Last reviewed on November 10, 2015
Using drugs for indications not approved by the FDA or in species not listed on the label is a fine gray line many of us in the veterinary profession are uncomfortably forced to straddle.
That’s because way too many of our drugs are not economically significant enough for drug manufacturers to undertake the incredibly expensive approval process required to bring them to market for common animal species. And it’s even worse for the cavvys and cockatoos among us. I mean, who’s going to shell out hundreds of thousands of dollars for a medication that’ll only be applicable to rabbits...or reticulated pythons?
Then there’s the case of the many human and animal drugs made for just one problem, to be used at just one dose, and only for a certain amount of time or exclusively at certain specific intervals. Anything beyond this limited indication effectively means you’re using it “off label” or “extra label” (both terms mean essentially the same thing).
So if you choose to use the parasite-preventing Revolution, for example, to actually kill a parasite like ear mites (instead of prevent it), you’re engaging in an off label use of the product. Similarly, using Viagra to control blood pressure in humans (instead of for its erectile dysfunction indication) constitutes an off-label use of the drug, too.
According to the FDA, it’s OK to use products off label if there’s no other way of achieving the same effect...and if it conforms to the standard of care of your industry. Therefore, veterinarians who use the human drug Lipitor in dogs to reduce their cholesterol levels can do so––carefully, and with appropriately informed owners in tow (as all drug use should be).
But the FDA is careful about these innovative uses. And while it doesn’t want to stifle innovation at the level of basic research and clinical application, it certainly does NOT want docs using these drugs willy-nilly for whatever use, dose or frequency strikes his or her fancy.
Want a sense of the complexity of FDA policy on this? Here’s some explanatory testimony by the FDA’s William B. Schulz before a congressional committee back in ’96:
“Madam Chairman, I am here today to talk about uses that do not appear in a product's FDA-approved labeling and are not approved by the Agency. Such uses commonly are referred to as "off label," "unapproved," "unlabeled," or "extra-label" uses. The Food and Drug Administration (FDA)recognizes that, in certain circumstances, off label uses of approved products are appropriate, rational, and accepted medical practice. FDA knows that there are important off label uses of approved drugs. In this context, it is important that physicians have access to accurate information about drugs. But we also know that allowing the promotion of these kinds of uses can have negative public health consequences -- including exposing patients to unnecessary risks and destroying the incentive for companies to conduct the necessary research to demonstrate that products are safe and effective for these uses. Striking the proper balance between the need to regulate the promotion of unapproved uses for drugs and devices and the need for reliable scientific data and information on unapproved uses of approved products is a difficult and controversial challenge.”
In the last sentence here, the FDA refers to companies that would promote the off label use of their drugs, something the FDA finds wholly objectionable. The implication is that drug companies who engage in this practice do so by way of shirking their responsibility to appropriately investigate these uses and file proper FDA applications to expand their drug’s labeled use. Because, essentially, they’re using these off label patients as guinea pigs as they compile unpaid-for data on their drug’s cool new spinoff properties.
Now for the examples: Two things coincided this week to hammer home the point of off-label drug use and its pitfalls.
The first was all over the news: Pfizer was fined $3.2 Billion for using its drug representative army to promote off label uses for 13 of their drugs. Pfizer had engaged in this practice before, so I’d say the FDA was well within its rights to levy so high a fine. Yet because this sum represents only 3 weeks of revenues for a company Pfizer’s size, and because off label drug use is a huge consumer safety issue, there were plenty of complaints alleging that the fine was inadequate.
The next issue arose when I received a call from a North Carolina veterinarian unhappy over my use of Adequan in a cat. Said cat was one of my winter patients, a kitty with chronically intermittent bladder issues who responds to Adequan beautifully (here’s a post that discusses this indication). You can throw antibiotics and steroids her way all you want yet nothing alleviates her symptoms like Adequan does.
Problem is, Adequan’s use in this case is off label (it's not approved for use in cats). The NC vet did NOT want to relent on offering Adequan in his name––he required that I write a written prescription and a letter explaining why I was using this drug.
He also complained that the intramuscular injections were a big no no, implying that things in Florida must be a whole lot more lax than they are in North Carolina, since he would NEVER have allowed a client to administer IM injections of anything––much less an off label drug. ("Sub-Q is fine," I humbly agreed as I held my tongue.)
Not that I blame this veterinarian too much. In fact, I’d much prefer a careful soul such as him over the drug-happy kind of veterinarians we all know are out there. Nevertheless, I was taken aback by his lack of knowledge of this drug’s off label use in cats and by his unwillingness to employ ANY off label drugs in his practice unless they’d been in use for at least thirty-plus years.
So you know, this point of view is alive and well across the US. When it comes to steroids and antibiotics, anything goes, since many of these drugs have never been approved for use in dogs and cats. But when it comes to newer-fangled drugs, all bets are off. If there’s no veterinary version it’s a no-go. And if it’s only been approved for dogs you can forget it for your cat.
Never mind that veterinary specialists like oncologists, internists, cardiologists, dermatologists and exotics vets use drugs off label every single day. None of our chemotherapeutics are approved for pets. Not even diphenhydramine (Benadryl) is approved. The market is either too small to be worth anyone's while or the drugs have been commonly in use for so long that nobody cares anymore––so there’s no need for a drug company to go out of its way to make dogs, cats and conures any safer.
Then there’s this to consider: ARE your pets safer when these products are brought to market by way of a Pfizer or a Lilly? Or does it simply mean you’ll be paying more for the same drugs?
Consider the case of Prozac: It was expensive before it went off patent and was genericized into lowly fluoxetine. That’s when veterinarians discovered its profound benefits as an adjunct to behavior modification in highly stressed animals. In comes Lilly. It reorganizes the drug into a variety of non-human doses (8, 16, 32 and 62 mg instead of 10 and 20 mg), adds flavor, tests it for one indication (separation anxiety) and applies for FDA approval.
Now that Reconcile's been granted approval, veterinarians cannot use the off label human version without a darn good reason. Never mind that this is the exact same drug and that its off label use is all about whether we give a chewable or a capsule just a couple of milligrams different than the human formulation. It’s just marketing. But whenever I write a $4 fluoxetine script to help out a client with his finances, I know I do so at my own professional peril.
Same goes for meloxicam. Now that this drug has been approved for use in dogs as an oral liquid (as Metacam), there may be trouble in store for veterinarians who continue to write cheap scripts for the human generic (in a pill form).
Do I do it anyway? Sure I do. I just have to be extra careful to explain why I’m doing it and detail the client conversation in my medical records: “off label usage of X drug discussed.” Some veterinarians, like my NC colleague, will also ask another veterinarian to sign off on it and further distance themselves by asking the client to sign on a dotted line.
Despite my willingness to script out non-vet versions of chemically identical drugs, the truth is I believe drug companies deserve to be compensated for their investments, especially when they make drug use a safer prospect for my patients.
In fact, I still use Metacam (like water). I still carry Reconcile (and use it more than my other colleagues do). But when pet owners cannot afford these options (especially for very big dogs) or when they won’t take the medication in a pill or liquid (whichever the case may be), I’ll make adjustments to make things possible. And many veterinarians I know will do the same, despite the gloom and doom others among us may disseminate on the matter.
Is it uncomfortable? Does it add stress? Do I worry that one day my liberal use of off label drugs will come back to bite me in the butt? Of course I do. But it’ll never keep me from using drugs based solely on their labeling status––not while many pet health and welfare concerns are held captive by a drug paradigm that would otherwise limit my ability to care for animals to the best of my ability.