FDA approves Vetoryl Capsules for Cushing's disease

New molecular entity treats pituitary- and adrenal-dependent hyperadrenocorticism

May 15, 2009 (published)
By Jennifer Fiala

The U.S. Food and Drug Administration (FDA) OK'd a new drug to treat Cushing's disease, and while one veterinary endocrinologist applauds the development, Vetoryl (trilostane), like other drugs, needs to be treated with "a healthy respect," she says.

That comes from Ellen Behrend, VMD, PhD, Dipl. ACVIM. The professor at Auburn University's Department of Clinical Sciences within the veterinary college says there are "still a lot of unanswered questions" about trilostane, including whether or not it's safer than mitotane, a traditional treatment for hyperadrenocorticism in dogs. 

Mitotane is a human medication that's used off-label in veterinary medicine for the controlled destruction of adrenal tissue, leading to a decrease in cortisol production. 

Vetoryl, manufactured Penn Pharmaceuticals in Wales, is the first drug approved to treat pituitary- and adrenal-dependent canine Cushing’s disease, a condition that results when the body produces too much cortisol. According to distributor Dechra Veterinary Products, Vetoryl Capsules release the active ingredient trilostane to block the excessive production of cortisol by reversibly inhibiting the action of the enzyme 3-ß hydroxysteroid dehydrogenase. While treatment with trilostane significantly reduces serum cortisol concentrations, it has not been found to reduce aldosterone significantly, the company says

The safety and effectiveness of Vetoryl were supported by two field studies in the United Kingdom and one multi-center field study in the United States, an FDA Center for Veterinary Medicine news release says. Success was measured by improvements in ACTH stimulation test results and clinical signs (appetite, activity, panting, thirst and urination). 

Unlike mitotane, trilostane does nothing to effectively destroy adrenal cells, which might make it more appealing to general practitioners, says Dr. Mark Peterson, head of endocrinology at The Animal Medical Center in Manhattan. 

"I've been using it for two or three years, and I don't necessarily think one's better than the other," he says, explaining that most veterinarians find trilostane an attractive option because it does not permanently alter adrenal function. 

While trilostane is not considered to be cytotoxic, some patients have experienced long-term alteration of adrenal function, although the cause of this is unknown. Dr. Carlos Melian, an endocrinologist in Spain who has been using trilostane since 2001, says he treats most of his canine Cushing's patients with it. 

"In some dogs, there is adrenal necrosis," he says. "It's not common, but we know that it happens. We don't know why. We know side effects can happen, so we monitor (our patients) closely."

Mitotane, on the other hand, is derived from the insecticide DDT and is not tolerated well by some patients, experts say. 
"Many veterinarians are afraid of mitotane because dogs can get really sick if they don't have much experience using it," Peterson says. "You can get real bad side effects from mitotane, and it's harder to do that with Vetoryl."

FDA notes that the most common adverse reactions to Vetoryl are vomiting, lethargy, diarrhea, and anorexia.

Cushing's disease is known to be complicated and slow to develop; the early signs are not always noticed. Symptoms include increased drinking, increased urination, increased appetite, reduced activity, excessive panting, thin or fragile skin, hair loss, recurrent skin infections and enlargement of the abdomen. 

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