Greater vigilance needed for unapproved agents; reduce demand for these drugs by reporting adverse events

December 1, 2010

Removal of marketed unapproved drugs (MUDs), such as that with oral colchicine, is part of FDA's Unapproved Drugs Initiative (launched in 2006).

Key Points

Removal of marketed unapproved drugs (MUDs), such as that with oral colchicine, is part of FDA's Unapproved Drugs Initiative (launched in 2006).

Single-ingredient oral colchicine products have been associated with adverse drug events (ADEs), including fatalities, and were never FDA approved.

MUDs are agents that have been marketed illegally, without approved New Drug Applications (NDAs) or Abbreviated NDAs (ANDAs). Most MUDs were older ingredients marketed in the United States prior to 1962, when the Kefauver-Harris Amendment to the Food, Drug and Cosmetic Act began requiring effectiveness, as well as safety data, in order to gain FDA approval. However, many of these ingredients were recently reintroduced, according to research presented during the Academy of Managed Care Pharmacy's 2010 Educational Conference in St. Louis.

Manolakis said, however, that not all unapproved drugs will require removal from the market; some serve important medical needs and should be submitted to FDA for review and approval to confirm that use is appropriate, and that the products: are documented to be safe and effective as marketed; include dosing recommendations and target patient populations that are grounded in scientific evidence; are labeled with necessary warnings; are manufactured according to modern, high-quality standards; and are named and labeled to avoid potential mix-ups and medication errors.

"As pharmacists working in different health-systems, we can help to reduce demand of these agents by encouraging their manufacturers to obtain FDA approval, require that only FDA-approved drugs be included on our formularies, and report ADEs," Manolakis said. "We also need to educate others that these agents are not safe and not FDA-approved."

These agents have been able to remain "used and available" because of misperceptions about grandfathering and approval laws, automatic inclusion of core drug groups on formularies, as well as providing blanket coverage of "all generics" and/or repackaged products. A serious implication of their use is that they are a safety risk to patients.

In the case of colchicine, one manufacturer has obtained FDA approval, therefore FDA has required that all other companies halt manufacturing and distribution of unapproved colchicine. Another serious implication of their use is that they are subject to fraud potential under Centers for Medicare and Medicaid Services (CMS) if used to treat Medicare Part D patients. Most unapproved drugs do not meet the definition of a covered Part D drug.