Drug Profile

This old three-drug combination of isometheptene, dichloralphenazone, and acetaminophen was approved by the FDA before 1962, when amendments to the Food, Drug, and Cosmetic Act were passed that required manufacturers to show “substantial evidence” that their products would do what they claimed. In other words, that their drugs were effective.

The 1962 law required the FDA to review the effectiveness for all prescription drugs approved for marketing between 1938, when safety first became a standard for marketing, and 1962. The FDA entered into a contract with the National Academy of Sciences–National Research Council (NAS-NRC) in 1966 to fulfill its legal requirement. Drug companies were asked to submit data to the NAS-NRC to support their claims of effectiveness.[1] This process was known as the Drug Efficacy Study Implementation (DESI) program.

The FDA was supposed to begin marketing withdrawal procedures if substantial evidence of effectiveness was not presented. Unfortunately, the FDA failed to do its job, and 38 years after the DESI program began, numerous, less-than-effective drugs remain on the market today. The combination of isometheptene, dichloralphenazone, and acetaminophen is one of them.

The FDA-approved professional product labeling or package insert for the drug is required to display the following cryptic statement, in a box:[2]

The NAS-NRC translation of “possibly” effective is that substantial research is needed to substantiate effectiveness. According to one former NAS-NRC scientific panelist, “this designation means that in the best judgment of the panel members, if appropriate controlled studies were to be done, the result would be negative.”

In August 2001, the Drug Enforcement Administration reclassified Midrin as a controlled substance because the ingredient dichloralphenazone breaks down to chloral hydrate (NOCTEC), a very old sleeping medication that is a controlled substance.[3]