Toltrazuril for Goats
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-by Karen Kopf TOLTRAZURIL, OR “TOLT” — check any forum, and you’ll find recommendations for its use to combat coccidia in goats. It’s a hot topic among producers because it can’t be found in a feed store or prescribed by a veterinarian in the United States. Using, buying, or selling toltrazuril for goats is illegal here. Despite this, producers still suggest it as a treatment and even recommend illegal sources.
The Food and Drug Administration (FDA) regulates all drugs in the U.S., and medications must go through an approval process to be licensed for manufacture or use. Furthermore, federal law prohibits the use, importation, and sale of drugs that the FDA and EPA haven’t approved. The EPA? Yes. The Environmental Protection Agency.
What is toltrazuril for goats?
Toltrazuril and its metabolite, ponazuril (toltrazuril sulfone), are triazine-based antiprotozoal drugs. Only ponazuril has been approved for use in horses in the U.S., under the trade name “Marquis.” Toltrazuril is licensed and marketed under the trade name “Baycox” outside of the U.S. by Bayer of Germany and Elanco of Canada. Mexico also produces a licensed toltrazuril product labeled “Zuricox.” All require a veterinary prescription.
Of these, only Elanco shows goats on its Spanish-language label; in Canada, it’s only approved for use in cattle, sheep, and swine. It’s also used in birds, though not on this label.
According to FARAD (Food Animal Residue Avoidance Databank), there are currently only 26 drugs approved and labeled for goats in the U.S. As a result, many of the drugs frequently used for goats are “off-label” or “extra-label,” which is the administration of an approved drug, under the advice of a veterinarian, for a species or condition other than the drug’s original purpose.
Can I use toltrazuril for goats off label?
The extra-label use of Toltrazuril for goats must be fully documented in the veterinary record. Any use of drugs in designated food animals, such as goats, must have a scientifically established withdrawal period to ensure that no traces of the drug can enter the human food supply. The challenge in determining the extra-label use in other species is that not all animals metabolize at the same rate.
According to FARAD, “Estimation of a withdrawal interval of a drug across species should be approached with extreme caution.” Not only is the withdrawal time impacted by metabolism but so is the recommended dosage.
Toltrazuril is considered an unapproved bulk drug substance and must be compounded to form a finished drug. Compounding combines or alters ingredients to create a medication tailored to a specific individual.
Any use of drugs in designated food animals, such as goats, must have a scientifically established withdrawal period to ensure that no traces of the drug can enter the human food supply. The challenge in determining the extra-label use in other species is that not all animals metabolize at the same rate.
Compounding can be done by a licensed and inspected pharmaceutical company from an approved finished drug — such as when a patient is allergic to an inactive component of a finished drug, to offer an allergen-free version. Compounded medications themselves — even when approved finished drugs are used — aren’t approved by the FDA, as they aren’t tested or regulated for purity or potency.
When we will toltrazuril for goats be approved?
Toltrazuril for goats must go through the FDA nomination and evaluation process to gain approval as a finished drug. It was submitted June 27, 2022 by Wedgewood Pharmacy, Docket No. FDA2018-N-4626, listing the intended species as canine, feline, equine, other small mammals, reptiles, camelids, and assorted large and small exotic/zoo species (all nonfood animals).
The FDA classified the submission under 503A Category 3: Bulk Drug Substances Nominated Without Adequate Support, which prevented Wedgewood from entering the evaluation phase. It isn’t the first time toltrazuril has failed an approval process.
What about elsewhere in North America?
While marketed in Canada since October 21, 2010, it was initially offered through Canada’s Emergency Drug Release Program from 1992 to 1998. From 1998 to 2005, it was available to a few veterinarians under the Investigational New Drug Program for use in piglets.
After reviewing the data, Health Canada rescinded the submission and recalled all Baycox in 2005. They determined that “the risks outweighed the benefits.” Ponazuril (toltrazuril sulfone, produced in metabolizing toltrazuril) couldn’t be ruled out as a possible carcinogen.
What happened between 2005 and 2010? If toltrazuril has been approved in other countries that are more stringent in regulating their food supply than the United States, why hasn’t it been approved here? That’s a great question.
Possible environmental factors
While we don’t know why the U.S. hasn’t approved the drug, it’s interesting to read Elanco’s Summary of Product Characteristics, which states, “The metabolite of toltrazuril, toltrazuril sulfone (ponazuril) is a very persistent (half-life ca. 1 year) and mobile compound and has adverse effects on both the growth and emergence of plants.
While compounds may be labeled and approved in other countries, most toltrazuril found online is compounded by unknowns without oversight, many of which are untraceable.
Given the persistent properties of ponazuril, repeated spreading of manure from treated animals may lead to an accumulation in the soil and, consequently, a risk to plants. The accumulation of ponazuril in soil and its mobility also leads to a risk of leaching to groundwater.”
According to Elanco, Toltrazuril excretes from the body mainly in unchanged form (70%), but also as metabolites ponazuril (toltrazuril sulfone) in the feces and partially in the urine. This would undoubtedly interest the EPA in the U.S.
Getting toltrazuril for goats illegally could have serious ramifications.
For many producers, the illegal status and environmental impact don’t outweigh the perceived value of the drug. Toltrazuril interrupts the development of coccidia, unlike the coccidiostats currently approved. Coccidiostats don’t kill the organism; they disrupt the shedding of oocysts. In using toltrazuril, producers risk legal repercussions and potential herd health.
While some sources may have compounds labeled and approved for use in other animals in other countries, most toltrazuril found online is compounded by unknowns without oversight, many of which are untraceable.
One of the greatest dangers in using an illegal, unregulated, compounded substance, however, is that neither effectiveness nor safety is guaranteed. Many producers have lost animals as a result; some to underdosage, some to overdosage, with no recourse.
Fraud in pharmaceuticals is a real and present problem.
On June 12, 2020, the FDA issued a warning letter, MARCSCMS 595556, to Rapid Equine Solutions, LLC:
b. Potency Issues In addition, the toltrazuril/ pyrimethamine paste drug product that you compounded was adulterated under Section 501(c) of the FD&C Act, 21 USC § 351(c), in that its strength differed from, or its purity or quality fell below, that which it purported or was represented to possess. Our inspection revealed that on May 9, 2019, you compounded the toltrazuril/pyrimethamine paste drug product, Lot#20190509- 11, with a Beyond Use Date of November 5, 2019. (b)(4) of (b)(4) units were distributed.
The label for this product stated it contained 416 mg/ml of toltrazuril and 17 mg/ml of pyrimethamine. FDA collected samples of this product to conduct an analysis. FDA analytical results of one of the samples contained 13.5 mg/mL of toltrazuril, which is 3% of the declared concentration, and 361 mg/mL of pyrimethamine, which is 2122% of the declared concentration. Another sample contained 11.2 mg/ mL of toltrazuril, 3% of the declared concentration, and 307 mg/mL of pyrimethamine, 1808% of the declared concentration.
An example shows one drug is significantly under dosed — by 97%, and the second massively overdosed by 2022%. There is no safe way to administer this drug.
The FDA cautions: Animal drugs compounded from bulk drug substances are not FDA-approved and have not been reviewed by the FDA for evidence that they are safe, effective, properly manufactured, accurately labeled, and adequately packaged.
Further, when the compounded drug is administered to a food-producing animal, the FDA has not reviewed evidence supporting conditions of use to protect against harmful drug residues in edible tissues (meat, milk, eggs, etc.). Compounded animal drugs also lack post-market controls.
In this example, one drug is significantly under dosed — by 97%, and the second massively overdosed by 2022%. There wouldn’t be a safe way to administer this drug.
Even if the drug were properly labeled, there are other dangers to consider: Is the bulk drug properly mixed, stored, sterile, within the effective date when compounded, and is an effective date for the mixture known? Where was the bulk drug sourced? Is it free of contaminants? Is the potency known?
More cases of fraud.
In a separate case, Animal Health International was sentenced on a federal misbranding charge May 4, 2020. The United States Attorney Thomas T. Cullen and Special Agent in Charge Mark S. of the FDA’s Office of Criminal Investigation’s Metro Washington Field Office made this announcement:
“Manufacturers and distributors of veterinary prescription drugs must ensure that these medications are dispensed per their labels and federal law,” U.S. Attorney Cullen said. “Unauthorized distribution and off-label use of prescription medications endanger animals, livestock, and the general public. The Department of Justice will continue to work closely with the FDA to investigate and prosecute entities and individuals who engage in these types of unlawful business practices.”
Pursuant to the agreements by Animal Health International and Patterson, Animal Health International was ordered to pay a forfeiture money judgment of over $46 million, $1 million to the Virginia Department of Health Professionals, and a $5 million fine.
According to previously filed court documents, from 2012 through 2018, Animal Health International caused misbranded veterinary prescription drug shipments to be made throughout the U.S. by distributing veterinary drugs from its wholesale locations directly to end users, to unlicensed individuals, by distributing pursuant to prescriptions issued by a veterinarian who wasn’t licensed in the state to which drugs were shipped, and by distributing veterinary drugs pursuant to prescriptions issued by a veterinarian who didn’t have a valid veterinarian-patient relationship with the animals in question.
There are no guarantees and no legal means.
The reality is that almost anyone can illegally acquire toltrazuril powder. It’s then diluted to a suspension to a target potency, usually 2.5 or 5%, but it isn’t licensed, so there’s no guarantee of potency.
The suspension is available on eBay and through many revolving shadow storefronts that open and close on the internet to avoid detection or as a result of prosecution. Payment is in bitcoin or electronic transactions to names that don’t match the storefront or disclose the product being purchased.
There are no legal means of acquiring or administering toltrazuril to goats in the U.S. There’s no safeguard for the purchaser or the end user — the animals. While it may seem that the FDA imposes hurdles on the producer, they also offer protection. Consider carefully the use of pharmaceuticals in your herd.
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KAREN KOPF and her husband Dale own Kopf Canyon Ranch in Troy, Idaho. They enjoy “goating” together and helping others goat. You can learn more about them at Kopf Canyon Ranch on Facebook or kikogoats.org.
SOURCES:
- https://www.canada.ca/en/news/ archive/2005/07/statement-healthcanada-about-veterinary-drugbaycox.html
- https://www.vmd.defra.gov.uk/ productinformationdatabase/files/ SPC_Documents/SPC_1059684.PDF
- https://www.fda.gov/inspectionscompliance-enforcementand-criminal-investigations/ press-releases/animal-healthinternational-sentenced-federalmisbranding-charge
