Acknowledge the Complex Medical and Legal Issues Surrounding Off-Label Drug Use

Acknowledge the Complex Medical and Legal Issues Surrounding Off-Label Drug Use

Angela M. Pennell MD

Imagine this scene: Your healthy, 5-year-old patient has just emerged from anesthesia after a routine, 30-minute case for PE tube placement. She is ventilating spontaneously and her vital signs are stable. As you leave the operating room (OR), she becomes agitated, screaming and thrashing on the stretcher and inconsolable. Pondering your options for treating her emergence delirium, you acknowledge that she does not have an intravenous (IV) line. Quickly, you administer 2 mcg/kg of intranasal clonidine. She becomes calm and quiet and you are thankful she is no longer a risk to herself. Her parents are reassured, the postanesthesia care unit (PACU) nurses are able to carefor their new patient efficiently, and you move on to your next case without interruption. This was a successful and safe intervention, wasn’t it? Perhaps so, but intranasal clonidine use is not described in the U.S. Food and Drug Administration (FDA) package insert.

The practice of anesthesiology reflects a mastery of pharmacology. Not only is the proper indication for and administration of a particular drug important to the anesthesia provider, but also the ability to co-administer agents or even to use them in novel ways. The most responsible and safest approach to this practice is to acknowledge drug labels created by the FDA and then strive to apply those guidelines to clinical practice. If a drug is used beyond those conditions described on its label, it is considered off-label.

The FDA regulates many aspects of drug development, research, safety, marketing, and labeling. The drug label is a summary of data collected by clinical trials. Therefore, in order to achieve approval for specific uses of a drug there must be evidence-based data to support it. Obviously, we cannot anticipate every detail of our patient population. So, based on medical literature, drugs are frequently used beyond the specific guidelines listed in the drug label for dose, route, indication, regimen, or patient population. How common is this practice? Sources site up to 23% of prescriptions being written for off-label use. This trend is not necessarily harmful, but, rather, reflects a lack of well-controlled study data held by the FDA (the study has not been done or there is no financial incentive to develop new indications,
e.g., isobaric spinal bupivacaine). Further, if there is a known adverse effect of an off-label drug use, it will be listed in the Contraindications, Warnings, or Precautions section of the label.

According to the FDA, “once a product has been approved for marketing, a physician may prescribe it for uses in treatment regimens or patient populations that are not included in approved labeling. Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic interventions.” It is important to realize that the FDA does not seek to restrict a physician’s decision to use a drug off-label and the Physicians’ Desk Reference (PDR) also acknowledges this use. Interestingly, the publisher of the PDR, Medical Economics, also publishes an “off-label treatment guide.” So, there is acknowledgement that this use has an important place in patient care. Currently in the United States, the physician has no ethical or legal obligation to educate the patient on FDA regulatory status when a drug is used. However, it is the physician’s responsibility to be aware of details in the drug label, including pharmacology, toxicology, and chemistry (buffers, preservatives, antioxidants, and incompatibility with other drugs).

Anesthesiologists must also consider the unfortunate litigious climate of medicine. Drug manufacturers, the FDA, and the PDR all recognize the clinically observed safe and effective uses of a variety of medicines although they may not be supported by well-controlled, evidence-based data. However, courts and judges may have the ultimate authority over a physician’s ability to practice off-label pharmacology and the liability for doing so (e.g., gabapentin and suicide risk). To be found liable for off-label drug use, the patient must prove that the anesthesiologist committed a breach of duty of care, that the breach resulted from a failure to reach the standard of care required by the law, and that the breach of duty resulted in injury. Based on the importance and well-recognized practice of off-label drug use per a physician’s discretion, for a drug manufacturer to assert that it warned against unapproved uses is disingenuous. However, harm incurred to a patient related to an off-label use of a medication may ultimately be the prescriber’s responsibility.

In general, there is a growing feeling that off-label drug use is the newly discovered gold mine of malpractice attorneys. The “learned intermediary” doctrine used by pharmaceutical manufacturers to protect them from liability asserts that they have provided the physician with warnings about a drug via the drug label. Hence, the physician now has the duty to warn the patient about that drug’s hazards. Of course, this issue is really very complex. Ultimately, the FDA package insert must list the side effect of which the patient complains and there must be a way to prove that the patient was not adequately warned or was misled by the physician about those side effects. And,
in countries such as England, cases are being decided in favor of patients who claim that they were given inadequate information about a drug and, therefore, did not give informed consent. In situations in which there are alternative, FDA-approved medications to a drug being used off-label and purportedly resulting in harm, it might be difficult to convince a jury that the decision of the physician was sound. Thus, in England, physicians must now obtain informed consent for prescribed medicines, especially those used off-label. This includes risks and benefits, information about “approved” alternatives, education about the meaning of off-label drug use, and the lack of testing existing for that use. In England, to use a drug off-label is then justified only if there is no approved alternative and not because the use is more convenient or less costly.


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Jul 1, 2016 | Posted by in ANESTHESIA | Comments Off on Acknowledge the Complex Medical and Legal Issues Surrounding Off-Label Drug Use
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