A major non-event!
Here is an example of some of the unfortunate realities society faces regarding antibiotic development. Depomed, Inc. reports that the FDA has granted approval to market Proquin XR, its antibiotic used for treating uncomplicated urinary tract infections. Basically, this is a commonly used drug called Cipro (ciprofloxacin) repackaged in an extended-release form.
Depomed's earth-shattering medical advance is that unlike Cipro's twice a day dosing, Proquin XR only needs to be taken once a day. The spectrum of activity (the range of different bacteria that it is effective against) is no different than for Cipro and Proquin XR does nothing to increase our armamentarium against increasingly resistant microbes.
A once a day drug would represent a significant advantage over a twice a day drug if there were no others in this class (fluoroquinolones). With greater ease of administration, patient compliance would be expected to be higher and incomplete dosing would be less of a problem. This is important because when a patient fails to complete an antibiotic course this can select for more resistant organisms that may be more difficult to treat later (and that may be passed on to others).
However, there are at least two fluoroquinolones with similar spectrums of activity available in the U.S.: Levaquin (levofloxacin) and Avelox (moxifloxacin) both of which require only once a day dosing.
What this means is that Depomed spent a massive amount of R & D dollars getting FDA approval for a superfluous drug that fails to address any particularly important clinical problems. This makes Proquin XR a classic "me too" drug, a drug that serves no function other than to allow this company to go after market share in an area that already has acceptable alternatives.
I don't begrudge Depomed this decision (well maybe a little as a matter of corporate ethics). It was a business move and they should be allowed to make it. I believe in the benefits of a free market. However, I do believe that this underscores an absolutely critical problem. Society needs better antibiotics to cope with the problem of increasing bacterial resistance. Until companies are given better incentives to develop such drugs, such development will not occur. The public's health will be the worse for it.
I've written before about the gravely serious nature of this problem and some viable solutions. Check it out.
Depomed's earth-shattering medical advance is that unlike Cipro's twice a day dosing, Proquin XR only needs to be taken once a day. The spectrum of activity (the range of different bacteria that it is effective against) is no different than for Cipro and Proquin XR does nothing to increase our armamentarium against increasingly resistant microbes.
A once a day drug would represent a significant advantage over a twice a day drug if there were no others in this class (fluoroquinolones). With greater ease of administration, patient compliance would be expected to be higher and incomplete dosing would be less of a problem. This is important because when a patient fails to complete an antibiotic course this can select for more resistant organisms that may be more difficult to treat later (and that may be passed on to others).
However, there are at least two fluoroquinolones with similar spectrums of activity available in the U.S.: Levaquin (levofloxacin) and Avelox (moxifloxacin) both of which require only once a day dosing.
What this means is that Depomed spent a massive amount of R & D dollars getting FDA approval for a superfluous drug that fails to address any particularly important clinical problems. This makes Proquin XR a classic "me too" drug, a drug that serves no function other than to allow this company to go after market share in an area that already has acceptable alternatives.
I don't begrudge Depomed this decision (well maybe a little as a matter of corporate ethics). It was a business move and they should be allowed to make it. I believe in the benefits of a free market. However, I do believe that this underscores an absolutely critical problem. Society needs better antibiotics to cope with the problem of increasing bacterial resistance. Until companies are given better incentives to develop such drugs, such development will not occur. The public's health will be the worse for it.
I've written before about the gravely serious nature of this problem and some viable solutions. Check it out.
posted by The Medicine Man at 2:00 PM
13 Comments:
Yes,and isn't there also a CIPRO XL by Bayer.
LOL. I didn't even know that but yes, you're right. There IS a Cipro XL. I consider it a badge of honor that I hadn't heard of it!
That makes this all the more ridiculous.
John
Levaquin probably is unnecessarily broad-spectrum for the treatment of uncomplicated cystitis, and Avelox doesn't penetrate the urinary tract in any case. Proquin is just generic Cipro XL...not a great medical advance by any means, I grant you, but I think you may have taken the wrong angle on this.
While I couldn't care much about "Proquin XL" as a drug, I am glad that there is a generic, and therefore hopefully cheaper, version of a perfectly good antibiotic on the market. Cialis and Levitra are "me-too drugs", just like the 100 identical ACE inhibitors and ARBs on the market...a cheaper generic drug, on the other hand, is a good thing.
Point well taken with the Avelox. Wasn't thinking! It isn't used for UTI's.
Levaquin is often used for uncomplicated UTI's although like Cipro, I agree that it probably has an unnecessarily broad spectrum.
Proquin XR is not a generic product. It has a proprietary release system and its current marketing will be based on a brand new FDA drug application.
John
It is seriously being marketed as a non-generic? Well, that is lame. Still, the addition of a second version on the market could still drive down prices (I hope).
-rcm
I have a question based on the discussion in the comments. I'm a biochemist/molecular biologist/microbiologist with an academic interest in the possibility of tailoring antibiotics to specific bacteria. There a number of ways these could be useful as research tools. But I've always wondered if they would be useful in real practice. When you guys say that an antibiotic is too broad spectrum, what do you mean? I've argued that narrow spectrum drugs would be useful for chronic conditions like P. aeruginosa in CF patients or slow infections like TB. But the rest of the time, don't you usually start the regime before the microbiology comes back telling you what the bug is? Or would some kind of class-specific antibiotic be useful to keep things like C. diff blooms down?
If I may offer a trivial observation, part of this is also to be found in the doctor-patient relationship.
I am quite intelligent. In my younger days, I certainly was guilty of the common behavior of incomplete dosing. At no point did any doctor actually discuss with my why I should take every one of them, I was just given them and told to take them.
When you make the reasons for a behavior clear to a patient, then they can make properly informed choices about compliance. No, this does not mean that they all will, but it does increase the chances of it at little cost to the doctor or patient.
This isn't always practical, but when doctors take on that air of a boss, then the natural human tendency for individualism kicks in, and there is a tendency to resist any instruction for which the reasons seem insufficient.
Jim,
When we say that an antibiotic is too "broad spectrum" we generally mean that it is a bigger gun than is needed for a particular purpose.
For most uncomplicated urinary tract infections, older antibiotics like Bactrim or Macrodantin are fine. When you use a big gun like Cipro or Levaquin, you run the risk of having a powerful drug lose its effectiveness prematurely.
Yes, in most cases we treat "empirically" with an antibiotic likely to be effective in the case at hand. We try to use the cheapest, narrowest-spectrum drug initially that is appropriate. (If a patient is seriously ill than we tend to use broader coverage initially.) If the patient doesn't get better then we tend to broaden the antibiotic coverage (or rethink our original diagnosis).
If the patient is getting better but the culture results (which usually take several days to come back) show resistant organisms, we may or may not change the antibiotics. In vitro measures of drug resistance may not reflect actual patterns of resistance in vivo.
John
Nick,
I commend you on your very non-trivial observation. All of us in clinical practice are guilty at times of talking down to patients.
For the reasons you've eloquently noted, this can definitely work against us! It is certainly true that for insightful patients, more explanation rather than less is often indicated.
John
John,
Let me see if I understand your reply. In the clinical setting, broad spectrum isn't so much about which bacterial species are targeted as which constellations of existing antibiotic resistances are out there. So it's a matter of saving the antibiotics where resistance isn't widely prevalent for those cases where other drugs fail to kill off the infection. Even if resistance to penicillin derivatives is very widespread, you'd still try them first because on average many infections are controlled by them.
At the level of individual patients, a bigger gun might have a slightly higher probability of clearing them faster - which depends on the probability that they picked up a resistant bug in the first place. But from a population point of view using the big guns when you don't need them increases the likelihood that resistance to these will arise, so they won't be big guns anymore...and if you don't have any big guns, then the patients who really need them because they get hit by something like MRSA are screwed.
Is that basically correct?
Jim,
We use cheap, narrower-spectrum antibiotics on patients when they are most likely to be effective. You wouldn't use an antibiotic that you didn't think would be effective just because it was cheaper!
We also tend to use more expensive, broad-spectrum antibiotics if the patient is very ill and where a misstep would be catastrophic. Once we get sensitivity data back from the lab, we're apt to narrow our coverage accordingly.
John
My mother-in-law was recently prescribed a one-pill-a-day antibiotic regimen for a lung infection. She balked at the price when she got to the pharmacy (I think it was around ninety dollars), and called the doctor to ask if there were a cheaper alternative. He then recommended a two-pill-a-day regimen that cost her only fourteen dollars. (For the record, she completed the course and is fully recovered.)
By this rule, even though Proquin is technically a "me too" form of Cipro, it may be priced six times higher than Cipro. I understand the importance of maximizing the likelihood that the patient will finish the course, but many patients do not understand. Therefore the health care industry is asking its customers to pay much more for a somewhat amorphous and mysterious benefit, and a benefit to other people some time in the future. The only way this will work is if doctors and pharmacists conceal from patients the existence of the cheaper alternatives.
On the issue of funding antibiotic development, what about the Pentagon? They've got deep pockets, and they would reap the greatest cost/benefit ratio of any group. I can't imagine that there is any more faithful customer of antibiotics than the American soldier, for whom bullets and shrapnel are a daily reality, along with increased exposure to novel pathogens. If I recall correctly, penecillin was discovered years before World War II, but it wasn't until the necessity of the war came along that antibiotic application boomed. If we have to endure life during wartime, can't we create some "collateral benefits"?
Thanks for the post. It's a fascinating issue, and of my favorite type: impossibly complicated and potentially threatening to our very existence.
tompain
I think the selling point for Proquin XR will likely be the absence of GI side effects, which are a frequent complaint amongst Cipro XR users.
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