionable. In its own statement, AstraZeneca maintained confidence in the “positive benefit-risk profile” of its med and told patients they “should continue their prescribed medication.”
The drugmakers are, of course, entitled to raise objections. They own these products, including the labeling, and have every right to negotiate as hard as possible to advance their cause. But even with the bottom-line responsbility to generate revenue, the need to strike a balance with patient safety remains. By putting themselves in a situation where the FDA feels compelled to offer a public rebuke, Glaxo and AstraZeneca may have undermined their ability to hold themselves out as patient champions.
Condor
Spot-on, Ed!
Last evening, I covered Merck’s part in this story, as it makes a LABA called Foradil® — and as of February 2010, hadn’t made all the FDA-required label changes, either. Do take a look.
Namaste
Justice in MI
Good to see FDAAA mean something.
patrons99
Let’s think intuitively about the LABAs. What about patients with underlying heart disease on LABAs? Does it make any sense to “flog a failing heart” with long term, long-acting beta agonists treatment? What effect does long term beta receptor stimulation have on the cardiopulmonary reserve capacity? on the number of beta receptors? on the development of tolerance to short-acting beta agonists (so-called rescue inhalers)?
I’d be curious to see a prospective, double blinded, active comparator outcome study between a long-acting inhaled anticholinergic/corticosteroid combination versus a LABA/corticosteroid combination in COPD patients. Alternatively, a head-to-head comparison study between a LABA and a long-acting inhaled anticholinergic, however that would be unethical in a population of asthmatics, where LABAs have shown an increased risk of asthma-related death.
BTW - has anyone seriously looked to see if LABAs are associated with an increased risk of cardiac-related deaths? Unless someone actually looks for bodies, they won’t be noticed.
pharmavet
Patrons, the LABA’S are Beta2 agonists, and do not affect the heart. There are no beta2 receptors in the heart, only Beta 1 receptors. Therefore these drugs would not be expected to exacerbate cardiac disease.
patrons99
Sorry Vet - you are quoting the conventional wisdom, which isn’t always correct. There is a growing body of literature which shows that these drugs do exacerbate cardiac disease.
See an article titled “Diagnostic and Therapeutic Challenges in Patients With Coexistent Chronic Obstructive Pulmonary Disease and Chronic Heart Failure” by Thierry H. Le Jemtel, et al. In J.Am.Coll.Cardiol. 2007;49;171-180
http://content.onlinejacc.org/cgi/reprint/49/2/171.pdf
Deleterious cardiovascular effects of inhaled B2R agonists, the mainstay of COPD therapy, are now increasingly recognized. Recent meta-analysis of 5 single-dose and 6 longer-duration trials of B2R agonists has underlined their adverse cardiovascular effects in COPD patients (103). Therapy with inhaled B2R agonists is associated with an increased risk for CHF decompensation (adjusted OR 3.42, 95% CI 1.99 to 5.86) and all-cause mortality in patients with CHF (104,105). Inhaled B2R agonists induced adverse cardiac effects in COPD patients with pre-existing cardiovascular disease (106). The adverse effects of B2R agonists are likely to be exacerbated in COPD patients with coexistent CHF.
103. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis.
Chest 2004;125:2309 –21.
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