Search This Blog

Follow by Email

Monday, November 29, 2010

Marijuana, Darvocet, Colchicine and the ineffective politics of medicine

The Food and Drug Administration (FDA) has made two bold steps in the last month. They have asked the manufacturers of pain medications containing the mild opiate propoxyphene (Darvon) to voluntarily take these products off the market, and they have removed from the market all generic forms of the drug colchicine that is used to treat gout.

Initially, this all seems ridiculous. Both of these drugs are nearly ancient, with a track record of successes, failures and side effects that goes back decades.  On further examination, it still seems pretty stupid, though quite a bit more complex.

We'll start with propoxyphene, the pain reliever.  Over the years propoxyphene has been used as a milder, less sedating option for pain that was too severe to respond to acetaminophen or anti-inflammatories. Studies showed, however, that its pain relieving effects were actually no better than plain acetaminophen. Unfortunately, patients thought that it helped significantly more than plain acetaminophen and their doctors also thought that it worked pretty well. It was not nearly as addictive as hydrocodone or other opiates and very old people could often take it without becoming too dopey. It also had an unexpected and very useful off label use as a treatment for restless leg syndrome.  In overdose, however, it was more likely to be fatal than some other mild opiates and because of its metabolism, more difficult to reverse with the medications we have to reverse opiate overdose. The final nail in its coffin was a finding that it changed the electrical conduction in the heart, even at normal doses, and that can lead to sudden death. There are some people for whom, in my experience, nothing else works, and for these people the loss of the drug will be a major blow.

On to gout. Gout is one of the oldest described diseases, and is characterized by an extremely painful swelling of joints, frequently in the big toe or feet, caused by an excess of uric acid in the blood.  The condition can be hereditary and can be worsened by using many common medications.  It can respond to many medications that reduce inflammation, but often these medications are too dangerous. Colchicine is an alternative and has been cheap and effective for many decades. About 8.3 million people have gout, and a sizable minority of these patients used colchicine to prevent attacks or treat acute joint pain. Colchicine has been around so long that the FDA never did any studies on it and so little official science has existed regarding its use, other than the huge personal experience of millions of physicians and patients who have used it over the years.  The FDA started a program to study old drugs, in 2006, and the company URL Pharma undertook to do the studies to see what effective doses were and what were the potential pitfalls of using it.  We had known that high doses of this drug caused diarrhea and could effect the bone marrow in some people, but the new science also informed us of some medications that, when taken in combination with colchicine, could make it more toxic. In return for doing this research, the FDA granted this company exclusive rights to sell the drug for the next 3 years, and as of right now, or pretty soon, the brand name of this drug, "colcrys" will be the only version available, and the cost will go from pennies a pill to over 5 dollars a pill. 

If 1 in 10 patients with gout took this drug as a preventive medicine, 1 pills twice daily, the cost to the US to provide this medication rather than the generic would be about 2.3 billion dollars. This brand name drug is no safer, and in fact no different than the generics that have been available.

So what to do? A person can still buy propoxyphene products online or in Canada or Mexico, but a physician who condoned this would be a sitting duck for a suit if the patient overdosed or had a heart arrhythmia. From what I read, the actual risk of heart arrhythmias may be unknown, and clinically there has been no suspicion of this particular danger over the many years it has been used.  A person can still buy generic colchicine in this same way, but it looks like the online cost has already risen significantly just since the press releases have come out letting us know of the recent changes.

What could we have done differently to reduce suffering and make good choices in situations like this? Propoxyphene has been on the chopping block for some time, but research funded, not by drug companies, but possibly through non-proprietary organizations might have given us more information on appropriate uses for it and who, in particular, should not take it due to heart risks.  Certainly, with regard to colchicine, academic research on the drug could have saved consumers, and the country as a whole, a significant amount of money. Certainly such research would cost much less than the 2.3 billion dollars yearly that represents the difference between brand name and generic colchicine.

And where does marijuana come into this whole story?

Inhaled cannabis has a very long track record of medicinal use, and has been studied extensively. It remains mostly illegal in most states, and in general is an underused resource for conditions such as irritable bowel syndrome, nausea and various forms of chronic pain.  Since most research and marketing of medications is done by pharmaceutical companies, and marijuana is so easy to grow as to be generally unprofitable to a pharmaceutical company, this drug remains in a kind of limbo where legitimate use of it is difficult.  An oral preparation of this, Marinol, is available by prescription, but is in fixed doses and works more slowly and is less easy to titrate than the simple burned and inhaled leaf.  These pills not only don't work as well as inhaled marijuana, but they also cost significantly more, even than the artificially inflated cost of the illegal leaf.

Pharmaceutical companies have, nevertheless, been very effective in bringing novel and innovative medications to general use quickly and efficiently. Research at Universities is very slow compared to the pace at a well funded, for profit company where researchers are professional and the profit motive makes people work hard. The important issue, here, is to maintain academic alternatives that allow research on drugs that will never be money makers.

No comments: