U.S. flag An official website of the United States government
  1. Home
  2. Drugs
  3. Guidance, Compliance, & Regulatory Information
  4. Enforcement Activities | FDA
  5. Unapproved Drugs and Patient Harm
  1. Enforcement Activities | FDA

Unapproved Drugs and Patient Harm

FDA uses a risk-based approach to focus resources on drugs that pose the highest threat to public health. Unapproved drugs have many risks, including:

  • unproven and untested drug formulations with excipients and other inactive ingredients that have not been reviewed by FDA for safety
  • labels and prescribing information that has not been reviewed by FDA for accuracy and completeness
  • unknown manufacturing processes
  • unexpected and undocumented safety concerns due to lack of rigorous pre- and postmarket safety surveillance
  • lack of evidence the drug is effective for its intended use

Since FDA implemented its unapproved drugs program in 2006, hundreds of potentially unsafe unapproved drugs have been removed from the market. The following are examples of adverse events, including deaths, associated with unapproved drugs:

  • Quinine sulfate: Between 1969 and 2006, FDA received 665 adverse event reports, including 93 deaths, associated with quinine sulfate use, which had been approved to treat a specific type of malaria. However, numerous unapproved quinine sulfate drugs were marketed to relieve leg cramps. The adverse events included cardiac arrhythmia, renal failure and Myasthenia Gravis, a neurological disorder. The label of the one approved drug available at that time documented that quinine sulfate could cause potentially life-threatening cardiac arrhythmias and other serious adverse events and provided critical prescriber information to mitigate such risks. The label of many unapproved quinine sulfate drugs did not contain this safety information. After FDA acted to remove unapproved quinine sulfate from the market, three companies obtained FDA approval of the drug for the treatment of malaria, with a boxed warning regarding the life-threatening dangers associated with use of the drug for treatment of nocturnal leg cramps.
  • Single-ingredient oral colchicine products: From 1969 to 2007, FDA received 751 reports of adverse events associated with colchicine toxicity, including 169 deaths. A clinical trial revealed that a substantially lower dose of colchicine than had been the standard of care was just as effective and had significantly reduced unexpected side effects. Although an interaction with P-glycoprotein had been published in the medical literature, FDA continued to receive reports of deaths, which revealed that half of non-overdose colchicine fatalities were related to the concomitant use of colchicine and clarithromycin. This information resulted in important label changes to address these safety concerns on subsequent FDA approved versions of the drug.
  • Carbinoximine: From 1983 through 2006, FDA received nearly 100 reports of serious adverse events related to unapproved versions of carbinoxamine, a sedating antihistamine, frequently being prescribed for infants, including 21 deaths of children under two years of age. Following FDA action to remove unapproved products in 2006, FDA-approved carbinoxamine products are all marketed with a contraindication for children younger than two.
Back to Top