Peril or Promise: The Uncertainty of Off-label Prescriptions
Jennifer Wider, M.D.
Society for Women’s Health Research
November 22, 2004
The next time you have a prescription filled, make sure you’re taking the medication for the right reasons. The use of off-label prescriptions is on the rise. “Off label” refers to the use of an approved medication for any purposes other than what is listed on the drug’s labeling.
Off-label use is different from “expanded access” or a “special exemption” to use a drug, which allows patients access to experimental treatments not yet approved by the Food and Drug Administration.
Doctors frequently prescribe medications off label because there is evidence through practice or research that the drug may effectively treat a condition, even if the drug isn’t approved to treat that condition. This isn’t always the case, as drugs may be prescribed without strong evidence that they will work for a given condition.
Drugs tested and approved for treating seizures are being prescribed for a wide range of conditions from depression to weight loss. Anti-depressants are being used to treat premature ejaculation, restless leg syndrome and chronic pain syndromes.
Although it is legal for doctors to prescribe FDA approved medication for any reason they deem appropriate, it is illegal for pharmaceutical companies to market drugs for off-label purposes.
“Under current regulations, the FDA can only allow a drug label to list the specific conditions or indications for which the pharmaceutical company sought and received approval, based on extensive testing,” said Sherry Marts, Ph.D., vice president of scientific affairs for the Society for Women’s Health Research in Washington, D.C.
There may be sufficient evidence to support the use of a drug for multiple purposes, but the company that owns the drug may not sponsor the necessary research trials required for FDA approval, according to Marts, who was previously involved in the ethical review of clinical research.
Prozac, for example, was originally designed to treat clinical depression but later it was discovered to be effective for premenstrual dysphoric disorder. “Intermittent dosing worked and it worked rapidly,” Marts said. “And the company was willing to do the clinical trials to get FDA approval.” But that’s not true for all drugs which may have other indications that aren’t officially approved.
Pharmaceutical companies and doctors have always worked together. Drug representatives visit physician offices, medical conventions and hospitals touting the benefits of their company’s latest medication. They even offer free samples of specialized drugs to general practitioners, regardless of the physicians’ expertise in specific areas of medicine.
“Temptation to treat beyond one’s specialty in addition to economic pressure by insurance companies can put doctors in a tough situation,” Marts said.
Fen-Phen, a combination of the drugs fenfluramine and phentermine, was widely used off label as appetite suppressants for the short-term (a few weeks) management of obesity.
“The drug was never recommended for people who were simply overweight,” Marts said. “It was only indicated for people whose health was threatened by their obesity.” It was later discovered that the combination could cause heart valve problems and fenfluramine was pulled off the market.
Drugs prescribed for reasons other than what they were intended for can harm the patient and cost the manufacturing drug company millions of dollars. The drug maker Warner-Lambert agreed in May to pay over $400 million in fines and civil damages for illegally promoting Neurontin, an anti-seizure medication. The company falsely endorsed it for the treatment of other ailments ranging from headaches to attention deficit disorder, despite the lack of scientific evidence.
There are cases when a patient’s care requires the use of off-label treatments. Cancer care is a prime example, where treatments are rarely approved for general use against cancer. Instead, they are approved to treat specific stages of specific cancers.
A 1991 government study found that more than half of cancer patients received at least one drug for an off-label indication. Off-label use of drugs is widespread in cancer treatment for several reasons.
Some cancer drugs are effective against a variety of tumor types.
Cisplatin, produced as Platinol® by Bristol Myers Squibb, works to stop the uncontrolled growth of cancer cells by interrupting the copying of DNA in growing cells. Because uncontrolled cell growth is part of most cancers, cisplatin is often used in the treatment of thyroid and lung cancers. It is only approved to treat bladder, testicular and ovarian cancers.
The use of multiple drugs, which is typical in cancer chemotherapy treatment, is usually an off-label treatment. The FDA generally does not approve multidrug regimens because the potential number of combinations is vast.
Medical care is always evolving. When published research shows that a new treatment approach produces better outcomes for patients, many doctors will incorporate the findings into their practice, ahead of formal approval processes which can take years. These timely changes to care can benefit patients.
Whatever the situation, patients need to protect themselves by asking doctors about their prescriptions.
“Patients should write their questions down before walking into the doctor’s office,” Marts cautioned.
Before a doctor hands you a medication, seek answers to the following questions:
1. What is the name of the medication and what is it for?
2. What is your experience prescribing this?
3. What kind of side effects can I expect?
4. Is the medication safe to take with other drugs or dietary supplements that I may be taking?
5. Is there anything I should avoid while taking it?
6. What should I do if my symptoms do not go away?
© November 22, 2004 Society for Women's Health Research
