Colchicine is a medication derived from the Colchicum autumnale plant, commonly known as the autumn crocus, and has been used for centuries to treat inflammatory conditions like gout and Familial Mediterranean Fever (FMF). It was widely available and prescribed for decades without ever undergoing the rigorous safety and efficacy review required of modern pharmaceuticals. Regulators faced a paradox: it was an established treatment that did not meet contemporary standards for quality control and documentation. The shift in the drug’s market availability was not due to a new safety flaw, but rather a deliberate regulatory action designed to standardize all medications.
The Historical Regulatory Loophole
Colchicine was sold in the United States because its market entry predated the country’s modern drug laws. The Federal Food, Drug, and Cosmetic Act (FD&C Act) of 1938 established the requirement that all new drugs must demonstrate safety before being marketed. However, this act contained an implicit exemption for drugs already on the market, essentially “grandfathering” them into continued circulation. This meant manufacturers of long-used substances like colchicine were not required to submit a New Drug Application (NDA) to prove safety.
A subsequent amendment to the FD&C Act in 1962 mandated that drugs must also demonstrate effectiveness, but existing drugs were again shielded from this requirement. Because colchicine had been in continuous use since before these legislative changes, numerous companies continued to sell various unapproved formulations. These products were often manufactured as bulk powder or compounded versions, lacking the standardized quality control and consistent labeling that are hallmarks of the current regulatory process.
Manufacturers operated in a legal gray area, selling a drug that was widely accepted clinically but was not formally recognized as safe and effective by the Food and Drug Administration (FDA). This created a fragmented market where the purity, potency, and dosage instructions could vary significantly between different products. The lack of regulatory enforcement allowed numerous unapproved versions to proliferate, keeping the drug inexpensive and accessible for decades.
The Enforcement Action
The mechanism that ultimately removed the unapproved versions of colchicine from the market was the FDA’s Unapproved Drugs Initiative (UDI), launched around 2006. The UDI was a broad strategy aimed at eliminating all drugs that had escaped modern regulatory scrutiny under the old “grandfather” system. The continued sale of unapproved medications represented a public health concern because they lacked documented evidence for dosage, drug interactions, and manufacturing quality.
Colchicine was specifically targeted because of documented safety concerns, particularly regarding inconsistent dosing practices and labeling. Studies indicated that the lack of standardized guidance contributed to serious adverse events, including fatalities, in some patients. As part of the UDI, the FDA encouraged manufacturers to submit a New Drug Application (NDA) to formally prove the drug’s safety and efficacy. This process would standardize the drug and provide evidence-based labeling.
In 2009, one company, URL Pharma (later acquired by Takeda), successfully completed the required clinical trials and received FDA approval for a standardized colchicine product, named Colcrys. Following this approval, the FDA moved decisively, issuing an order in September 2010 requiring all other manufacturers, distributors, and marketers of unapproved single-ingredient oral colchicine to cease operations. Companies were given 45 to 90 days to stop manufacturing and shipping their unapproved products, effectively clearing the market. This regulatory enforcement action ended the historical exemption, making the newly approved version the only legal option available.
Current Status and Availability
The FDA’s enforcement action immediately created a shift in the market for the drug. Once Colcrys was approved in 2009, the manufacturer was granted market exclusivity, a standard incentive provided to companies that undertake the expense of clinical trials. This exclusivity meant the FDA would not approve any competing generic versions for a specific period, creating a temporary monopoly for the approved product.
With the lower-priced versions completely removed from the market by the 2010 order, the newly approved product became the sole source of single-ingredient oral colchicine. The resulting lack of competition led to an enormous increase in the drug’s price. The price per pill, which was previously mere pennies, skyrocketed to several dollars, with the average wholesale price per prescription increasing up to 16-fold in some cases.
This dramatic price surge made the medication unaffordable for many patients, leading to a measurable decline in its use and, according to some studies, a worsening of gout control among the affected population. While the regulatory action standardized the drug’s safety and dosing, it severely restricted patient access due to the financial barrier. Since the initial enforcement, the market has begun to normalize with the eventual approval of generic versions, such as Mitigare, which has introduced competition and helped to lower costs for some patients.