My readers have asked me to write about off-label prescriptions and to explain what that is all about.
So here's the deal.
An “off-label drug” is simply a drug used for a condition or in a manner not appearing on the FDA approved label.
The American Medical Association reported in 1995 that approximately half of all prescriptions were written for off-label uses and its hardly less today. Moreover, the General Accounting Office (GAO) has testified that 90 percent of cancer drug use, 80 percent of pediatric use, and 80-90 percent of drugs used to treat rare diseases are prescribed off-label.
Perhaps the best known example is aspirin.
For years, physicians prescribed aspirin to reduce the risk of heart attacks. However, the FDA did not approve such usage until 1998.
A less celebrated example is Fen-Phen. Both fenfluramine (“Fen”) and phentermine (“Phen”) were approved by the FDA for weight loss. However, doctors ignored fenfluramine’s labeling by having some patients use the medicine for more than a year when it was only labeled for duration of a “few weeks,” and by combining the two drugs even though neither label discussed using the drugs in tandem. Many patients suffered heart valve damage as a result.
We can identify three kinds of off-label activities – off-label use, off-label prescription, and off-label marketing.
Off-label use occurs when a consumer uses a drug in a manner inconsistent with its label. This entails changing the dosage amount or frequency, combining the drug with others, using the medicine to treat an unapproved condition, or giving the medicine to someone for whom it was not prescribed. It is nearly impossible to monitor for off-label use and congress has never attempted to outlaw its practice.
Off-label prescription, in contrast, occurs when a doctor prescribes a drug in a manner inconsistent with its FDA approved label. For example, a physician may prescribe a drug for a disease other than the ones listed on the label, in an unapproved dosage, for unapproved duration or in an unapproved combination with other medicines. The doctor may also prescribe the drug to groups, such as children or pregnant women, for whom the FDA has not approved the drugs usage. Congress has long deferred to a physician’s medical judgment to prescribe medicine as they wish..
The final category, off-label promotion, is regulated by the FDA. Manufacturers cannot market their products “for purposes, to users, in dosages, or in combinations other than FDA-approved ones." While recent legislation has created certain exceptions to this blanket prohibition, the promotion of drugs for off-label uses remains highly regulated and has resulted in the drug indusry paying billions of dollars in fines.
It must be stressed that there is no doubt as to the legality of off-label use or prescription for most drugs. (There are a few exceptions to this rule, such as growth hormone, where distribution for off-label use is a criminal offense.) The illegality concerns the appropriateness of prescription drug manufacturers promoting off-label aspects of their product.
The GAO reports that off-label use often represents “state-of-the-art” treatment, and the FDA asserts that “good medical practice and patient interests require that physicians use commercially available drugs, devices, and biologics, according to their best knowledge and judgment.”
Furthermore, one should be careful not to interpret the phrase “unapproved use” to mean “disapproved use.” The FDA does not take a position on the safety of an off-label use; rather, the agency leaves that determination to the individual doctor as part of his or her practice of medicine.
This position has been stated repeatedly.
For example, in a 1972 pronouncement, the FDA declared that once a drug has left a manufacturer’s warehouse a “physician may, as part of the practice of medicine lawfully prescribe a different dosage for his patient, or may otherwise vary the conditions of use from those approved in the package insert. Ten years later, the FDA again stressed that off-label use is accepted medical practice, and FDA approved labeling should be used for informational purposes only. Physicians have embraced this freedom and off-label drug use has become an accepted method of treatment for many diseases.
1. Beck, James M. and Azari, Elizabeth D. 1998. FDA, Off-Label Drug Use, and Informed Consent: Debunking Myths and Misconceptions. 53 Food, Drug, Cosmetic Law Journal 71.
2. Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration 2003. Oncology Tools: A Short Tour. www.fda.gov (accessed June 15, 2004). www.wada-ama.org
3. Harris, Gardener. 2004. Pfizer to Pay $430 Million Over Promoting Drug to Doctors. New York Times, May 14, at C5.
4. O'Reilly, James O. and Dalal, Amy 2003. Off-Label or Out of Bounds? Prescriber and Marketer Liability for Unapproved Uses of FDA-Approved Drugs. 12 Ann. Health L. 295-324.
5. Salbu, Steven R. 1999. The FDA and Public Access to New Drugs: Appropriate Levels of Scrutiny in the Wake of HIV, AIDS, and the Diet Drug Debacle. 79 Boston Univ. L. Rev. 93 (1999).
6. Tabarrok, Alexander T. 2000. Assessing the FDA Via the Anomaly of Off-Label Drug Prescribing. The Independent Review V(1):25-53.
7. U.S. Food and Drug Administration 2000. Decision in Washington Legal Foundation v. Henney. 65 Fed. Reg. 14286 (March 16).
8. 1972: Legal Status of Approved Labeling for Prescription Drugs; Prescribing for Uses Unapproved by the Food and Drug Administration, 37 Fed. Reg. 16503, 16504 (July 30).