An Ancient Medicine Meets Modern Regulation
Colchicine, an alkaloid compound derived from the autumn crocus plant (Colchicum autumnale), has been used for millennia to treat joint swelling [1.8.1, 1.8.4]. Its use for gout was recorded as far back as ancient Egypt [1.8.3]. Despite this long history, oral colchicine was sold for decades in the United States without formal Food and Drug Administration (FDA) approval [1.4.1]. This changed under the FDA's Unapproved Drugs Initiative, which aimed to ensure all marketed drugs meet modern standards for safety and efficacy [1.4.6].
In 2009, the FDA approved the first single-ingredient oral colchicine product, Colcrys, for treating acute gout flares and Familial Mediterranean Fever (FMF) [1.4.1]. This approval was based on new studies which, importantly, showed that a lower dose was as effective for gout flares as the traditionally higher doses but with significantly fewer side effects [1.4.1]. Following this approval, the FDA ordered manufacturers to stop making and shipping the unapproved versions in 2010 [1.3.2, 1.2.4]. This action effectively removed the old, un-tested generic colchicine from the market, but not the drug itself [1.3.1].
The Impact of Market Exclusivity
The FDA's action granted the manufacturer of Colcrys a period of market exclusivity, making it the only legal version of oral colchicine available for a time [1.3.1, 1.3.4]. This led to a dramatic price increase, with the cost per tablet jumping from around $0.09 to approximately $5.00 [1.3.4, 1.9.2]. The sharp rise in cost was associated with a decrease in the use of colchicine and an increase in emergency department visits for gout, suggesting that the price hike may have negatively impacted disease control for some patients [1.3.3, 1.3.1]. The FDA justified its action by citing safety concerns, including fatalities from drug interactions (like with the antibiotic clarithromycin) that were not described on the labels of the unapproved products [1.4.4, 1.9.4].
Current Availability and Approved Uses
The market exclusivity period for Colcrys has since ended, and FDA-approved generic versions of colchicine are now available in the U.S., which has helped to lower the price [1.3.1, 1.5.1, 1.5.2]. While the branded version of Colcrys has been discontinued, its generics remain on the market [1.5.5].
Today, colchicine is a prescription-only medication [1.5.6]. The FDA has approved it for several specific indications:
- Gout Flares: For treating acute attacks and for prophylaxis (prevention) against flares [1.6.1, 1.6.6].
- Familial Mediterranean Fever (FMF): A genetic inflammatory disorder, for which colchicine is approved for use in adults and children aged four and older [1.6.1, 1.6.4].
- Cardiovascular Disease Risk Reduction: In 2023, a low-dose formulation (Lodoco, 0.5 mg) was approved to reduce the risk of heart attack and stroke in adults with established atherosclerotic cardiovascular disease [1.3.5, 1.6.6].
Comparison of Colchicine Formulations
| Feature | Unapproved Colchicine (Pre-2010) | Branded Colcrys (Post-2009) | Current Generic Colchicine |
|---|---|---|---|
| FDA Approval | No | Yes [1.4.1] | Yes [1.5.2] |
| Dosing Info | Not standardized; often high doses | FDA-verified lower, effective dose [1.4.1] | Follows FDA-approved guidelines |
| Safety Labeling | Lacked drug interaction warnings [1.4.1] | Included crucial interaction warnings [1.4.4] | Includes all required safety warnings |
| Typical Cost | ~$0.09 per pill [1.9.2] | ~$5.00 per pill [1.9.4] | Varies, but significantly less than peak brand price [1.5.1] |
| Market Status | Removed from market [1.3.2] | Discontinued, replaced by generics [1.5.5] | Widely available by prescription [1.5.1] |
Off-Label Uses and Mechanism of Action
Beyond its approved uses, colchicine is prescribed off-label for a variety of inflammatory conditions due to its mechanism of action. It works by inhibiting the function of microtubules, which are essential components of cells, particularly immune cells like neutrophils [1.8.3]. This action disrupts inflammatory pathways [1.6.5].
Common off-label uses include:
- Acute and recurrent pericarditis (inflammation of the sac around the heart) [1.6.1].
- Behçet's disease [1.3.5].
- Pseudogout [1.6.1].
- Various dermatologic conditions, such as dermatitis herpetiformis [1.6.1, 1.6.3].
Conclusion
In summary, colchicine was not taken off the market entirely. Rather, the market was transformed. The FDA removed unapproved, un-tested versions due to safety concerns and to enforce modern drug approval standards [1.2.2]. This led to a temporary monopoly with a high-priced branded product, but the market has since opened to more affordable, FDA-approved generic versions [1.3.1]. Today, colchicine remains a vital, prescription-only medication for gout, FMF, and cardiovascular risk reduction, with its safety and efficacy now supported by FDA review.
Visit the FDA website for more information on approved drugs.
