The U.S. Food and Drug Administration reports the number of horses who died after receiving a compounded drug from Wickliffe Pharmacy in Lexington, Ky. has grown to four, and six others have become ill.
The FDA said initial testing on one lot of the pyrimethamine/toltrazuril compound indicates it contained higher levels of pyrimethamine than the labeling indicates. Adverse events associated with high doses of pyrimethamine include seizures, fever, and death.
Besides the tests that indicated elevated doses of pyrimethamine in at least one lot, the FDA noted that toltrazuril is not approved for use in horses.
Earlier this week Dr. Robert MacKay, veterinarian at the University of Florida's Large Animal Medicine, said two Thoroughbreds at a training stable in Ocala, Fla., had died and six others had neurological disturbances within 36 hours of administration of the compound.
The FDA said late May 15 it has received those eight reports as well as two reports from Kentucky of horses that had suffered adverse effects after receiving the compound. Four of those 10 horses have died.
The compounds were in two different lots: one a paste and one an oral suspension. The FDA reports all of the products in these lots are accounted for and are no longer in distribution.
The compounded drug is used to treat or prevent equine protozoal myeloencephalitis. MacKay said he was not sure if the treated horses had EPM or if the compound was being used as a preventative. On May 16, Wickliffe noted that the compound had been prescribed.
"The medication prepared by Wickliffe Veterinary Pharmacy was specifically made for and dispensed to the horses for which the medication was prescribed. No other animal patients received the prescribed medication in question," the company said in a statement. "The FDA has confirmed that all of the preparations are accounted for and secured. Accordingly, any risk of further adverse effects has been eliminated. There is no indication that any other products prepared by the pharmacy are unsafe in any way."
Earlier this week Wickliffe released a statement saying it had no indication that the preparation compounded at its pharmacy was unsafe in any way and that it had been prepared as prescribed. On May 16, the company said in a release it is working with federal officials on the investigation.
"(Wickliffe) is working cooperatively with federal health officials to learn more about the cause of the adverse events involving horses that received a compounded product from the pharmacy," the company said in a statement. "We wish to extend our deepest sympathies to the owners of, and equine professionals associated with, the horses that have died or been euthanized."
The FDA is working with the pharmacy and state regulators to investigate the adverse events.
"During the course of this on-going investigation into the adverse reactions, it has come to the attention of FDA that elevated doses of pyrimethamine may have been used by some practitioners with negative results," the FDA said in a release. "The usual dose of pyrimethamine in horses is 1 mg/kg, which has been shown to be safe for the treatment of EPM in an FDA-approved combination product containing pyrimethamine and sulfadiazine."
The FDA cautioned about using substances like toltrazuril that have not been approved for use in the horse.
"In general, FDA has serious concerns about unapproved animal drugs, including certain compounded animal drugs," the FDA said in its statement. "These drugs are not evaluated by FDA and may not meet FDA's strict standards for safety and effectiveness. Unapproved animal drugs also may not be labeled or advertised appropriately. Horse owners or caretakers should consult with their veterinarians about other therapies."
Drugs that have been evaluated and approved by FDA for the treatment of EPM include ponazuril, diclazuril, and a combination drug of pyrimethamine and sulfadiazine.
For more on compounding, read Frank Angst’s magazine feature from the Sept. 21, 2013, issue of The Blood-Horse.