March 23, 2020 1:27PM

Coronavirus, Chloroquine, and “Off‐​label” Use

At a Coronavirus Task Force briefing last week, President Trump incorrectly told the press that the antimalarial drug chloroquine had already gone through the Food and Drug Administration’s approval process for the treatment of COVID-19 infection: “They’ve gone through the approval process, it’s been approved and they did it, they took it down from many, many months to immediate.” He was later corrected by the FDA Commissioner, who said the approval process had not and will not be completed until controlled clinical trials have convinced the agency.

Many people might therefore conclude that doctors are not legally permitted to prescribe chloroquine, or its analog hydroxychloroquine, to treat COVID-19 infections. In fact, doctors around the globe, including the U.S., are using these and other drugs to treat their patients, and reporting on their findings in the peer‐​reviewed medical literature.

French medical researchers reported on the chloroquine’s potential based upon their experience with a small group of patients in the March issue of the International Journal of Antimicrobial Agents. Chinese medical researchers reported similar encouraging results in early February. Researchers at the University of Washington in Seattle are using chloroquine to treat their COVID-19 patients, with one of its research associates calling the results thus far “very promising.” And a report in today’s Wall Street Journal by a practicing physician and the director of the Division of Infectious Disease at the University of Kansas Medical Center also touts the drug’s potential.

The use of chloroquine, hydroxychloroquine, and other drugs (such as azithromycin and antiviral drugs used to treat HIV) to treat COVID-19 are examples of “off‐​label” drug prescribing.

Prior to 1962, drug makers were required to convince the FDA their product was safe to consume and met the FDA’s criteria for providing product information, use, and dosage on their labels. But the 1962 Kefauver‐​Harris Amendments to the Food Drug and Cosmetic Act of 1938 added the additional burden of proving the drug’s efficacy in treating the condition for which it was developed.

Efficacy requirements add years to the approval process. Ironically, once a drug is thus approved for the treatment of the condition for which it was initially intended, the FDA has no restrictions on using the drug in any other setting. Using it to treat a condition for which it was not initially approved is called “off‐​label,” because the label is only allowed to state the condition for which its use was FDA‐​approved.

It is reasonable to wonder why, after doctors wait several years to get permission from the FDA to treat their patients with a drug for condition “A,” the FDA in principle trusts doctors to use their clinical judgment, based on their knowledge and experience, to treat conditions “B thru Z.” Why not skip the efficacy component of the approval process and speed things up? Alas, a great many patients suffer or even die waiting for the chance to see if a drug that may be helping patients in other countries can be used by them—a problem called “drug lag.”

Clinicians use drugs “off label” very frequently. In fact, according to the Agency for Healthcare Research and Quality, “one in five prescriptions written today are for off‐​label use.” An example of off‐​label use in my specialty of general surgery that immediately comes to mind is the antibiotic erythromycin to treat paralyzed intrinsic muscles of the stomach, a condition called gastric atony.

Many years often pass before clinical trials convince the FDA to update its approved use of a drug to include what had been an off‐​label use. Aspirin had been used off‐​label to prevent recurrent stroke or heart attack for many years before the FDA approved it for that use.

Most of what clinicians read in medical journals or observe at scientific conferences deal with the efficacy and comparative effectiveness of various medications or procedures in the treatment of health conditions.

It may indeed turn out that the FDA eventually approves chloroquine, hydroxychloroquine, and other drugs currently used off‐​label for the treatment of coronavirus and other viral infections. That could still be quite a while off. In the meantime, it is important for people to know that clinicians are not prohibited from using these drugs now. If a life‐​threatening situation develops, they can discuss using one or more of them with their health care provider.