Posts Tagged ‘FDA’
Gimmee a Pill Part Deux
Is obesity a disease or a condition? If it is a disease, is it chronic or situational? Does obesity raise itself to a problem which requires the might of pharmaceutical research to overcome, or is it a societal problem? What do you do when one third of the United States population is obese? These are some of the questions that the FDA and its committees have been wrestling with lately.
The weight loss industry is a multi billion dollar a year business and as anyone who has read the labels at the health food stores knows, these substances sold as pills are not FDA approved. Their efficacy is also not known or tested, but that doesn’t really matter because if Kim Kardashian said it works, it’s good enough for me. Most of these diet aides contain substances that allegedly increase metabolism like caffeine or guarana which contains twice the amount of caffeine that coffee beans do to provide “the burn”.
At the present time “real” drugs to make people lose weight come in two basic categories. Fat blockers, like the drug orlistat known as Alli and produced by GlaxoSmithKline, is one type. This drug is the equivalent of a movie which goes straight to DVD. This drug went almost straight to over the counter because although it works, it is punitive. The drug works by blocking the absorption of fat in what we eat. It causes a condition much like those individuals who lack pancreatic enzymes and cannot digest food properly. The outcome, if you foul up and eat something you should not, is pretty unpleasant. Be sure to buy extra underwear!
The second class of drugs target serotonin. This was one part of the famous Fen-Phen combo that was pulled by the FDA after reports of valvular pathology appeared far removed from the time frame of study. To make it clear - if a study lasts one year, how do we know what will happen if five years later you are still taking the drug? After taking the drug for many years, some patients developed what clearly was a side effect related to fenfluramine. So many law suits were filed that the company went bankrupt.
Two new drugs have appeared on the horizon, but strike me as lacking what’s needed. The first is a compound called Qnexa which is a combination of phentermine (how original) and topiramate which is an approved drug for seizure prevention and migraine prevention. I do not understand the mechanism of the action, but it appears that this combination allows patients to lose weight. However, it also causes the side effects of and I quote “depression, anxiety, sleep disorders, attention deficit disorders, memory difficulty, language difficulty, increased heart rate and teratogenicity (deformed babies)” to name a few. As Doctor Evil would say “Riiiiiight”.
This drug was not approved at the FDA committee meeting. It is unlikely that it will ever pass the hurdles. Stay tuned for the second drug.
Drugs: From A(pproval) to Z(etia)
I was discussing the use of the drug Zetia before I was interrupted by the FDA so I will now return to that. Zetia is a novel compound that is used either with or without a statin. Zetia works on the lining of the small intestine to block the absorption of cholesterol from the intestines. It is not fully understood why all cholesterol in the body is transported into the intestines to then be reabsorbed into the circulation. It is this step that Zetia blocks and it is how cholesterol is lowered. The cholesterol synthesis pathway is “feedback,” i.e. if the level of cholesterol is lower than the body thinks it needs, the liver will produce more cholesterol. It is this step that the statin blocks so that the combination of a statin and Zetia is a very effective way to lower LDL cholesterol.
This is how Zetia got its approval. It dates back to 2006, when any drug was approved by the FDA if it simply lowered cholesterol. Now the FDA requires a proven clinical benefit before granting approval. Zetia has yet to prove that clinical benefit and that is where the controversy arises. In fact–in every study to date–although the combination of Zetia and statin lowers cholesterol, the endpoints for the study have not been met and Zetia always does worse.
My particular problem with the combination is that it is often used to lower the amount of statin used in individual patients. We have large amounts of data that indicate the higher the dose of statin one takes, the better the outcomes. LDL lowering is an easily measured end point for something we can not easily measure. We don’t care what the level of LDL really is; we want to obtain the lowering of death, myocardial infarction and unstable angina-which is what statins do. The higher the dose of statins, the more effect they have on decreasing the endpoints that truly matter.
Two studies have now used the endpoint of the increase in plaque buildup in the carotid arteries. ENHANCE reported in 2008 and now ARBITER-6 released this past month. Neither study involved clinical endpoints. They did not evaluate whether fewer strokes or myocardial infarctions occurred. They simply determined which group had a better imaging response. In both studies, Zetia failed. In ENHANCE against simvastatin alone and in ARBITER-6 niacin performed better than the combination.
Physicians are divided on how to use this drug. A panel of FDA experts declared that it should be used “as a last resort” to lower cholesterol. The real proof will have to wait until 2013. That is when the results from IMPROVE-IT will most likely be released at the American College of Cardiology meeting. This study started several years ago will randomize 18,000 patients and follow them for a minimum of two and one-half years. The primary end points are death and myocardial infarction. The study uses simvastatin vs. the combination of Zetia and simvastatin.
Your particular use of Zetia is defined by your needs and your doctor’s advice. This is the backdrop against which this drug is prescribed. As always you should discuss your medication use with your physicians.
About the Institute
Browse by Category
- Acute Coronary Syndrome (14)
- Adult Stem / Cell Treatment (10)
- Angioplasty (4)
- Aortic Aneurysms /Stents / Grafts (13)
- Atherosclerotic Heart Disease (12)
- Atrial Fibrillation (11)
- Cardiac Imaging (4)
- Cardiac Surgery (19)
- Carotid Disease (7)
- Cholesterol (51)
- Chronic Angina (13)
- Clinical trials (3)
- Coronary Artery Disease (34)
- diabetes (15)
- Heart Failure (30)
- High Blood Pressure (22)
- Myocardial Infarction (36)
- Pacemaker / AICDs (9)
- Peripheral Artery Disease (5)