The Downside

Off-label use has negative attributes. First of all, it may be misleading to patients. They assume that any approved drug is effective and safe. They might not know that drugs are approved for a specific indication. Therefore, when prescribing off-label, physicians might consider informing patients about the lack of indication information and then evaluate together the risks and benefits of such a prescription. A legal problem for physicians could arise if they were faced with a malpractice suit, since off-label use often does not reflect a "standard of care" treatment. This leads to possible concern about the risk of prescribing off-label should a patient have serious side effects or a bad outcome from treatment.

Regarding reimbursement for off-label prescribing, some managed care organizations and other payers will not pay for off-label prescriptions, increasing the patient's out-of-pocket expense for medicines. Many insurance companies will not pay for an expensive drug that is used in a way that is not listed in the approved label; insurers claim that its use is "experimental" or "investigational."

Perhaps the FDA now takes the most progressive stance, allowing drug companies to give physicians journal articles that discuss off-label uses of products not yet approved by the FDA. This approach replaces the relevant provisions in the FDA 1997 Modernization Act (FDAMA), which expired in 2006. The new guidelines include provisions allowing dissemination of information if a drug company meets certain criteria. In this way, the FDA is making it easier for pharmaceutical companies to distribute more truthful, non-misleading, and objective information than had been possible in the past. It is assumed and hoped that this will benefit patients who might gain access to products which their physicians were previously unaware of, or reluctant to try.

Even with these protections and the additional latitude provided to drug companies and prescribing physicians, there are still some who object, claiming that there are insufficient protections for the patient. They argue that there should be a strict requirement compelling doctors to obtain informed consent from patients who are prescribed drugs for an off-label use just as they would before enrolling patients in a clinical research study.

Off-label prescribing of medications cannot automatically be criticized, as often this is the optimal therapy for some conditions. Unfortunately, there are numerous medical conditions and other morbidities where there are no approved, effective drug therapies available. Moreover, some very effective therapies have been discovered by serendipity in this way—an off-label use today may lead to tomorrow's effective and officially approved use of a drug. It is becoming possible for the practitioner to gain some legitimate and non-commercial information. The reference work "Facts and Comparisons" includes information about known off-label uses of many drugs. In addition, the US Pharmacopeia reference compendium lists at the end of a monograph information about any known off-label use of that drug.

As with many other situations where not all of the facts may be known, it seems that the wisest path is to approach the use of drugs for off-label conditions with great caution and as much knowledge as may be gained before the prescribing decision is arrived at.

Dr. Albert Wertheimer is director of the Center for Pharmaceutical Health Services Research and Professor, Temple University School of Pharmacy. He can be reached at albertw@temple.edu