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Spotlight on Colchicine: The Colcrys Controversy
A very old drug gets new marketing exclusivity — at what cost?
On April 16, 2010, we summarized an article on an industry-sponsored randomized trial of colchicine for acute gout flares (JW Gen Med Apr 16 2010). But why did a drug company choose to perform this study? The answer to that question sheds light on a new controversy surrounding an old drug.
In 2006, the FDA launched the "Unapproved Drugs Initiative," which targeted old drugs that had never been approved by the FDA. The rationale was that older unapproved drugs, including colchicine, deserve as much scrutiny for efficacy and safety as do newer drugs. In response to this initiative, the drug company URL Pharma decided to conduct pharmacokinetic and clinical research on colchicine with the intention of bringing it to market as a brand-name product. The clinical trial covered by Journal Watch General Medicine was sponsored by URL Pharma and was a key factor in the FDA's approval of brand-name colchicine (Colcrys) in 2009.
In that trial, patients with acute gout were randomized to receive an oral "low-dose" colchicine regimen (1.2-mg dose initially, followed by a single 0.6-mg dose 1 hour later), a "high-dose" colchicine regimen (1.2-mg dose initially, followed by 0.6 mg hourly for 6 hours), or placebo. At 24 hours, patients in the low-dose group were significantly more likely than placebo recipients to report a 
50% reduction in pain (38% vs. 16% of patients), and side effects were similar in those two groups. In contrast, patients who received hourly dosing for 6 hours had substantial gastrointestinal toxicity but no additional benefit compared with low-dose patients.
The controversy enters the picture here: URL Pharma has been given market exclusivity for 3 years, and companies that produce "nonapproved" colchicine — the products that we've prescribed for decades — are required to phase out production in 2010. Patients will experience this transition as an extraordinary increase in the cost of the drug: Colcrys sells for US$5 per pill, whereas nonapproved colchicine costs pennies per pill.
URL Pharma, the FDA, and healthcare professionals (notably the physician leadership of the American College of Rheumatology) have been engaged in a rather testy debate about these developments. The drug company and the FDA defend their position that efficacy and safety are enhanced because Colcrys is manufactured with FDA oversight and because the prescribing information provides guidance on indications, dosing, and drug interactions. In contrast, the American College of Rheumatology contends that, with responsible prescribing, nonapproved colchicine is safe and effective and that patients who cannot afford Colcrys will suffer. URL Pharma has countered with a program to assist low-income patients.
Practical clinical issues have been overlooked in this debate. The FDA-approved prescribing regimen for Colcrys in patients with acute gout flares is the low-dose regimen from the randomized trial — 1.2 mg initially, followed by 0.6 mg at 1 hour — and nothing else. In the clinical trial, assessment of efficacy ended at 24 hours, because providing ongoing placebo for a painful condition was considered to be unethical. However, most colchicine-treated patients still had substantial pain at 24 hours. How should we manage those patients, who will need further treatment? Switching to a nonsteroidal anti-inflammatory drug (NSAID) or prednisone makes no sense: Most clinicians consider using colchicine for acute gout precisely in patients with contraindications to NSAIDs or prednisone, which are the usual first-line oral treatments. Stated another way, why would we pick an initial treatment regimen that likely will require "rescue" therapy within 24 hours? A 1-week comparison between a low-dose colchicine regimen and a standard NSAID regimen would have been far more clinically relevant than the comparison in the published study.
In the end, I doubt whether the marketing of Colcrys will change the way most of us manage acute gout flares. Indeed, clinicians generally prescribe colchicine not for acute gout but rather for long-term prophylaxis. In fact, the FDA has approved Colcrys for prophylaxis at a dose of 0.6 mg once or twice daily. It's the cost of long-term prophylaxis — $1800 to $3600 per year at full price — that will likely have patients and clinicians scrambling during the next few years. For more on this topic, we invite you to listen to our interview with Aaron S. Kesselheim, MD, JD, MPH (Brigham and Women's Hospital, Boston, MA).
The New England Journal of Medicine recently published an essay by Dr. Aaron S. Kesselheim and Dr. Daniel H. Solomon on the regulatory aspects of the Colcrys controversy (N Engl J Med 2010; 362:2045). The perspectives on Colcrys of URL Pharma and the American College of Rheumatology are available free of charge.
Published in Journal Watch General Medicine June 10, 2010
Reader Remarks:
Review and add to remarks on this article
- colchicine
Sidney Reiff, 14 Jun 2010 2:04 PM EST
For the name "colchicine" to become proprietary property after being used for untold number of years seems ridiculous. It is... [more] - Colchicine
Martin J Chevian, 14 Jun 2010 2:04 PM EST
I sent the FDA a note asking who went to bed with whom on this deal. No common sense! I... [more] - Colcrys
Dwight R. Robinson, Mass Gen Hospital, 14 Jun 2010 2:04 PM EST
This is a regrettable misuse of the regulatory system. The FDA should enlist better advice than it apparently had. - Too bad URL Pharma is a two bit company
Ronald L. Hirsch, 14 Jun 2010 2:04 PM EST
If they had any decent products we could boycott their other products. This is a crime against humanity, pure and... [more] - Colchicine for dry-eye sindrome and Lewis body dementis
Jose Gros-Aymerich, Asistencia Medica Valdebernardo, Madrid, Spain, 14 Jun 2010 2:04 PM EST
Encouraged by comments from an old USA established physician, some of my female menopausal patients took Colchicine for relievement of... [more] - LB Dementia an Colchicine
José Gros-Aymerich, Asistencia Médica Valdebernardo, Madrid, 17 Jun 2010 8:06 AM EST
Sorry, I meant Lewy bodies dementia, that can be related to deposition of an Amyloid-like substance, and Colchicine does show... [more] - Government Supported Rip Off- nothing New Here
A Pharmacist, Hospital, 23 Jun 2010 10:48 AM EST
Again our government has failed us.No need for me to elucidate. Our founding fathers knew when they forewarned "one day... [more] - Colchicine [Colcrys]
E.L. Cooper, Retired, 1 Nov 2010 2:24 PM EST
Specialty: Inactive (Retired)
Colchicine has been around for ages. I have used it for about 20 years. Another example of government knows best.... [more] - Colcrys
Richard H. Pollen, MD FACP FACE, Potomac Physican Associates, 3 Nov 2010 3:34 PM EST
Specialty: Endocrinology Diabetes Metab
Outrageous-- downright theft of a material that's been in the public domain for 150 years. Saying that's ok because they... [more] - colchicine
Patricia B Grohman, 9 Nov 2010 10:57 AM EST
Specialty: Unspecified
I have been taking colchicine for 6 years with no side effects or gout flairups. Price..$ 5-15.00. Now it will... [more] - What Next
B.A. Wattum, 18 Nov 2010 4:31 PM EST
Specialty: Pain Medicine
First it was the IV colchicine that they pulled from the market, which had some merit, but I have not... [more] - Concerned Father of Two Sons with Familial Mediterranean Fever Who Need Colchicine
Charles A. Matarasso, 19 Nov 2010 11:20 AM EST
Specialty: Unspecified
As the father of two boys, ages 6 and 14, who take 45 and 60 tablets a month respectively, I... [more] - greed
R Krablin, MD, Gettysburg Internal Medicine, 30 Nov 2010 1:05 PM EST
Specialty: Internal Medicine
This can only be greed on the company's part and frank undefensible craziness on the FDA's part. OK seek an... [more] - A New Low in Corporate Owned Government Corruption
Linda L. Paul, 6 Dec 2010 7:54 AM EST
Specialty: Geriatric Medicine
IF you ever doubted that we have an immoral corporate owned government here is your proof. That a corporation would... [more] - HOW MUCH IS TO MUCH?
Walter J. Carson, 6 Dec 2010 7:56 AM EST
Specialty: Unspecified
How much Money must we spend to keep a suffer of Gout from severe Pain? In June of 2010 I... [more] - colchine
Edward J Ferraro, 20 Dec 2010 8:06 AM EST
Specialty: Unspecified
I have used colchine for 20 years with great results. If the federal govt does this with one pill, how... [more] - Colchicine wasn't Broke; don't fix it.
H. Jack Wooldridge, 31 Jan 2011 8:05 AM EST
Specialty: Hospitalist
I was surprised to find my Colchicine Rx was changed to Colcrys. As an experienced Colchicine user I want to... [more] - Colcrys by URL Pharma--a classic rip-off!
Lewis B. Morgan, 8 Feb 2011 10:45 AM EST
Specialty: Inactive (Retired)
I have taken colchicine for at least 30 years, whenever I feel a gout attack coming on. I have never... [more] - Counter productive policy
David Kull, 22 Feb 2011 12:47 PM EST
Specialty: Unspecified
Patients -- including me -- will be forced to go outside the country for affordable colchicine, where they will face... [more] - Ancient Egyptians used colchicine
B. E., 25 Feb 2011 1:18 PM EST
Specialty: Unspecified
Colchicine is an ancient remedy for gout and until now has been easily available at a fair and reasonable price.... [more] - What a classic case of government ripoff!
Ramon Torres, 7 Mar 2011 12:47 PM EST
Specialty: Unspecified
I've used Colchicine Tabs 0.6 for years costing me only $10 through Medco mail-in for a 90-DAY supply. Yesterday, my... [more] - Colchicine vs. Colccrys
Thomas R. Kelley, 14 Mar 2011 11:05 AM EST
Specialty: Unspecified
This is an absolute sin...to take a drug that worked and was reasonably priced and turn it into a cash... [more] - colchicine
Charles Davy, 15 Mar 2011 12:53 PM EST
Specialty: Clinical Pharmacology
I am trained as a clinical pharmacologist. My sister-in-law called me to say that the colchicine my father-in-law is taking... [more] - And our health care system isn't broken???
Tim Bohrer, 23 Mar 2011 7:46 AM EST
Specialty: Other Specialty
Well, well. A test not representative of past or expected practice (anyone out there stop taking it before the symptoms... [more] - Money over the health of the public
Lil Blue, 30 Mar 2011 8:29 AM EST
Specialty: Psychiatry
I have been on Colchicine for over 2 years now. Since being on it, I have not had any episodes... [more] - Human lives used to jump-start economy
Dr K, 6 Apr 2011 12:30 PM EST
Specialty: Public Health/Gpm
As one who has taken 3 colchicine per day for more than 25 years, and who will always need to... [more] - colchicine.
paul a duchastel, toronto,on,canada, 11 Apr 2011 11:09 AM EST
Specialty: Family Medicine
From a recent conference on stem cells in cardiac disease,it was apparent these treatments are available in most countries even... [more] - Colcyrs - Outright Political Corruption
Joe Benneteto, 19 Apr 2011 11:43 AM EST
Specialty: Pain Management
Just found out my 60 tab script went from $10 to $384. I have taken one .6 mg tab of... [more] - colchicine
Bud Rofheart, 19 Apr 2011 11:43 AM EST
Specialty: Unspecified
I was told that the original colchicine can be purchased in Canada at its original low price. - colchicine
Burton Fletcher, NYC, 9 May 2011 7:39 AM EST
Specialty: Internal Medicine
An obscene example of an FDA dominated by big pharma dollars. Disgusting. The purpose of government is to protect the... [more] - Colchine versus Colcyrs
LP Talbert, 11 May 2011 12:45 PM EST
Specialty: Palliative Medicine
This is in response to the latest racket that the drug companies have schemed with the FDA's help.
My 82... [more] - The role of colchicine in the treatment of gout
Norman M. Canter, M.D., 1 Jun 2011 10:58 AM EST
Specialty: Inactive (Retired)
Colchicine continues to be indicated at the first sign of a gout flare. It has disadvantages as prophyllaxis against flare.... [more] - Colcrys less effective than colchicine
Stephen E. Goldfinger, 9 Nov 2011 2:54 PM EST
Specialty: Gastroenterology
As a physician caring for many patients with familial Mediterranean fever, I have heard, of course, about the egregious jump... [more] - Colchicine
Thomas E Smith, 27 Dec 2011 12:00 PM EST
Specialty: Clinical Genetics
The FDA it seems should be taken to task on this. Only the United States Patent and Trademark office can... [more] - Colcrys
Saja Mae, 6 Jan 2012 11:52 AM EST
Specialty: Diabetes
My 85 year old grandmother had been taking colchicine for years for her gout. When she was forced to switch... [more]
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