Sick About Singulair

The New York Times' business section recently reported that despite a second-quarter earnings fall, hurt by lower sales of its cholesterol drugs (specifically Vytorin, see my posts on why you should no longer use this product), Merck actually beat profit forecasts due to good sales of its asthma drug Singulair. Singulair's quarterly sales jumped 16 percent to $1.3 billion. That's a lot of money! Indeed, based on pharmacy data (via drugtopics.com, thanks again Mr. Medsaver for this great resource), Singualir was the 4th most commonly prescribed drug in 2008 at a close to 26 million prescriptions! Moreover, a recent report from the WSJ Health Blog states that Merk is looking to put Singualir over the counter.



I have no ill will towards Merk. It is an American company that has come up with some products that I find beneficial for patients including Fosamax (which is now generic) and Januvia, and they are the makers of two important vaccines: Gardisil and Zostavax. However, I am concerned about high sales of the asthma drug Singulair, because national guidelines state it should not be used as a first line therapy for asthma.



Facts about asthma



According to the American Lung association, in 2007, it was estimated that 22.9 million Americans currently have asthma. Of these, 12.3 million Americans (3.8 million children under 18) had an asthma attack. In 2005, there were 3,884 deaths attributed to asthma. During 2006, 444,000 hospitalizations and close to 1.7 million emergency room visits were attributed to asthma.



In 2007, the NIH released updated guidelines about asthma. Regarding treatment, the guidelines suggest that all asthmatics with persistent asthma (symptoms or rescue medication use more than twice a week) be initiated on inhaled corticosteroids (ICS). ICS's are considered first line treatment for all asthmatics, from babies to children to adults and to the elderly. The reason is based on solid evidence that these agents work the best in improving lung function and decreasing symptoms. Singulair is listed as an alternative agent. Singulair is an anti-leukotriene. Leukotrienes, like histamines, are substances released in an allergic response that cause the airways to tighten up. Thus, Singulair works in the same way that antihistamines work: by treating the symptoms. ICS's work by blocking inflammation which is what causes the release of leukotrienes in the first place. Singulair is not anti-inflammatory, ICS's are. Singulair treats the symptoms, whereas ICS's treat the problem. This is why study after study proves that ICS's are superior to Singulair, and why guidelines place ICS's as first line treatment and Singulair as alternative.





Does Singulair work?
Of course Singulair works. In order for a drug to be approved by the FDA, the drug company has to show that its product is efficacious. The problem is that it has to show that it is efficacious compared to placebo. Thus, Singulair works better than a sugar pill. However, compared to any other asthma medication, it is not as good. Even when added on to an ICS, it is not as good as other add ons, such as long acting beta agonists (LABA's).



Why do physicians prescribe so much Singulair when is not what the guidelines recommend?

This is an extremely important question. Some may chalk it up to drug company marketing. However, all the ICS and ICS/LABA making companies due their job marketing their product as well. I think the main reason has to do with fear of ICS's. Corticosteroids are different than the kind of steroids athletes take. However, they are not without side effects. Earlier studies on older medications showed some growth delay in children, which is why pediatricians may be so reluctant to use ICS's. However, more recent studies showed that for the newer agents, long term use with mild to moderate doses did NOT cause growth delay. In 2002, the NIH reviewed all the literature and determined that at low to medium doses of ICS's, there are NO SIGNIFICANT SIDE EFFECTS. This is when ICS's became considered first line therapy for ALL asthmatics.

The other issue is the convenience factor of a pill vs. an inhaler. Inhaler use is clearly not as easy as taking a pill (Singulair comes chewable for children).

The thought is probably, "it's a once a day pill that might help my patient, and probably won't hurt them, so why not give it try?" The problem with this approach, is the failure to consider the risks of uncontrolled asthma. Uncontrolled asthma leads to ER visits, hospitalizations, and possible even death. Asthma is a serious disease. For patients who have persistent asthma, following the guideline recommendations of ICS's as first line agents is the right thing to do.

What about allergies?

Singulair is also indicated for allergic rhinitis or allergies. As above, like histamine, leukotrienes play a role in allergic rhinitis, and this is why Singulair is used. I have posted about Singulair and allergic rhinitis previously. Basically, there are several treatments for nasal allergies:Non-sedating antihistamines (Claritin, Zyrtec, Allegra), Leukotriene modifiers (Singulair), inhlaed nasal steroids (Flonase or fluticasone, Rhinocort, Nasacort, Veramyst) and inhaled nasal antihistamines (Astepro). Muliple studies that show that fluticasone (Flonase) is better than Singulair, better than Claritin, and several studies that show that the combination of Singulair and Claritin is not better than either agent alone. However, in one study, though the combination of Singulair and Claritin was better than either agent alone, the individual agents were no better than placebo. An excellent review by Dr. Robert Nathan showed that "leukotriene receptor antagonists (Singulair) are sometimes more effective than placebo, are no more effective than nonsedating antihistamines (Claritin) , and are less effective than intranasal corticosteroids in the treatment of allergic rhinitis." Finally, a recent guideline from World Health Organization suggests that for patients with mild, intermittent allergic rhinitis; treatment with non-sedating antihistamines and leukotriene modifiers were both acceptable forms of treatment, but patients with more chronic or bothersome symptoms, inhaled nasal steroids should be used.

Some would argue that having both allergies and asthma together would be a reason to take Singulair. There is no question that treating allergic rhinitis may help with asthma symptoms. However, the killing two birds in one stone approach simply hasn't been proven to be the case. If you have allergic rhinitis that makes your asthma worse, you should take the most effective agent, which is inhaled nasal steroids.





What if I am taking Singulair for asthma?

Singulair has been proven more effective than placebo, and in some individuals controls their asthma and allergies. However, a recent internet survey revealed that about 55% of asthmatics have uncontrolled asthma, and many of them are on regular medications. Asthma control is the key, according to the new NIH guidelines. If your asthma is well controlled on Singulair, then it is probably OK to take. However, there is a theoretical risk that by taking Singulair (treating the symptoms without treating the underlying inflammation), that though you feel well now, your lung function will be worsening over time. More importantly, if you are taking Singulair and your asthma is not well controlled, then you should definitely switch to at least an inhaled corticosteroid, or possibly an agent combining an ICS with a long acting brochodilator (LABA) such as Advair or Symbicort. There are many ways to determine asthma control, including how much rescue medications you are taking and how asthma affects your daily life. The easiest way to determine your asthma control is by taking the Asthma Control Test

4 Things the FDA Should Go After Besides Cheerios

As reported by the Wall Street Journal, the FDA has decided to go after the makers of Cheerios. You can read their warning letter to General Mills here. The issue the FDA has is not that Cheerios doesn't really lower your cholesterol, but that the language on the box, specifically that eating Cheerios can "lower your cholesterol 4% in six weeks" means that Cheerios is intended for the use of lowering cholesterol, and is therefor a drug. Former FDA chair Dr. David Kessler's book "A Question of Intent" covers this topic nicely. He describes his struggle to try and regulate big tobacco. Since tobacco grows naturally, the argument was that it could not have been intended for a specific use. However, Kessler's fight was to show that the companies manipulated natural tobacco and the way it was delivered to cause an intended response, i.e satisfaction and addiction.





There are other foods that can make health claims, and the FDA's letter to Cheerios points out that soluble fiber products can talk about health benefits, as long as they add an "as part of" clause to the packaging. Though Cheerios has this, they feel the more prominent claim on the box (though not stated in the letter, it's basically their entire marketing campaign) is much stronger.





Since Cheerios does have clinical data to support a 4% reduction in total cholesterol, I am less worried about the stating this, but more concerned about patient's perception about what that does to cardiovascular risk. I have so many patients that are at risk for heart disease, warrant lipid lowering medications by any guideline, and yet are so affraid of medications ask if we give something like Cheerios a try first. The problem is that even though Cheerios may lower your cholesterol by 4%, this probably has no impact on your risk for heart attack or stroke. If you look at all of the cholesterol studies (any drug in any population) it is clear that to derive benefit you need at least around a 25% reduction in bad cholesterol to get any gain. Thus, my problem with Cheerios is not their claim to lower cholesterol, but the implication that this will make a bit of difference when it comes to heart attack or stroke.





However, there are several things that the FDA could focus on that, in my opinion, would serve a much greater purpose.





1. Medications approved not as drugs, but devices, so they seem like they work.


My favorite pharmacist blogger Mr. Medsaver recently gave a great example of this in his post regarding Allergen which is marketed under the names Chloraseptic Allergen Block and Little Allergies. These products are approved by the FDA, not as drugs but as devices. There is actually no active medical ingredients. These products are essentially petroleum jelly that you put under your nose. Their is absolutely no data whatsovere to suggest that these products do anything at all. Yet, patients wanting to help themselves or children who suffer from allergies and are affraid of side effects from actual medication will likely spend millions of dollars this year on a product which has never been shown to be effective, and is likely not. The FDA needs to work on this loop hole.





2. Supplements that imply health claims
To me this is a much greater problem. At CVS.com you can get Ez Diet Carb Suppressor Capsules which have no real ingredients that have been shown to actually lose weight. The name implies they work, but a claim is not being officially made. At GNC.com, a reputable supplement company, their Mega Men 50 supplement is a "healthy aging program for men over 50" and should be taken to "support prostate health" "support eye health" and "provides antioxidant protection." The FDA does not consider these claims as serious apparently as Cheerios, because they are stating that they support eye health for example, and not improving your vision. However, I betting that more people spend their dollars on supplements then Cheerios for health improvement. In addition, unlike Cheerios which at least provides breakfast, the evidence for vitamins and supplements are poor. I discuss this more in my previous post Which Vitamin Should I Take?




3. Homeopathic agents that imply anything
Airborne, Head On, etc. Enough said. At least vitamins and supplements have some potential value. These products have no potential benefit, clearly are making claims, and do absolutely nothing. Innocent patients are wasting millions of dollars on these products.




4. e-cigarettes

These products are drugs without question. They ought to be regulated by the FDA and they have not been proven safe in humans. Though the FDA may not be able to do much about products sold over the Internet, e-cigarettes, which are nictoine inhalers marketed as safer alternatives to cigarettes and smoking cessation aids, are being sold in U.S. shopping malls. There sale in the U.S. should be abruptly halted. See more on my previous post.