Treatment Plan

Is Off-Label Prescribing Going to Get Easier?

BY LEO SEMES, OD, FAAO

Much has been in the news recently about off-label use of FDA-approved medications. Several large pharmaceutical manufacturers have been accused of promoting off-label uses for their products. At the end of last year, Amgen settled for $762 million (Pollack and Secret, 2012) for off-label promotion of an anemia drug. In July 2012, Glaxo plead guilty and was assessed $3 billion for off-label promotion as well as for failure to report safety issues (Department of Justice, 2012).

Let’s take a closer look at how off-label uses are applied.

The FDA’s Process

First, when the FDA approves a drug, it mandates that the manufacturer specify in the package insert certain parameters of a medication’s use (U.S. Department of Health and Human Services, 2013). These include:

• Indication(s) for the use of the medication

• Dosage forms and strengths

• Dosage and administration; i.e., treatment regimen, including:

° Number of times that a medication is taken per day

° Time course for the medication: when to start and stop treatment, patient population (e.g., adults, children, etc.)

It is useful to become familiar with the indicated uses of the medications that we prescribe. Obviously, this helps us comply with federal regulations and state laws. In addition, some patients may bring items to our attention that have been enumerated in those package inserts. These are not only available with the dispensed medication, but are also accessible online.

We all make the decision for off-label application of medications. These may include something as simple as a different dosing schedule to enhance compliance (for example, reducing a medication’s dosage from the indicated three times per day dosing to two times). Other reasons may include cost, or the belief that two instillations are nearly as good as three. To choose this or similar strategies, there needs to be substantial evidence for the alternative dosing or indication.

It’s essential that we discuss off-label strategies with patients and that we document alternative strategies or treatment indications in patients’ records.

Back to Court

Off-label marketing has recently been reviewed in the courts. In their decision in U.S. v. Caronia (U.S. Second Circuit Court of Appeals, 2010), a three-judge panel overturned the conviction of a drug company representative and his firm for off-label marketing. The issue was not clinical, but the court invoked the First Amendment, contending that off-label marketing is protected free speech. Does this give any prescriber carte blanche? Unlikely. There could be appeals to the Supreme Court, but the FDA has indicated that it is unlikely to pursue this route.

This decision, coupled with two similar cases, has significant implications that are already being felt in the healthcare industry (Boumil, 2013). Essentially, these opinions indicate that the courts apparently feel that the FDA regulations, while allowing prescribing for off-label uses, prohibit a free flow of information that infringes on the First Amendment.

Will it be the courts, or the FDA, that defines the boundaries for our prescribing and manufacturers’ advertising? Will this broaden off-label indications? Not likely, as these have to be substantiated by clinical evidence. Off-label prescribing will probably not be influenced by these decisions. But the issue of off-label marketing is one that will likely be resolved later rather than sooner.

Stay tuned, and proceed with caution. CLS

Dr. Semes is a professor of optometry at the UAB School of Optometry. He is a stock shareholder of H.P.O. and is a consultant or advisor to Zeiss, B+L, Arctic Dx, Merck, Sucampo, Alcon, and Allergan.