Selenium and compounded drugs in horses

July 17, 2009

View of a heart muscle from a horse that died due to severe selenium deficiency. The lighter colored tissues are heart muscle cells that died prematurely.

In April, the equine world was shocked when 21 elite polo ponies at a Florida championship polo match died within minutes of each other.

The Florida pharmacy which mixed a preparation for the Lechuza Caracas polo ponies disclosed that selenium was the ingredient at the wrong strength. The concentrations were found to be 10 to 15 times higher than normal in the blood and 15 to 20 times higher than normal in the liver.

Due to the widespread coverage of the tragedy, horse owners may wonder about the role of selenium in horses and the safety of compounded drugs.

Selenium is a mineral found in soil that horses utilize as a component of an enzyme that helps protect cell membranes from the damage caused by normal cell metabolism. It also works in conjunction with vitamin E. In general, horses require about 1-3 mg of selenium each day.

Horses usually get the selenium they need while foraging. However, plants grown in selenium-deficient soils can be low in this mineral and, in turn, horses can develop a deficiency.

This can cause their muscles to break down, a condition called nutritional muscular dystrophy, white muscle disease, or muscular dystrophy.

Both foals and adult horses can become selenium deficient, and the clinical signs and severity of disease depend on the muscles affected. Many horses have mild or sub-clinical cases of selenium deficiency, with signs such as decreased immune function or impaired reproductive efficiency. Horses with acute cases, however, experience severe muscle abnormalities, and the prognosis for survival is often poor, especially if the heart muscle is affected, or for foals that are unable to stand or nurse.

On the flip side, too much selenium is toxic. This usually causes hoof problems, lameness, and hair loss from the mane and tail. This can happen when horses eat forage over a period of time that was raised in areas with high selenium levels in the soil, or were supplemented with too much selenium through products that contain the mineral. Acute toxicity occurs when horses receive a large dose in a short period of time, often resulting in death from multi-system failure.

As there are many products available to supplement horses that don't get enough, it is possible to give a horse too much of this essential nutrient if care is not taken. It is best to consult a veterinarian about the most appropriate selenium supplementation program for individual horses in a given area, and owners should be careful to administer the proper amounts.

Compounded drugs necessary under limited circumstances

The injection under scrutiny in the polo horse incident was what is known as a compounded drug, meaning it was formulated or modified by a pharmacy at the request of a veterinarian to meet specific needs.

At times, this is needed to best treat a patient, but because compounded drugs don't have the same rigorous evaluation and monitoring as manufactured drugs, they should be prescribed only when necessary. Compounding is regulated by the Federal Drug Administration (FDA) and individual state boards of pharmacy, both of which regulate drug use in veterinary medicine.

For drug compounding to be legal, several FDA requirements must be met. Only licensed veterinarians can prescribe compounded drugs, and they can write such a prescription only after they have examined the patient. Only veterinarians or pharmacists may prepare them, and pharmacists may do so only after receiving a valid prescription. In addition, compounding can only be done if an FDA-approved veterinary or human drug is not available for efficaciously treating the condition in the patient. Another requirement is that the health of the animal is threatened and suffering or death would result from failure to treat the patient.

For a drug to become FDA approved for use in animals, a sponsoring pharmaceutical company must provide convincing evidence that the new drug is safe and effective for treating the intended disease process.

"The FDA defines compounding as any manipulation of a drug that results in a new drug product," said Dr. Katrina Mealey, a Washington State University associate professor and board-certified pharmacist, as well as a board-certified small animal internist and clinical pharmacologist.

"This can include something as simple as mixing two drugs in a single syringe prior to injecting them. It includes grinding up tablets and mixing them with molasses in order to administer them to a horse orally. Compounding also includes fairly complex manipulation of drug and chemical products into capsules, pastes, or injectable drug formulations.

"This is allowed because the FDA recognizes that an approved drug may not be available to treat every disease in every patient," she said. "Thus, the FDA allows veterinarians to prescribe compounded drugs under limited situations. There are, however, profound disadvantages to using compounded drugs versus FDA-approved drugs in that are that there are no safety studies, efficacy studies, information about the stability of the product, or on the purity or potency of the final product. If an FDA drug is available, that is the safest one to use. Owners should talk with their veterinarian if they have questions about what is being prescribed."

Owners should also consider using a pharmacy accredited by the Pharmacy Compounding Accreditation Board (PCAB). Although unaccredited reputable compounding pharmacies exist, an owner can feel assured that a PCAB accredited pharmacy is reputable and meets official standards.

Jim Meyer, head of WSU's pharmacy located in the Veterinary Teaching Hospital.
"There are few PCAB accredited pharmacies in Washington, but in the absence of in-depth knowledge of an unaccredited compounding pharmacy's personnel, quality control, and equipment, I would rather deal with a PCAB accredited pharmacy by mail than count on chance," said Jim Meyer, head pharmacist at WSU's pharmacy, located in the veterinary teaching hospital in Pullman.

"Furthermore, by using a PCAB accredited pharmacy, clients are making a statement that they understand the need for and support quality compounding.

"As a pharmacist, I have been acutely aware of problems with compounded products and many compounding pharmacies, even before the polo pony incident," Meyer said. "I know of treatment failures, other deaths, contamination, inappropriate concentration of drug in the final product, and correct drug concentration but no bioavailability to the patient.

"Without this information, owners might not recognize the increased level of risk they accept when they choose a compounded product."

Another dilemma involving compounded drugs is that they may hamper the production of new FDA-approved drugs. "In my opinion, compounded drugs are a big problem for the equine industry - particularly the mimics, or compounded copies of FDA-approved drugs, made from "bulk drugs" - that are done because of price differentials," said Dr John Gay, a WSU associate professor and board certified specialist in veterinary preventative medicine and epidemiology who is a part of the Field Disease Investigative Unit.

"These drugs can be really risky because the imported 'bulk drugs' they are compounded from may be counterfeit, which may account for their low price in the first place. Horse owners need to realize is that if legitimate manufacturers begin to see that they cannot recover their research, development, and licensing costs, they will not develop new products and are likely to eventually leave the horse market entirely. To have these ethical drugs replaced by compounded drugs is bad, because it is the research done by those companies that determines efficacy of the drug and licensing that ensures it.

"Another problem is that at least some of the larger compounding pharmacies are really manufacturing drugs, but using the compounding umbrella to avoid the expense of having to obtain an FDA license to become a legitimate drug manufacturer," he said.

"Legitimate compounding pharmacies make compounded drugs on the basis of an initiating prescription and do not stock them in advance - that is manufacturing. The PCAB is developing a certification system for legitimate compounding pharmacies to help screen out these masquerading manufacturers from the legitimate compounders. Again, this type of compounding is a problem because it reduces the incentives for the legitimate manufacturers to remain active in the equine market."


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