Unethical medication production and marketing continues to be a serious problem in the equine industry worldwide, said Joe Bertone, DVM, MS, Dipl. ACVIM, in his presentation “Drug Quality and Equine Veterinary Practice” at the 2002 American Horse Publications convention on June 21. “The equine industry is a huge target for snake-oil salesmen,” he stated. “There is more ‘stuff’--and that’s being nice--propagated in equine medicine than in any other field I’ve experienced.”
The problem is not with the major manufacturers. Rather, the problem is with unethical compounders (not to be confused with ethical ones) and manufacturers who skirt the regulatory system in order to sell cheaper, “knockoff” products to unsuspecting owners and veterinarians.
COURTESY MERIAL LIMITED
A study of 11 compounded ivermectin products found that only one contained approximately the labeled amount of ivermectin.
Why are these products bad? Because in many cases, the materials used to make these products are of lower quality than those used by reputable manufacturers, and might not even be the products they are claimed to be. This means that when you give your horse one of these medications, you might not only be giving him a lower or less pure dose, but the compound might not even be something his body can use. Having sub-optimal levels of active ingredients won’t necessarily hurt your horse, but what could hurt or even kill him is not getting the right type and dosage of a medication he needs.
Bertone explained that this problem is so widespread in the horse industry because:
- The horse industry is very competitive. We are very susceptible to something that claims it will make our horses run faster, jump higher, or otherwise perform better.
- The horse is a companion animal with livestock health needs. We are used to spending a significant amount of money on health care for these large animals, and love them enough to spend even more.
- The equine medication industry is one with very little regulation in a highly regulated society. We are accustomed to seeing human products that have exactly what the label says they do, so we assume that all products are correctly labeled; unfortunately this is not always the case with equine medications.
- The ignorance of owners and veterinarians alike allows this to continue. Most owners and veterinarians are simply in the dark about how widespread illegal compounding and labeling practices are in equine medications.
In the United States, there are three classifications of equine medications. These include:
- Food and Drug Administration (FDA)-approved pioneer drugs. These drugs are the original ones researched and developed by major manufacturers at a cost of $10-20 million per equine product. They set the standard for the imitators.
- FDA-approved generic drugs. After three to five years in which the pioneer products are protected from competition in order to allow them to recoup their development costs, generic drugs can come onto the market. These must have the same chemistry and manufacturing, but their manufacturers are not required to conduct safety/efficacy testing. The key word is that the generic must be “bioequivalent” to the competing pioneer drug, meaning it must have the same quality of ingredients.
- Compounded drugs. “Compounding has little enforced regulations in terms of quality,” commented Bertone. These drugs are manufactured by pharmacies or individuals, carry no FDA approval status, and are not required to adhere to Good Manufacturing Practices (GMPs). Sometimes they are safe and necessary (more on this in a moment), but this class of drugs is the one people need to be careful of. “Under no circumstances can a compounded drug give you the same quality as the pioneer drug,” Bertone emphasized.
The Animal Medicinal Drug Use Clarification Act of 1994 states that it is illegal to produce a compounded drug designed to treat a disease or condition when an FDA-approved drug for the disease or condition is available. As an exception to this rule, compounding a particular drug is legal when the approved drug is not available in the required dosage form or concentration.
“First of all, I’m a big supporter of this practice,” Bertone said. “I support people who do good work, and they support my views on this issue. This is an essential need in veterinary medicine because there aren’t enough FDA-approved drugs in useful formulations for horses. Many pharmacies do this right.” However, he added, compounded drugs are the ones most often made poorly.
One problem is the amount of active ingredient in the product. Compounded drugs have been found to have as little as 6% of the active ingredient claimed on the label, whereas FDA-approved products must have a minimum of 90% of their labeled values. For example, a study by Merial Limited in which researchers purchased and tested 11 compounded ivermectin products found unacceptably low levels of ivermectin in all but one (see chart above). “And that’s only for that sample!” Bertone exclaimed. “Who knows what you get with another batch!” Aside from ineffectiveness, this kind of dosing contributes to parasite resistance by delivering non-lethal amounts of the drug.
If a compounded drug varies from its labeled amount of active ingredient, it usually contains less of the ingredient because it’s cheaper to produce. However, a few instances of products with higher amounts than those labeled have been found; depending on the drug’s level of toxicity in the horse, this could be a worse problem than ineffectiveness.
Some inconsistency of product content with labels is because of the quality of materials some compounders use. Many U.S. sources of these materials are expensive because they are high-quality; however, many compounders get their materials more cheaply from other countries. The quality is often not as high, or it might not even be the material requested, explained Bertone. For example, clenbuterol (a bronchodilator) has been replaced with albuterol--which sounds the same, but is not used at all by the horse’s body when administered orally.
Active ingredients aren’t the only ones substituted. For example, omeprazole (the active ingredient in GastroGard ulcer medication) is mixed in an FDA-approved emulsified suspension that protects it from being broken down in the stomach before it can do its job. But if a compounding pharmacy uses a different formulation for the suspension, that breaches the patent for the suspension. This is significant because in water, 4% of the omeprazole will degrade to inactivity in eight days (according to a compounding textbook). In 18 days, 8% will have become inactive; such a product would be all but useless after spending time on the shelf.
Some veterinarians view compounded drugs as a profit source and sell them to clients at a price similar to that of the FDA-approved drugs. However, this practice is forbidden by federal regulations.
Why We Use This Compounded Stuff
“The typical comment is that compounded drugs are less expensive,” said Bertone. But he describes using compounded products that don’t need to be compounded (those that mimic products that are approved for use in horses in useful formulations) as “inappropriate, unscientific, and unethical.” He also notes that using these “knockoff” products rather than approved ones decreases the incentive for veterinary medication development.
Buying it because it is cheaper is sound logic only if the approved drug is a drug approved for use in people and expensive to the point that it inhibits therapy. One example is aldosterone administered topically in the eye, which is prohibitively expensive at around $400 per tube of Vasopressin (approved for human use). The compounded version for horses usually costs around $20 per tube, according to Bertone.
In order to treat the horse, the very least you should know is what you are putting into his body, said Bertone firmly. “The only way to know this is for sure is to use FDA-approved drugs. Why? Because the manufacturers of approved drugs have to use GMPs. These products deliver exactly what they say on the label.” Using products from reputable compounders (more on this in a moment) is usually fine, but sometimes they unknowingly get poor (or incorrect) materials from their sources, he said.
What about regulating compounded drugs? “The FDA is much more concerned with food animals,” Bertone explained. “There is very little compounding in that industry. But while horses mean a lot to us, they don’t mean much to the government. We need the public to be aware of this problem; that will stop more of this than the government can touch. It’s like police work on seat belts—you have to have public support or it won’t work.
“I give this talk to veterinarians all the time who don’t know it’s a problem," said Bertone. "We have to educate both clients and veterinarians on this issue.”
Spotting Snake Oil
The average horse owner or veterinarian can’t spot a poor product visually, but there are ways to avoid problems. Horse owners should check with their veterinarians on whether compounded products are being used, and if so, whether the veterinarian trusts this compounder to make quality medications.
“Call and ask if the company compounds Ivermectin (or any other product that’s approved for horses and doesn’t need to be compounded),” suggests Bertone. “If they do, don’t use them. If they’re trying to get by with that, what else might they be doing?”
Another thing to look for is an expiration date on a compounded product. “Regulations state that a medication must have an expiration date no later than three months after its manufacture,” he said. “I’ve seen them with expiration dates of years beyond the formulation date.”
A third tell-tale might be a label that states that the drug is sterile. “No compounded injectable drug can say that it’s a sterile solution, because that implies direct testing (the procedure for which can contaminate the sample),” Bertone explained. Any drug that is labeled as sterile will be unapproved and is obviously trying to be passed off as something it isn’t.
Use the pioneer drugs whenever possible. “Go for the stuff made by reputable manufacturers,” Bertone recommends. “Compounding is a cheap way to get a label, but this doesn’t necessarily get you the right product. Clearly a drug needs to be of excellent quality to perform optimally. Get the right drugs--you and your horses are worth it.”
About the Author
Christy West has a BS in Equine Science from the University of Kentucky, and an MS in Agricultural Journalism from the University of Wisconsin-Madison.