In the wake of recent horse deaths following treatment with compounded drugs, the Animal Health Institute (AHI) is warning veterinarians to avoid these products and be cognizant of the risks and potential liability they present. In a news conference this week, AHI and others also called on the FDA to step up their enforcement of laws regulating manufacture of compounded drugs.
Presenters in the news conference included:
- Dr. Richard Carnevale: Vice President for Regulatory, Scientific and International Affairs, AHI.
- Peter Pitts: Former FDA Commissioner for External Relations, co-founder of the Center for Medicine in the Public Interest.
- Dr. Scott Stanley: Professor at UC Davis Veterinary School; involved in the toxicological testing of compounded products that are widely used in the horse racing industry.
Carnevale provided background, pointing out that FDA-approved trade-name drugs, and approved generic drugs, have undergone extensive and costly testing to verify safety and efficacy. Contents and concentrations are known and stated on the label, and label dosages are proven safe. Illegally compounded drugs manufactured by pharmacies from bulk ingredients carry no FDA approval, can vary widely in concentration of ingredients and often are unsafe.
Carnevale noted there are different types of compounding of veterinary drugs, with different legal status.
- In cases where approved treatments are unavailable or ineffective, custom manipulation of FDA-approved drugs, under the prescription of a veterinarian, to meet the need of a patient or group of patients in cases, is legal. This type of compounding typically involves customizing or re-formulating a drug that is approved for one species for use in another species of animal.
- Compounding drugs from bulk ingredients technically is illegal, but FDA allows this type of compounding in some situations, under prescription of a veterinarian with a valid veterinarian-client-patient relationship (VCPR), to address medical needs not met by existing approved products.
- Compounding drugs from bulk ingredients for general sale to veterinarians or consumers is illegal. In many cases, pharmacies compound large quantities of bulk materials to mimic FDA-approved products and sell the compounded drugs at steep discounts. These drugs have none of the safety and efficacy assurances that come with FDA-approved drugs.
Recently, 10 horses in Kentucky and Florida suffered adverse effects after being treated for equine protozoal myeloencephalitis (EPM) with a compounded drug containing pyrimethamine and toltrazuril. Testing has shown that at least one lot of the drug contained higher levels of pyrimethamine than the label indicated, resulting in seizures, fever and death. Four of the horses involved died or were euthanized while six are recovering.
In addition to the dangers presented by these unapproved drugs, Carnevale says their availability reduces the incentive for legitimate drug companies to invest in the research, development and testing required tointroduce new FDA-approved products.
Dr. Scott Stanley, from the UC-Davis Veterinary School, said his group has been analyzing and tracking illegal compounded drugs for 15 years. They have found that concentrations of active ingredients often are far below or far higher than those in the approved drugs they mimic. Veterinarians using these drugs have no way of knowing correct dosages or treatment intervals, resulting in problems ranging from poor efficacy to significant danger.
Peter Pitts added that while the FDA has stepped up their enforcement of laws regarding compounding in human medicine, enforcement in veterinary medicine has been lax, and some veterinary pharmacies openly manufacture and market illegally compounded drugs.
Stanley said most illegal compounding of veterinary drugs takes place in the equine and companion-animal sectors, rather than in food-animal medicine, and that food-animal veterinarians generally are very cautious with the types of products they use due to concerns over residues and food safety. Carnevale added though, that some compounded products such as knock-off antimicrobials or combination drugs for food animals have turned up, and he advises veterinarians to work with trusted suppliers and brands. Unusually low prices for a drug or drug combination should serve as a red flag suggesting the product could be illegally compounded.
The HealthyAnimals.org website includes additional information on drug compounding.