Off-label drugs offer patients expanded treatment options

During the early ’80s, Dr. Joe Hardy was stationed in South Dakota with the Air Force and treated a patient who suffered from Raynaud’s disease, in which exposure to cold causes numbness in the hands and feet as a result of arteries clamping down and cutting off circulation.

Hardy knew of an alpha blocker — a type of medication usually prescribed to treat high blood pressure — that would block contraction of the arteries, and wondered if it could offer his patient relief.

Hardy had no studies to work with. As far as he knew, the drug never had been studied for that purpose and, indeed, wasn’t approved for that purpose. But, given how the drug worked, it seemed logical. Its effects and side effects were well-known. And it was a drug that was both legal and safe.

So, Hardy told the woman about the drug. He explained to her that it wasn’t approved for the purpose for which he was prescribing it.

And, Hardy says, “it changed her life.”

“Now, she’s in South Dakota, and she can use this medicine that prevented her fingers from feeling cold and painful, like frostbite,” he says.

And, Hardy continues, “maybe six months later, there was a letter in the New England Journal of Medicine (from another physician) who did exactly what I did.”

This scenario — using a prescription drug to treat a condition totally different from the one it has been approved for — isn’t uncommon in medicine, and there’s nothing illegal, ethically wrong or shady about it. Rather, physicians say, so-called off-label prescribing provides doctors, and their patients, with treatment options that wouldn’t otherwise exist, particularly if drugs specifically approved for that purpose haven’t worked.

Mark Decerbo, a doctor of pharmacy and associate professor of pharmacy practice at Roseman University of Health Sciences College of Pharmacy in Henderson, says estimates are that maybe one out of every five or so prescriptions for drugs in this country are being used for nonapproved indications, aka off-label use.

Hardy, a family practice physician and associate professor at Touro University Nevada College of Osteopathic Medicine, says it would be unusual to find a family physician who doesn’t prescribe drugs for off-label use “on a regular basis.”

The U.S. Food and Drug Administration’s approval to market a drug comes only after its manufacturer has spent millions of dollars and years of time in research and development and clinical trials to ensure that the drug is both effective and safe.

Then, when FDA approval does come, Hardy says, it approves the drug to be used for a given circumstance, for a given disease, in a given dose for a given time period, and with expected indications and contraindications.

So, Hardy says, any new drug hits the market with a very tight description for what the drug has proven to be useful for, and knowing its effects and side effects.

However, physicians and other medical professionals who are licensed to prescribe drugs are permitted to prescribe an FDA-approved drug for any purpose and for any medical condition for which they believe it will be safe and effective.

That’s important — and potentially beneficial to patients — because it may be that only after a drug is approved and hits the market that it might be found to “have some unintended consequences” that may be good for a patient, says Dr. Thomas Hunt, a Las Vegas family practice physician and associate professor of family and community medicine at the University of Nevada School of Medicine.

The discovery may come from private researchers or organizations devoted to researching specific diseases, Decerbo says. Or, it may be found by individual practitioners who, based on an examination of a drug’s chemistry, effects and side effects, suspect that it might be useful for treating other conditions as well.

“From a scientific standpoint, if you understand how a drug works, you’ll be able to say, ‘Well, if it works on this, then wouldn’t it be reasonable to think it will help this other thing?’ ” Hardy says.

Researchers and physicians then may spread the word through journal articles, studies they conduct and publish, or through word-of-mouth at professional conferences and among colleagues.

However, even as all of this ad hoc research is taking place, drug companies remain bound to marketing their drugs only for approved purposes.

“Once upon a time, years ago, there was a wink-wink, nod-nod type of approach” in the way drug companies notified doctors of off-label uses, Decerbo says. “But the FDA started coming down with heavy fines for pharmaceutical companies that do that.”

Even if a drug is found to have off-label uses, pharmaceutical companies usually won’t choose to undertake a new round of long and expensive clinical testing to have the off-label use formally approved by the FDA.

“I can’t speak for drug or pharmaceutical companies,” Hunt says, “but if I have a blockbuster drug that’s already selling like hotcakes, does it make financial sense to go back and do more studies to get another FDA authorization when, in fact, it’s all out there?”

And, Hunt says, “there’s the flip side, which is more common: You have a generic drug out there that’s cheap as dirt, so nobody will do any studies on them, but we know they work for more than just what it’s approved for.”

Still, that’s not always the case. For instance, Hunt says, “there’s a medication called Wellbutrin, an antidepressant, and what they found is, patients who are on it, many of them quit smoking.”

So, he says, the manufacturer went back and did studies and got approval to sell the drug for smoking cessation.

“That’s the exception as opposed to the rule,” he says. “They put a different name (Zyban) on it, and sell this same drug under two names, one for depression and one for smoking cessation.”

One type of drug commonly used for off-label purposes are antidepressants. For example, Hunt says, one possible side effect of antidepressants is prolonging the time it takes a man to ejaculate.

“So,” he says, “if you have a guy who comes in and has premature ejaculation as a concern or worry, this may be a great use off-label use of drugs.”

Reducing anxiety is a common off-label use for beta blockers, which are normally prescribed to treat hypertension.

“If you look at how they work, basically they block the beta receptors which respond to adrenaline,” Hunt says.

For drugs that have been used off-label to prevent migraines, “the list is as long as your arm,” Hunt says. “Many of them are generic and, I’m sure, not approved for migraine prophylaxis, but useful.”

Similarly, Hardy says some antidepressants and anti-seizure medications are prescribed off-label — and at much lower doses than they would be for treating depression — to treat chronic neuralgia, or nerve pain.

But, for all the good they can do, physicians don’t prescribe off-label medications — or, really, any other medication — lightly.

“I don’t want you to think this is a bunch of cowboys out there doing this by the seat of their pants,” Hardy says. “Because we talk to each other. We go to conferences. We have papers that people say, ‘Guess what this did?’ So it’s not like a bunch of people all by themselves doing this.

“I guess my story about the lady with Raynaud’s is somewhat unique in that it was just an isolated doctor, thinking in his office. Most of the things (used) off-label, they’re regularly talked about in medical meetings. It’s not like we’re trying to hide this from people. I think that the important thing is, these are safe medicines and we know how to respect them.”

As with any medication, good communication between physician and patient is an essential part of the prescribing process. In prescribing a drug for off-label use, the doctor-patient conversation, Hunt says, might go along the lines of: “You know, we don’t really have a very good medication for this. Nothing seems to be working. Here’s a medication that’s not used for this, but it may help. Here are some side effects. Are you interested in trying it?”

“People have to be active in their health care and have to know what’s going on and why a medicine is prescribed,” he says, “and it’s incumbent on both physician and patient to have that conversation.”

Also, the use of any drug involves balancing the benefit it can offer with the side effects it might cause. But, Hunt says, “most of the things we’re talking about are common drugs that are out there and that we have been using for decades. We know what they do.”

Another potential advantage to the patient is that some of the more commonly used off-label drugs are inexpensive. However, Hardy notes that it’s wise to check with your pharmacy to see if your drug plan covers drugs used for off-label purposes and what conditions might have to be met first.

In the end, a drug’s use for on- or off-label purposes is less important than the benefit it may offer a patient, Decerbo says.

“The way physicians work is, they know the evidence and they know the practice guidelines from all of the authoritative professional organizations, and that’s really what’s more important: Will this help patients live longer and improve their quality of life? What is of lesser importance is, ‘Is this drug specifically (approved) for this specific indication?’

“So, on the whole, more patients benefit from this than not.”

Contact reporter John Przybys at jprzybys@reviewjournal.com or 702-383-0280.