NEWS
Veterinary Topics: Compounding a problem
Posted: Saturday, May 29, 2004
Chance to save money and still treat horses is helping fuel the pirated drug trade
WHEN WE mention illegal drugs, stimulants and narcotics leap to mind. We think about the misuse of prescription pain-control medication or steroid abuse. We probably do not think about routine equine medications and products that are probably in our tack trunks. This is because the exact rules and regulations governing many common products that veterinarians, trainers, and owners use are confusing, complicated, and many times simply overlooked.
There has been a recent attempt to increase the general knowledge of these rules and laws. Veterinarians, pharmacists, and clients using these drugs and products are being encouraged to find out where they stand and to take appropriate steps to become compliant before they are forced to.
Much of the current problem with equine drugs comes from the fact that for a number of reasons, many companies stop producing various medications in use for horses.
"[The withdrawal of previously produced equine medications] has left us in a bit of a lurch without a place to go to provide our clients and our patients with medications that we need," said Rick Mitchell, D.V.M., of Newtown, Connecticut, speaking at a round table discussion on the issue in New York in August 2003. "In those cases, we will go to the compounders for medications."
The compounders that Mitchell mentions are various pharmacies that will produce specific drugs and medications upon request from veterinarians. These companies are legal and perform an important service to equine clients.
Joe Bertone, D.V.M., a professor of equine medicine and former medical officer at the United States Food and Drug Administration, spoke at the same round-table discussion.
"There are several reasons why drugs are removed from the marketplace," Bertone said. "These include poor financial viability, manufacture line retooling, or loss of quality chemicals for manufacture. In these and other cases, the compounding pharmacy is essential."
The correct process is for a veterinarian to make a prescription or request to a pharmacy for a specific need for a specific animal. Problems start to occur when this process is not followed.
If veterinarians order compounded drugs without having specific needs for those drugs, they could be illegally distributing those drugs. If the drugs are pirated copies of legally available drugs, then the practice is illegal. If the drugs in question are produced from bulk materials, they may be illegal as well since the FDA controls the materials used to make medications.
"No active ingredients found in FDA-approved medications are allowed into the United States," Bertone said, "so when you purchase omeprazole [the drug in GastroGard used to treat stomach ulcers] from drug pirates who pose as compounding pharmacists, the omeprazole at some point was smuggled into the United States."
Concern with pirating
The case of omeprazole brings up many issues that are causing the current concern surrounding compounding. Drug companies in the U.S. are required to spend a great deal of time and money to get a medication approved for use. An FDA-approved factory to be used to produce an injectable medication can cost nearly $10-million to construct. The entire approval process for a new drug can take roughly five to eight years. The company must prove the product's safety. It must show that the formulation (active ingredients, stabilizers, and fillers in the specific form to be administered) works, can be made consistently, and has stability. There also are strict regulations regarding adverse reactions.
These safeguards are in place to protect you and your horse, and they represent a substantial commitment on the part of the drug company. If compounding companies produce a pirated copy of an FDA-approved drug once it has been released to the marketplace, then there is little reason for drug companies to conduct the research and development required to produce new drugs. There is no way for these companies to recover their investment, and some veterinarians fear this will lead to fewer new drugs. Pirated omeprazole is often sold more cheaply than the FDA-approved product, and it is easy to see why. Pirated compounders have no need to recover money used to develop the product.
Because pirated drugs and medications often are made from illegal bulk ingredients, the safety, effectiveness, and freedom from adverse reactions cannot be guaranteed. Omeprazole again provides a good example. If you are prescribed or purchase pirated omeprazole rather than GastroGard, you have no way of telling what is in the product you are using. Mitchell related details of a study he had conducted looking at equine gastric ulcers.
"It's amazing to me the number of horses that were on generic omeprazole, as it was called, that had just rampant equine gastric ulcer syndrome," Mitchell said. "The people were frustrated because they were saying well, that GastroGard stuff doesn't work."
In fact, many so-called generic products that were checked did not contain the correct amount, formulation, or combination of ingredients. The drug pergolide (Permax), used to treat Cushing's disease, is another example. The exact dosage is individual, as is the rate of response to the drug. Because Permax is such an expensive drug, many clients try to find cheaper sources of the medication. Compounding pharmacies now offer Permax in liquid form (the FDA-approved drug is a pill) at different concentrations. Clients have used these pirated forms of Permax and found their horses did not respond or needed higher doses to respond. Were these horses truly not responsive or did the compounded drugs fail to meet FDA specifications?
The clenbuterol drug Ventipulmin falls into the same category. Less expensive renegade Ventipulmin offered through compounding pharmacies was found to be a sham drug. At the compounding round table, Bob Stenbom, D.V.M., an equine professional service manager for Boehringer Ingelheim, the manufacturer of Ventipulmin, related his company's evaluation of these pirated products.
"The analytical results we looked at were all over the board and none [of the pirated Ventipulmin] that we looked at met any of the specifications for the FDA-approved product," Stenbom said.
While lack of efficacy is important, the threat of adverse reactions is especially serious. Mitchell called this aspect of pirated drugs "a potential time bomb for a lot of practitioners." Unknown ingredients or additives in especially sensitive drugs even could be fatal in some situations. Reports of serious reactions to drugs used in joint injections have been made and are part of the body of information that has pushed the compounding issue to the forefront.
Incorrect use
There are many other areas of concern regarding compounded drugs. The law states that compounded drugs cannot be distributed to a third party that adds a markup in price. Many veterinarians are marking up compounded products and selling them for the same price as FDA-approved products. As the laws are currently written, this is not correct. Many products that are being used are not approved for such use.
Map-5 and Chondroprotec are two products currently used by some as generic Adequan. Map-5 has only been approved for use as a preservative for semen, and Chondroprotec is approved for use as a topical wound dressing. Using these products as injectable substitutes for Adequan is not correct.
The answers to this current compounding problem are as complex as the problem itself. Veterinarians have a real concern about the lack of drugs available for treatment.
"We as practicing veterinarians are going to have a dwindling source of legitimately produced drugs," Mitchell said. "The market is small and the cost of proving the efficacy and safety in medications is high, and I think the compounding situation is doing a great deal to threaten further research and development of products."
Mitchell hopes that changes are made in the FDA approval process. Clients are faced with a difficult choice when using expensive medications for their horses, and the chance to save money and still treat their animals is much of what currently fuels the pirated drug trade. If the approval process for FDA drugs were not as intense, then perhaps legal drugs would not be as costly and would make pirated drugs less attractive.
"There are a number of extremely useful equine drugs that would sell $1- to $5-million a year," said Gary White, D.V.M., from Sallisaw, Oklahoma, at the round-table discussion. "No one is going to invest the time and money to go through the current approval process for that amount of return."
Perhaps the FDA will re-evaluate its approval process to allow more equine drugs on the market at more reasonable prices. The issue is a double-edged sword, however, because clients are used to safe, effective products and no one wants to see this standard lowered.
Education required
Participants at the round-table discussion all agreed on the need for education among veterinarians about current rules.
"Many veterinarians are ignorant of the compounding laws, the difference between compounded and generic drugs, and FDA-approved medications," Mitchell said. "They see these [non-FDA-approved drugs] as a way to make a viable living and keep their clients happy."
Trainers and horse owners need to be educated as well. "If they don't know what they're doing is ineffective or wrong or improper, we [veterinarians] can't expect them to follow rules they don't know or understand," White said.
Horse owners should ask their veterinarians about some of these products if their tack trunks contain compounded or generic medications. They should become more knowledgeable about what may and may not be purchased and used, and they should encourage veterinarians to push for changes that could make more equine drugs available and keep the cost of those drugs reasonable.
Kenneth L. Marcella, D.V.M., is a practicing veterinarian in Canton, Georgia.
