How “off-label” drug prescriptions can fool patients – and pharmacists

Prescription drugs have an official label or package insert that lists its FDA-approved uses, but doctors are free to use almost any medication in ways that have not been approved. Such use is referred to as "off-label." One issue that arises is that pharmacists, and too often patients themselves, are kept in the dark about why they are getting the drug. That can lead to patients getting the wrong information from their pharmacist, which, in turn, can have troubling consequences.

Recently a patient with neck pain after an accident was given a prescription for Elavil (amitriptyline), a drug with FDA-approved labeling for treatment of depression. When the patient picked up his prescription, the pharmacist gave him a drug information leaflet that mentioned, among other things, that it was used to treat depression. The leaflet did not mention that the drug might also be used to treat what's called "neuropathic" pain, a condition where a nerve is injured or malfunctioning, and sends pain messages to your brain. The patient called the pharmacist, who reinforced, incorrectly as it turned out, that the drug was used for depression.

This isn't the first time this happened with this drug. In a similar case, an elderly woman also was prescribed amitriptyline to treat neuropathic pain and again not told that the drug was being used to treat this condition. Upon learning that the drug was used for depression, she became angry with her physician for believing her pain was "all in her head" and refused to take the medication.

Because their doctors never communicated the intended purpose of the Elavil prescriptions to these patients or their pharmacists (treatment of neuropathic pain), the patient patients were unnecessarily quite angry with their doctors for "misdiagnosing" their condition, each thinking their doctor didn't believe they were actually in pain. Yet although not an FDA-approved use, neuropathic pain is a well-accepted use for Elavil and other drugs in its class (called tricyclic antidepressants).

Among other problems, not knowing the purpose of medications also can contribute to diagnostic errors. A 2003 BMJ article  described two patients who were prescribed Tegretol (carbamazepine), another drug used off-label for neuropathic pain. However, the patients were never made to understand the medication's intended use for pain. Tegretol is FDA-approved as an anticonvulsant for epilepsy. After developing blackouts, the patients and their treating physicians (who had not prescribed the Tegretol) inferred from the drug therapy that their patients must have had epilepsy and seizures. That led to both patients undergoing unnecessary diagnostic procedures and treatment for the seizures, rather than identifying the problem for what it was - a drug-related adverse event.

Doctors often prescribe medications off-label, based on published clinical studies or reports and even their own experience. Off-label use is legal and can certainly be beneficial. It's done because not all important uses for a drug have been well vetted and presented to FDA for approval, most often because of the enormous expense a drug company must bear to sponsor the required research and the FDA approval process. Still, in their excellent book, Knowing your medications; A guide to becoming an informed patient (Potata, Inc.), drug safety colleagues Curt and Bengt Furberg and Larry Sasich make the important point that promotion of off-label uses by a drug's manufacturer is against the law since there is no validated evidence that the drug is safe and effective for the specific off label use. Benefits and harm can be different depending on what is being treated.

Be on your toes about off-label uses of medications because we continue to read about large fines that drug companies were required to pay for off-label promotion. While the government is being aggressive in pursuing manufacturers who promote off-label, often the profits exceed the fines, even though they may go into the billions of dollars. Also, for very expensive drugs, even for cancer patients, some insurance companies or other payers may not agree to cover costs.

Prescribers should always clarify the purpose of each medication with patients and include it on prescriptions,

Especially if the drug has multiple uses or is being used "off-label." Always ask your doctor what drugs are being used off-label and be sure you are closely monitored for any unusual side effects.

For more on ISMP's consumer website, go www.consumermedsafety.org.