A Look Inside Your Horse's Compounded Medications
If your veterinarian deems a compounded medication a necessity, work with him or her to ensure your horse receives a high-quality, legally compounded product.
Photo: The Horse Staff
A trip to the veterinary clinic can be costly, and it's reasonable to expect that many horse owners will try to save a few dollars whenever possible. However, would they be willing to save money if they knew it was at the expense of their horse's safety and/or the efficacy of the treatment that is being administered? While often less expensive than their legally compounded counterparts, illegally compounded products should not be used to reduce treatment costs, and in most cases little is known about their safety, efficacy, and stability. Why? Because they have not been proven safe or effective by the Food and Drug Administration (FDA).
By definition, a compounded product is any drug that has been manipulated outside of its original, approved form as described on its approved label; this includes any manipulation, from adding flavor to increase palatability to completely replicating a chemical. Illegally compounded products are not subjected to the same rigorous safety and efficacy standards as name-brand and generic equivalent FDA-approved products. The FDA has made it clear that the compounding of a new animal drug from any unapproved drug or bulk active ingredient(s) is illegal. The compounding of new animal drugs from an approved human or animal drug also is illegal unless it fits within specific FDA guidelines.
Value of FDA Approval
Gaining FDA approval is a coveted event. To receive FDA approval, a company must prove the following:
- The drug is safe and effective in the specific specie(s) it will be used for;
- The manufacturing process will produce a consistent quality product from batch to batch; and
- The labeling is accurate and truthful and contains all necessary information to ensure the drug is able to be used safely and effectively; the label also must include the potential adverse effects of the product.
Joe Manning, DVM, MBA, a Merck Animal Health equine technical services veterinarian and former performance horse and equine reproduction practitioner, says it can take years for a product to gain FDA approval and become available to veterinarians and horse owners.
"Gaining FDA approval is not just a technicality in the process of launching a new product," Manning said. "It is the ultimate test for product safety and efficacy and ensures the product is going to help better the health and welfare of the horse."
The FDA continues to monitor the product even after the drug is approved. The manufacturer must continue to demonstrate that the product is safe, effective, produced consistently, and that all advertisements for the product are accurate and truthful.
"There is a peace of mind that comes with FDA approval for veterinarians," Manning explained. "Horse owners deserve this same peace of mind and should make sure their horses are only receiving FDA-approved products when available."
When Compounding Goes Wrong
The death of 21 polo ponies in 2009 brought the dangers of procuring and using incorrectly compounded products into the forefront of horse owners' minds. For the horse's sake, it is important this lesson is not forgotten. Because there is no FDA approval for compounded medications, it is up to the veterinarian to ensure the final compounded product contains the correct active ingredients and/or concentration of those ingredients. As a result, the veterinarian is at a greater risk for being found liable for adverse events and/or lack of efficacy.
"Horse owners need to have a conversation with their veterinarian about illegally compounded products," Manning says. "The American Association of Equine Practitioners recognizes that while the use of legally compounded products may fill a therapeutic void, it does not support the use of products that are not legally compounded, and neither do most veterinarians, but ultimately it is the responsibility of the horse owner to know what products their horse is being treated with and make sure they are receiving safe, effective treatments."
The Federal Food, Drug, and Cosmetic Act does not distinguish compounding from manufacturing or other processing of drugs for use in animals, and neither veterinarians nor pharmacists are exempt from the law's approval requirements for animal drugs. In certain limited situations, FDA regulations specifically permit the compounding of products. The FDA considers a variety of issues in determining whether to pursue enforcement action against compounded products, including the following:
- The existence or lack of a valid veterinary-client-patient-relationship;
- Whether there is an FDA-approved product that will effectively treat the horse;
- If the compounded product is prescribed by a licensed veterinarian and prepared by a licensed pharmacist under direction from the veterinarian;
- Whether veterinarians prescribing the compounded product comply with all aspects of federal extra-label drug use regulations;
- Whether the compounded product is made from an FDA-approved commercially available animal or human drug, not from bulk substance; the FDA has clearly stated that the compounding of an animal drug from unapproved drugs or bulk active ingredient(s) is in violation of the Federal Food, Drug, and Cosmetic Act; and
- The extent to which the use of compounded products is for use in situations where the health of the animal is threatened or suffering, or death may result from failure to treat.
However, veterinarians must consider the fact that in both cases-legally compounded products and potentially illegally compounded products where the FDA has used their "enforcement discretion" not to act-the products may not be manufactured on a consistent basis because they are produced by individual pharmacists and technicians, rather than inspected and approved facilities. Due to lack of regulatory oversight in manufacturing some compounded drugs might:
- Contain unsanitary components;
- Differ in strength; or
- Be mixed with other substances that could potentially reduce their quality and/or strength.
Less Than You Bargained For
There have been several studies that have proven illegally compounded products are not as effective as FDA-approved products.
The University of California, Davis, evaluated the effectiveness of illegally compounded omeprazole to GastroGard, an FDA-approved product used to treat equine gastric ulcer syndrome. The manufacturer of the illegally compounded omeprazole claimed their product does the same.
In the study 32 horses that were identified as having significant gastric ulceration were treated with either the illegally compounded omeprazole or GastroGard for 60 days. Of the 16 horses treated with GastroGard for the first 30 days, all had drastically reduced ulcer severity scores. The 16 horses treated with the illegally compounded omeprazole for the first 30 days, however, did not significantly improve.
Additionally, when the horses treated with GastroGard were switched to being treated with the illegally compounded drug for the following 30 days, their ulcers returned. The horses originally treated with the compounded formulation experienced significantly reduced ulcer scores after being treated with GastroGard for the remaining 30 days of the trial.
Another example study comparing the effectiveness of an illegally compounded drug to an FDA-approved product was performed by Gary White, DVM, and Arkansas Tech University. In this study researchers injected 30 horses with Complete Freund's Adjuvant, a model used to induce lameness in equine research, and then treated five days later with either Adequan i.m., an FDA-approved product used for treating joint deterioration in horses, a compounded solution of acetyl-d-glucosamine, or a compounded solution of chondroitin monosulfate. The producers of both illegally compounded formulations claimed their products treat joint deterioration. All horses received the intramuscular treatments every four days for four weeks at equal doses.
Evaluations of the horses revealed that horses treated with Adequan i.m. had significantly improved lameness scores, flexion, and stride length. Horses treated with either of the two illegally compounded products experienced significantly less improvement than those treated with Adequan i.m.
Another problem commonly seen in illegally compounded products is variation from what the product label says to what the product actually contains. Merck Animal Health conducted a study evaluating the potency of an illegally compounded formulation of altrenogest (a hormone therapy product used to suppress estrus in breeding and/or performance mares). The study revealed that the illegally compounded product actually contained a lower percentage of altrenogest than the label claimed and the potency, or strength, of the altrenogest was significantly less than the label claim even before the expiration date. In comparison, Regu-Mate, the only FDA-approved altrenogest, is closely monitored by the FDA to ensure that the product's potency is consistent with the label claim and that when properly handled and stored it remains it effective until the expiration date.
Compounded Products Are Not Generic Equivalents
It is important for horse owners to understand compounded products--whether legal or illegal--are not the same as a generic equivalent. Generic equivalent products are FDA-approved and have proven to have the same chemical makeup and purity as the pioneer (brand-name) product. Generic equivalents also have the same dosage form, strength, route of administration, quality, and intended use as the brand-name product. As is the case with all FDA-approved products, generic drugs must be manufactured according to the FDA's strict guidelines in federally inspected facilities. This is not true for compounded products.
A Time and a Place
It is also important that horse owners discuss the pros and cons of using compounded products with their veterinarian before treatments are administered. Compounded medications should be secured from a pharmacy whose products are screened routinely for purity and potency. Compounding should be considered only when the horse is suffering or could die if they are not treated and there is no FDA-approved treatment option that can be administered to that particular horse.
For example, pergolide is a human drug that is compounded at different dosages for use in horses with Cushing's disease. This is a legally compounded product because there is currently no FDA-approved treatment option and the FDA deemed that without treatment affected horses will suffer and eventually die from the disease.
Compounding: More Common than You Think
While there is a possibility for any equine health product to be compounded, here is a list of a few FDA-approved products that are often illegally compounded:
- Regu-Mate (produced by Merck Animal Health): An altrenogest product used to suppress estrus in breeding and/or performance mares. Regu-Mate is the only FDA-approved altrenogest. All others are illegally compounded;
- GastroGard and UlcerGard (produced by Merial): Products used to treat and prevent equine gastric ulcers. GastroGard and UlcerGard are the only FDA-approved products for equine gastric ulcer syndrome. All others are illegally compounded;
- Flunixin (Banamine, produced by Merck Animal Health) and its Generic: A non-steroidal anti-inflammatory used to relieve pain associated with musculoskeletal disorders and colic;
- Phenylbutazone (Bute) and its Generic: A non-steroidal anti-inflammatory used to relieve pain associated with musculoskeletal disorders;
- Adequan (produced by Luitpold Animal Health) and Legend (produced by Bayer Animal Health): Used to treat and prevent equine degenerative joint disease. Adequan and Legend are the only FDA-approved injectable joint products.
- Protazil (produced by Merck Animal Health) and Marquis (produced by Bayer Animal Health): Anticoccidial products used to treat equine protozoal myeloencephalitis (EPM) in horses. Protazil and Marquis are the only two FDA-approved EPM treatment options.
- Ventipulmin (Clenbuterol) produced by Boehringer Ingelheim: Bronchodilator product used for the management of airway upper disease, such as chronic obstructive pulmonary disease (COPD).
Horse owners need to communicate with their veterinarian about all of their horse health concerns, including the use of medications. An equine veterinarian should always be involved in the treatment decision-making process.
"Horse owners need to communicate with their veterinarian about all of their horse health concerns," Manning concluded. "This communication is key to ensuring horses are only receiving FDA-approved products and not being put at risk for unsafe or ineffective treatment."
Horse owners should consider this decision-making process:
- Request an FDA-approved drug or a generic equivalent when available for the treatment of their horse's condition; and
- When no FDA-approved pioneer or generic drug exists, work with your veterinarian closely as you consider the risks associated with compounded medications. If your veterinarian deems a compounded medication a necessity, work with him or her to ensure your horse receives a high-quality, legally compounded product.
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