Generic and Therapeutic Substitutions

I was on the local DC news today regarding generic substitution.

Generic substitution is when your doctor writes for a prescription medication, but the pharmacists substitutes this with a generic medication. This is perfectly legal and, in general, a good thing for patients. For the most part, and for most drugs, the generic is just as good as the brand drug. However, as the news piece points out, there are some instances where the small difference between the generic and the brand name medication may make a difference. These are usually medicines where doses are very small such as hormones (thyroid medications, birth control pills) and medicines that have to be closely monitored. This does not necessarily mean that the generic is worse than the branded medication, but that switching from one to the other could have potential adverse effects.

One of the things that I spoke with the reporter about that is not in the above video (I have control over what I say, but not what they choose to sue), and only got a brief mention by the new anchor after the video was shown was about therapeutic substitution. This is a completely different ball game and a major concern of mine.

Therapeutic substitution is when your doctor writes a prescription for a branded drug and the pharmacist substitutes it not with the generic equivalent, but with a completely different generic drug in the same class. In this case, you are getting a totally different medication. For example, let's say your doctor writes a prescription for Crestor or Lipitor, both very potent cholesterol lowering drugs. You bring this prescription to the pharmacist, but instead of getting Crestor or Lipitor, you get simvastatin, a generic cholesterol medication. The difference here is that where the brand and generic equivalent will work about the same, this is not the case with a therapeutic substitution. Simvastatin will work in many patients but is not nearly as good as lowering cholesterol as Crestor or Lipitor. Thus, if the patient got switched and needed more cholesterol lowering than the simvastatin could provide (which is why I would write Crestor or Lipitor in the first place), that patient's cholesterol levels could be too high despite medication, potentially leading to heart attack and strokes. This is just one of many examples.

The practice of therapeutic substitution is currently illegal, but this could change. In Washington, DC where I practice, there is current legislation pending that would not only allow, but might compel a pharmacist to switch patients to cheaper medication, whether or not they were the same. In the case of DC, this is designed to save the government money from the millions of dollars its spends on prescription medications for our Medicaid patients.

With health care costs so high, physicians should do their best to try and write generic medications when possible. In additions, our pharmacist colleagues can be a tremendous help in figuring out ways to lower the costs of medications by using generics, whether it be a direct generic substitution or even therapeutic substitution. Pharmacist and blogger Mr.Medsaver has been doing this for quite some time, and I routinely read his helpful posts. However, pharmacists are not trained clinicians and do not know (and can not know) all the details of the patient's history or the rationale for the doctor choosing one drug over another. Though the pharmacist's suggestions are always welcome, I do not believe the should be allowed, and certainly not compelled or heaven forbid incentivized, to switch medications within the same therapeutic class. This could be very dangerous for patients.

Stop Using Vytorin!!!!

At the American Heart Association meeting in Orlando, FL they just released the results of the ARBITER 6 HALTS study. No Vytorin was used in the study, but I am sure that all the headlines will mention Vytorin... and for good reason.

Here is the actual study published ahead of press online in the New England Journal of Medicine. Essentially, the enrolled over 200 patients from Walter Reed and Washington Adventist (right in my home town!) who had known heart disease or were at very high risk. These patient were already on a stable dose of a statin (40-50% on simvastatin -half of the Vytorin combination, and 40-50% on Lipitor) with LDL cholesterols (bad cholesterol) under 100 and HDL (good cholesterol) under 50 for men/55 for women. These patients were randomized to receive either Zetia (the other half of Vytorin) or Niacin (though you can get this vitamin over the counter, patients received the extended release prescription version, whose maker is also the sponsor of the study). They were looking to see whether or not there would be difference in progression of atherosclerosis (clogging of the arteries) over 14 months as measured by carotid intima-medial thickness (CIMT), and ultrasound of the neck arteries which seems to be a good measure of plaque buildup in the coronary or heart arteries. News broke earlier this year that the study was stopped early because there was a clear winner, but we didn't know which drug won until now.

Patients who got the Niacin had their good cholesterol raised by close to 20%. bad cholesterol lowered by close to 10%. The Zetia group lowered bad cholesterol by close to 20% but also lowered the good cholesterol too. More importantly, those patients taking the Niacin had a reduction in the plaque buildup, whereas patients taking the Zetia had no change in plaque build up. Surprisingly, and inexplicably, the more Zetia lowered your cholesterol, the more plaque build up patients had. Finally, and most importantly, only 1% of patients in the Niacin group had major cardiovascular events, compared to 4% in the Zetia groups. This was statistically significant.

This trial has broader implications than just the Vytorin issue (which I will get to in a second). It suggests that patients at high risk for cardiovascular disease may have additional benefit beyond lowering their bad cholesterol. Though the addition of Niacin was proven to show benefit, it might be possible that other drugs which raise HDL such as fish oil and fenofibrate (Trilipix) might benefit at risk patients as well.

I have posted extensively on Vytorin in the past. Most of the controversy had to do with the ENHANCE trial which I discussed in my post Vytorin and Zetia: What to do now? Briefly, whereas multiple statin trials have shown that lowering LDL with a statin led to decreased heart attacks and stroke, Vytorin only had data showing it lowered the LDL. Merk, the makers of Zocor (simvastatin), Zetia, and Vytorin (Zocor + Zetia) funded a trial that, similar to the HALT study, looked at CIMT to measure plaque buildup. It compared simvastatin to the same dose of simvastatin plus Zetia, or Vytorin. Though Vytorin lowered cholesterol more that the simvastatin alone, there was no difference in plaque buildup. Defenders of Vytorin said that ENHANCE was not an outcome study (designed to study actual heart attacks and strokes) and that there were no differences in outcomes between the two groups. Though the HALT study was also not designed as an outcome study, findings were consistent AND there was a difference in heart attacks and strokes: about triple the number in the Vytorin group. My initial recommendation was that though Vytorin was really useless, if patients couldn't reach their goal with a potent statin or couldn't tolerate the statin, then using or adding Zetia was reasonable. This is probably still the case. However, in the HALT study differences were seen in HDL (went up for Niacin and down for Zetia), and this may account for some of the difference. For patients whose HDL was low, I will probably be a little more cautious of using or adding Zetia, which may make their HDL go down in addition to their LDL.

Bottom Line: There is no good use for Vytorin, and it may even cause harm, not because of safety, but because the LDL goals achieved with Vytorin may lead to fewer heart attacks that could be prevented with a more potent statin. If you are on Vytorin, ask you doctor about considering a switch.

The Pap Smear: A Symbol for Our Health Care System's Problems

Today the Wall Street Journal and other sources reported on a study from The Annals of Internal Medicine that showed that most US doctors don't know the guidelines of how often women should get a pap smear. More importantly, doctors were doing a lot of pap smears on women who didn't need them. In all the talk about health care reform, reducing costs by eliminating unnecessary testing has been mentioned multiple times. Thus, if we can figure out how to get rid of all of these unneeded pap smears, maybe we can find the cure for our health system's woes.

The results of the study are not surprising to me, as I have seen this in clinical practice. The more I thought about why this is occurring, the more I thought about the pap smear as a symbol of our health care system's problems. So why so many pap smears?

1. Pap smears have saved lives. Cervical cancer used to be a major killer of US women. Now it is rare to hear about a women who has died of cervical cancer. Not true in third world countries when screening is not possible. The fact that we have virtually gotten rid of a cancer with early detection is truly amazing. But the danger here is that it has set up the paradigm that this is true for all diseases and cancers. Recently, breast cancer and prostate cancer screening have come under fire for not really saving any lives. However, even with the data, patients and advocacy groups will not likely take a screen only if proven life saving approach. Breast self-examination has absolutely no data to support this practice, and in young women who are likely to find non-cancerous bumps, may actually be harmful. Yet, this practice is routinely recommended for many young women.

2. Women (and many men) want/expect a yearly physical, and most women believe that a pap smear is part of this. Similar to other types of cancer screenings, there is very little evidence that a routine check up is beneficial. This is not to say that you shouldn't visit your doctor regularly. However, many of the things doctors do during a physical have limited to no value. There are some things that have tremendous value, such as checking blood pressure and weight, and talking about diet, exercise, smoking cessation, etc. However, having the doctor check your whole body every year when your feeling just fine is unlikely to be helpful. Yet, the American public expect a full exam every year. After all, their health care premiums are quite high, so they might as well get checked out. This extends to the pap smear. It saves lives (as above), is part of my regular check up, and I am paying a lot of money for this; so therefore I expect my yearly pap.

3. Physicians have little disincentive to refuse to do a pap smear. The pap smear only takes a few minutes. Trying to take the time to explain #1 and #2 above makes little sense for the primary care physician who is not paid by time spent counselling a patient, but by how many patients she can see. In other words, talking a patient out of an unneeded test actually costs the primary care doc money, because that time could be used for seeing another patient. More importantly, if the physician refuses the pap smear, and the patient goes elsewhere to get the pap smear and is found to have cervical cancer; the physician could get sued placing her entire career in jeopardy!

If pap smears save lives, patients expect/demand them, talking a patient out of an unnecessary pap smear only costs me money and not doing the pap could get me sued, why wouldn't I do a pap smear on every women that wanted one?

4. The pap smear rep reminded me to get the test. The drug companies are not really the problem any more. Every day you read about a drug company laying off employees. This is because most drugs are or will soon go generic and there is little in the pipeline. This is not the case for devices and testing. Big labs have reps that come to physician's offices to discuss the latest fancy new test. Like the drug reps, they bring lunch too. The difference: medical devices and testing though FDA approved are not nearly has heavily regulated as the drug companies when it comes to selling to physicians. Drug reps by law are restricted to saying only what is in their label to physicians. It works a little bit differently for the lab and device reps. As newer tests and devices become available, watch for more of a focus on selling these products. Don't be surprised to see direct to consumer advertisements asking patients to ask their doctors about such and such a test.

5. The experts don't agree. It is very hard to keep up with evidence based guidelines in primary care. It's even harder when there are multiple guidelines, and harder still when they don't agree. For prostate cancer, the American Cancer Society and the American Urological Society say that doctors should test for prostate cancer. The US Preventative Health Task Force guidelines say that we shouldn't. Initially, some of the groups recommended more frequent pap smears, but recently decreased the interval due to evidence that less frequent screening was better. However, with all multiple guidelines that often differ, it is not surprising that so few primary care physicians actually knew what all the experts actually did agree upon. Another issue is that reasons behind differing guidelines have to do primary with politics and money. The Urologists want primary care docs to test for prostate cancer because they make money when the test comes back positive. The government doesn't want you to test for prostate cancer, because testing leads to more testing and treatment which costs them (you the taxpayer) more money.

6. Doctor's don't follow guidelines anyway. Even if there was one clear and definitive guideline for docs to follow, they probably wouldn't. There are likely multiple reasons. Our current Continuing Medical Education system (CME) that is supposed to keep docs up to date is horrible and funded by commercial interest. The stimulus package already gave some money for comparative effectiveness research and there will likely be more money for this in any health care reform bill that passes. However, if docs don't know the results of what is best or what actually works, then the data is not all that useful. It is unlikely that a drug company is going to fund a CME program that shows their drug is not useful. So who is going to fund the dissemination of comparative effectiveness findings? There is also no real incentive to follow guidelines. Again, docs get paid for how many patients they see, not by how beneficial their advice was to patients or whether they gave guideline appropriate care.

Since pap smears don't cost a substantial amount of money, it is unlikely that getting rid of all these unnecessary pap smears is going to put a dent in health care spending. However, the underlying reasons behind the many unneeded pap smears is a symbol of what what's right and wrong about our health care system. We should give this study's findings, and more importantly the reasons behind these findings, a critical look.

Parents: Please Keep Your Children in Booster Seats.

Yesterday, my 8 year old daughter was very upset about our demands that she stay in a booster seat when riding in a car. Her main concern was that most of her friends parents didn't make them ride in a booster seat. My family is vertically challenged, and I explained to her that she needed to be 4'9" in order to wear the belt alone. We even went to the American Academy of Pediatrics web site to show her that I wasn't making this up (she doesn't care that I am an associate professor at a medical school) and I let her try using a seat belt alone in the garage to demonstrate how the belt was practically against her neck. Regardless, she stated that this was not fair, and that even some of her friends who were as tall or even shorter than her were allowed to ride without a booster.

Coincidentally, the AAP's journal Pediatrics (not yet available online, but data via Medpage Today) released a study today updating information regarding the use of booster seats in childre 4 to 8 years old. They collected data for over 9 years including 7,151 children in 6,591 crashes. Most kids (70%) were using a seatbelt alone (no booster). The study found that serious injury including concussions, brain injuries, internal organ injuries, spinal cord injuries, and extremity fractures occurred in 1.15% of children; 1.36% of those wearing seatbelts and 0.67% of those in boosters. or double the risk of serious injury with seatbelt alone. Most of the injuries were head injuries and children wearing seatbelts alone had over double the risk of suffering abdominal injuries.

Thus, this study reaffirms the need to keep young children in booster seats until they are tall enough to wear a seat belt alone, which is at 4'9" which occurs sometime between 8 to 12 years of age. It's not that my daughter minds the booster so much. However, she feels like a "baby" when her friends are allowed to ride without a booster. Parents, (especially my children's friends parents) please keep your kids in booster seats until they are 4'9".

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

Finally! FDA Questions Safety, Quality of Electronic Cigarettes

As reported first in the WSJ Health Blog, the FDA is finally looking into electronic cigarettes, and they don't like what they see. Here is the FDA press release and here is the full report.

I have previously posted on my concerns about the safety of e-cigarettes. These posts are some of my more popular ones, with so many readers not understanding my concern. Their points are that e-cigarettes are at least better than tobacco cigarettes, and nicotine itself is safe, since it is sold over the counter. However, the FDA seems to validate my concerns. Here's what they found.

• In testing 19 products from two manufacturers, investigators found that the majority tested positive for tobacco impurities thought to be harmful to humans.


• In one sample, the FDA’s analyses detected diethylene glycol, a chemical used in antifreeze that is toxic to humans


• Half of the samples appeared to contain known carcinogens


• Some products testing positive for nicotine even though the label said no nicotine was present.

The FDA is also concerned about the appeal of e-cigarettes and the easy availability to children:

These products are marketed and sold to young people and are readily available online and in shopping malls. In addition, these products do not contain any health warnings comparable to FDA-approved nicotine replacement products or
conventional cigarettes. They are also available in different flavors, such as chocolate and mint, which may appeal to young people

Thus, I stand by the statements in my previous posts. Electronic cigarettes are not safe and should not be used to replace tobacco products, nor as a substitute for smoking cessation agents.

Let Google Solve Our EMR problems

The Wall Street Journal reported today that Google was going to launch their own operating systems for PC's competing with Microsoft's dominant Windows platform. Google seems to continuously creating new, innovative and useful products. This very blog is hosted on blogger, which is now a Google product. Since they seem to be doing such a good job, why not let them solve the electronic medical records problem?

EMR's are a big part of President Obama's health care plan. I certainly value the use of EMR's. They provide me the data I need when I need it. They allow me to communicate more effectively with my staff. Using e-Prescribing in our EMR I am able to fill prescriptions faster and more accurately for my patients. Finally, through our EMR, patients can communicate directly with their physicians. (We use Touchworks by Allscripts. I have no vested interest in the product or company)

However, I do not believe that EMR will really save a lot of money. Time is money, and EMR's do not save time. EMR's do improve quality of care. They allow you to do more in a given amount of time, but do not save time., and in fact may add time because you can do more. The best example I can give for non-EMR users is that just in the way that your email and Blackberry have not saved you any time from the days when you relied on phone calls and the US postal service (have they not instead created more work?), EMR's do not save time. Politicians point to cost savings in preventing duplicate work. There might be a few duplicate tests or procedures prevented, but likely not that many and not nearly enough to call investment in EMR's a cost-reducer.

In my post $19 Billion For Health IT-Money Well Spent? I also call into questoin how the stimulus package is funding health IT. Looks like that money went to hospitals to improve exsiting systems, and not to help the primary care physician offset the HUGE cost of implementing an EMR in his or her practice. The software, hardware and support needed for most EMR's cost far more than the average physician practice can afford.

The real issue with EMR's is interoperability. The are many companies that make many products and not too many systems talk to each other. In our hospital alone, we now use up to eight different computer systems to store and retrieve patient information. Your primary care doctors EMR should be able to talk to the Pharmacy's computers, the lab's computers, the hospital's computers, the radiologist's computers, the specialists consulant's computers, etc.

Regardless of whether you support a single payer system or a tax rebate for patients to purchse their own health care; wouldn't it make sense to have one really good EMR that every doctor could use? Wouldn't it be great if this was on a web based platform, meaning that all you would need is a computer (or netbook, or web based mobile phone) and a high speed internet connection and you could have access? Most docs already have that. Wouldn't it be great if interfaces could be created so that all parties "spoke" to each other? Wouldn't it be great if this system could include functionality so that patients could communicate with their physicians, request appointments, and see their lab results?

Who better to create this EMR than Google? The interoperability/interface issue stems from the fact that there are so many proprietary systems. Each company that makes an EMR wants its EMR to be used by everyone. Just throwing money at all of these companies is not going to solve the problem or make EMR's more affordable or usable. The goverment already has a pretty good EMR used in the VA. It works well inside the VA, but doesn't talk to others. Even in a single payer, government run health care system, would you have the goverment re-vamp the VA EMR? Why not go to the pros at Google? They have already started the process with Google Health, though this is a personal health record and not an EMR. They good create a Google Medical record (GMR) that interfaces with their existing Google Health platform. Sure, they would have a monopoly, but in this case the benefits to the public, patients and doctors far outweight the risks. If the Google EMR was supported by the goverment, then you could create restrictions to limit any of their profit.