Dr. Mark is a veterinarian. He has been working with dogs for more than 40 years.
What Is Trilostane?
Trilostane (sold under the brand name Vetoryl and also available in a liquid formula) is an FDA-approved medication that inhibits an enzyme (3beta-hydroxysteroid dehydrogenase) that is necessary to produce cortisol and other steroids. (1)
Cortisol is the hormone that pets (and humans!) produce when they are stressed. Trilostane is used to control the negative effects of too much cortisol and other steroids.
What Is Trilostane Used for in Dogs and Cats?
Trilostane has been prescribed for over 20 years to treat dogs with Cushing's disease (hyperadrenocorticism, or HAC)—both pituitary-dependent (PDH) and adrenal-dependent (ADH). About 75% of the dogs treated with this medication have fewer clinical signs, like excessive urination, muscle weakness, and excessive panting. Others cease showing clinical signs altogether. (2)
Many of the cats (about 60%) that are diagnosed with Cushing's also have diabetes, and normal therapies are not able to control that disease. Cats that are treated with trilostane are also able to regulate their diabetes. (3)
How Long Can Dogs and Cats Live on Trilostane?
A dog that is being treated with trilostane will live about 2 and a half years (900 days). Dogs that suffer from HAC and are not treated only live about a year and a half (292–564 days). (4) Cats also live about this long. (3)
Not only do dogs live longer when being treated with this medication, but they also have a better quality of life once the symptoms of the adrenal gland disease are treated. In cats, other diseases like diabetes can also be regulated after trilostane treatment.
Other Uses for Trilostane in Veterinary Medicine
Alopecia X is a condition seen in Pomeranians and some other breeds where the dog loses hair for an unknown reason. Some dogs respond to neutering and others to melatonin, but some only respond to trilostane. (5)
How Is Trilostane Given?
When it was first introduced, trilostane was only available in capsule form, and since few strengths were available, dogs were treated by weight class instead of getting an individual dose. Since that time, Dechra (the company that produces Vetoryl) has begun producing capsules in various sizes so that dogs can be given a lower and more accurate dose.
Some pharmacies also introduced a liquid suspension so that small dogs and cats could be treated more accurately and pets who would not take pills would be easier to treat. The liquid form is also available in several flavor options that dogs are more likely to accept (beef, chicken, bacon) and others for cats (tuna, salmon).
The liquid or capsules are given orally once or twice a day, usually with a meal. The medication should be given at the same time every day to prevent excessive changes in the amount of trilostane in the body.
There are advantages to both forms of medication—which is best for you may depend on your pet.
Pros and Cons of Trilostane Capsules
Recommended treatment method.
Difficult to dose small dogs and cats.
Clear amount of medication given per dose.
Pros and Cons of Liquid Trilostane
More accurate dosing for small dogs and cats.
Must be prepared by a compounding pharmacy.
Easy to use for pets that will not take pills.
Medication may not be spread evenly throughout the liquid, so doses may be harder to pinpoint.
Several flavors available (e.g., tuna or salmon).
Do You Need a Prescription for Trilostane?
Trilostane is only available with a prescription. The veterinarian will provide a prescription only when Cushing’s has been diagnosed by testing. Once you have a prescription, you can order trilostane online.
What to Do If Your Pet Misses a Dose
If you forget to give one dose, just skip it and give the next dose at the regular time. Do not give two doses, as you can overdose your dog. There are several apps available to remind you to give medication every twelve hours.
If you are going to be away and miss several doses, it is important that you find someone else to give the medication.
What Happens If I Stop Giving My Dog Trilostane?
Do not stop giving trilostane without consulting the veterinarian who has been treating your dog.
If you stop the medication, your dog will most likely return to the hyperadrenocorticoid state, and the negative effects of that problem can return. In some cases, the medication may be less effective when started up again. (This has only been documented in Alopecia X.)
If you are concerned that your dog is experiencing negative side effects because of the medication, call your veterinarian and discuss this with them before stopping trilostane. The veterinarian may recommend that you stop using the medication until your dog can be hospitalized for blood tests.
How Long Does It Take for Trilostane to Start Working?
Since cortisol and other hormones are produced throughout the day, the enzyme inhibitor in trilostane starts working as soon as it is absorbed by your dog. The highest levels of trilostane are from 1.7 to 3.8 hours after taking the pill. (6) It usually takes at least a day before any of the symptoms will go away.
The amount of time it takes to clear up all of the clinical signs of Cushing's will vary. Many dogs with this disease develop high blood pressure, which did not clear up even after a year of treatment. (7) The skin problems seen with Cushings in dogs also take several months to resolve. (8)
Trilostane stops working in less than 12 hours, though, which is why current recommendations are to give a lower dose twice daily. Clinical signs of Cushing’s disease do go away in dogs that are only treated once a day, but they go away faster in dogs treated twice daily.
Potential Side Effects
Does trilostane make dogs sick? Dogs with pituitary or adrenal tumors are already sick, and in most cases this medication will help them get healthier. There are potential side effects in some dogs, like vomiting, diarrhea, lethargy, and a lack of appetite. (1) Some dogs just need a reduced doseage, but others may need to stop taking the medication. Contact your regular veterinarian if you notice any side effects.
About 15% of dogs can develop hypoadrenocorticism (Addison’s disease) after 2 years of trilostane treatment. (9)
Most of these side effects go away after the drug is stopped, but in rare instances, dogs may experience permanent adrenal gland damage and die. If your dog develops diarrhea, vomiting, or collapses, a veterinarian should be contacted immediately.
Risk Factors and Special Precautions
It is important to recheck your dog's cortisol levels periodically since some dogs will develop low hormone levels as a result of long-term use of the medication. (10) There are no reports of allergies or hypersensitivities to the drug, but the pet needs to be watched after the dose is given. If there is swelling around the eyes, raspy breathing, hives, or red skin, it could be an allergic reaction and is an emergency.
Deaths that have been reported are not from allergies, however—they are after long-term use. Longevity studies also show that the benefits of treatment outweigh the risks, as there is a greater risk of death—and lower quality of life—if dogs are not treated.
Can Trilostane Cause Liver Damage?
Trilostane is relatively safe, but its use does need to be monitored more carefully in patients that already have liver or kidney disease. (1) It is metabolized in the liver and excreted in the urine, so both of those organs are important to remove it from your dog’s body. However, trilostane does not cause liver damage.
Known Drug Interactions
If your dog is diagnosed with Cushing’s and is being treated, it is vital that you tell your veterinarian about any other medications you give them, including supplements, herbal therapies, and Chinese traditional medicines.
Any medication that depresses steroid production, like ketoconazole, can cause your dog to become much worse. Some of the drugs known to interact with trilostane include:
- potassium supplements
- potassium-sparing diuretics
- ACE inhibitors
Trilostane Overdose in Dogs
There are several potential causes of death in dogs taking trilostane. If too much is given, or if it is given at a dose that is too much for them to handle because of pre-existing liver or kidney disease, they can overdose.
Unfortunately, dogs can have reactions even at a low dose. The best methods to prevent an overdose are to give the medication according to your veterinarian’s recommendation and by taking your dog in for frequent monitoring of cortisol levels. They can adjust the dose if the medication is too effective.
What Happens If You Touch Trilostane?
If you touch Trilostane when treating your dog, the first thing you should do is wash it off with plenty of running water and soap. (11) Some people can be sensitive to the medication and will develop a rash. If you notice any abnormalities, you should visit an emergency hospital. You can avoid skin contact by never breaking open the capsules, and if using the liquid formula, only using a dropper.
You should always wash your hands after giving your pet this medication just in case there is any contact that you are not aware of.
Because of the medication’s effect of blocking steroid production, pregnant and nursing women should avoid handling it.
This medication is expensive, like other alternative medical therapies for Cushing’s disease, but not nearly as expensive as surgical therapy or radiation. Even a small dog will need about $15 per week in Vetoryl capsules ($780 per year), and a medium-sized or large dog will need more. The liquid formula is also a little more expensive since it has to be compounded for each pet.
Besides the cost of the medication, there are going to be numerous veterinary visits for cortisol testing.
How to Store Trilostane
Vetoryl capsules should be kept in their original packaging so that they are not exposed to light. The package can be kept at room temperature.
Liquid trilostane should be kept at room temperature (about 25°C, or 68–77˚F), but be sure to read the label to check the manufacturer's instructions.
Both types of medication should be kept out of reach of children.
Although trilostane is considered the safest alternative available to treat a dog with hyperadrenocorticism, there are medical and surgical alternatives:
- Mitotane: Mitotane is a drug related to DDT and causes the destruction of the part of the adrenal gland that causes Cushing’s disease. In the past, this was the first treatment to help a suffering dog fight off the clinical signs, but it also led to more dogs developing Addison’s disease, which can be fatal. Dogs treated with mitotane usually live about as long as those treated with trilostane if their adrenal glands do not fail. (12)
- Ketoconazole: Ketoconazole, a medication usually used as an anti-fungal, is also an alternative for dogs that have problems with trilostane. Survival time is similar, and although fewer dogs are cleared of clinical signs, it does work well enough for some pets. (13) It is also much more affordable. The dosage necessary to control Cushing’s in cats is so high that it would cause liver failure.
- Adrenalectomy: Instead of just destroying part of the adrenal glands (mitotane) this is a surgical procedure to remove the entire adrenal gland. Dogs need to be supplemented with corticosteroids and mineralocorticoids for the rest of their life to avoid an Addison’s crisis.
- Hypophysectomy: This relatively expensive brain surgery requires that the tumor on the pituitary gland be removed. If the entire pituitary needs to be removed, the dog will need to be on several hormone supplements for the rest of their life.
- Radiation Therapy: This treatment is only available at some veterinary colleges or specialty practices that treat cancer. The results of one study revealed that dogs with radiation therapy for pituitary tumors only lived about 4 months, but one dog did live for 3 years. (14)
- Herbal Therapy (ginseng, melatonin, lignan): None of these alternatives address the root of the problem. They may help reduce cortisone, but no studies are available on whether they work or not.
- Lemetayer J, Blois S. Update on the use of trilostane in dogs. Can Vet J. 2018 Apr;59(4):397-407. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855282/
- Ruckstuhl NS, Nett CS, Reusch CE. Results of clinical examinations, laboratory tests, and ultrasonography in dogs with pituitary-dependent hyperadrenocorticism treated with trilostane. Am J Vet Res. 2002 Apr;63(4):506-12. https://pubmed.ncbi.nlm.nih.gov/11939311/
- Mellett Keith AM, Bruyette D, Stanley S. Trilostane therapy for treatment of spontaneous hyperadrenocorticism in cats: 15 cases (2004-2012). J Vet Intern Med 2013;27(6):1471-1477. https://pubmed.ncbi.nlm.nih.gov/24011349/
- Nagata N, Kojima K, Yuki M. Comparison of Survival Times for Dogs with Pituitary-Dependent Hyperadrenocorticism in a Primary-Care Hospital: Treated with Trilostane versus Untreated. J Vet Intern Med. 2017 Jan;31(1):22-28. https://pubmed.ncbi.nlm.nih.gov/27906457/
- Cerundolo R, Lloyd DH, Persechino A, Evans H, Cauvin A. Treatment of canine Alopecia X with trilostane. Vet Dermatol. 2004 Oct;15(5):285-93. https://pubmed.ncbi.nlm.nih.gov/15500480/
- Vetoryl (trilostane) 2015 drug insert, Dechra Veterinary Products, Pointe-Claire, Quebec.
- Smets PM, Lefebvre HP, Meij BP, Croubels S, Meyer E, Van de Maele I, Daminet S. Long-term follow-up of renal function in dogs after treatment for ACTH-dependent hyperadrenocorticism. J Vet Intern Med. 2012 May-Jun;26(3):565-74. https://pubmed.ncbi.nlm.nih.gov/22463105/
- Augusto M, Burden A, Neiger R, Ramsey I. A comparison of once and twice daily administration of trilostane to dogs with hyperadrenocorticism. Tierarztl Prax Ausg K Kleintiere Heimtiere. 2012;40(6):415-24. https://pubmed.ncbi.nlm.nih.gov/23242222/
- Braddock JA, Church DB, Robertson ID, Watson AD. Trilostane treatment in dogs with pituitary-dependent hyperadrenocorticism. Aust Vet J. 2003 Oct;81(10):600-7. https://pubmed.ncbi.nlm.nih.gov/15080470/
- King JB, Morton JM. Incidence and risk factors for hypoadrenocorticism in dogs treated with trilostane. Vet J. 2017 Dec;230:24-29. https://pubmed.ncbi.nlm.nih.gov/29208212/
- Safety Data Sheet for Vetoryl® (Capsules 5mg, 10mg, 30mg, 60mg and 120mg), Issue Date: 09/2017. https://www.dechra-us.com/Files/Files/ProductDownloads/us/Vetoryl-SDS-2017.pdf
- Barker EN, Campbell S, Tebb AJ, Neiger R, Herrtage ME, Reid SW, Ramsey IK. A comparison of the survival times of dogs treated with mitotane or trilostane for pituitary-dependent hyperadrenocorticism. J Vet Intern Med. 2005 Nov-Dec;19(6):810-5. https://pubmed.ncbi.nlm.nih.gov/16355673/
- Lien YH, Huang HP. Use of ketoconazole to treat dogs with pituitary-dependent hyperadrenocorticism: 48 cases (1994-2007). J Am Vet Med Assoc. 2008 Dec 15;233(12):1896-901. https://pubmed.ncbi.nlm.nih.gov/19072605/
- de Fornel P, Delisle F, Devauchelle P, Rosenberg D. Effects of radiotherapy on pituitary corticotroph macrotumors in dogs: a retrospective study of 12 cases. Can Vet J. 2007 May;48(5):481-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852601/
This article is not meant to substitute for diagnosis, prognosis, treatment, prescription, or formal and individualized advice from your veterinarian. Animals exhibiting signs and symptoms of distress should be seen by a veterinarian immediately.
© 2022 Mark dos Anjos DVM