Trilostane for Dogs: Side Effects, Dosage Chart and Rechecks

The most common side effects of trilostane (Vetoryl) in dogs, according to its FDA label, are a poor appetite, vomiting, diarrhea, tiredness and weakness. The label says to stop giving it and call your vet right away if you see any of them, because they can be the first signs of cortisol dropping too low. Collapse is an emergency.

Below you'll find what each side effect can mean, the dosage chart with a calculator, the recheck schedule your vet will follow, and how to give the capsules safely.

Trilostane treats Cushing's disease in dogs, a condition where the body makes too much cortisol. Vetoryl is the only drug the FDA has approved for both forms of the disease, the one driven by the pituitary gland and the one driven by an adrenal tumor (FDA). It works well for most dogs. It also asks a lot of owners: daily capsules with food, regular blood tests, and a sharp eye for the day something is off.

Trilostane Side Effects in Dogs

Think of trilostane as a dimmer switch on cortisol. The goal is to turn it down to normal. Most side effects happen when it turns cortisol down too far, which vets call over-suppression of the adrenal glands (the same picture as Addison's disease).

Common side effects

The Vetoryl label lists these as the most common:

• Poor or reduced appetite, including picky eating or eating slowly
• Vomiting
• Diarrhea or loose stools
• Lethargy or dullness
• Weakness

In the US field study of 107 dogs, diarrhea was seen in 31 dogs, lethargy in 30, vomiting in 28 and poor appetite in 27, so each of these showed up in roughly a quarter of the dogs. Other problems reported in that study included lameness or worse joint stiffness, urinary tract infections, shaking or shivering, ear infections, coughing, and skin or coat changes.

Don't wait these signs out. You can't tell at home whether vomiting is a passing upset or the start of an adrenal crisis. That takes a blood test, which is why the label tells owners to stop the medicine and call.

Serious side effects

Occasionally, the label warns, trilostane causes severe depression, bloody diarrhea, collapse, an Addisonian (hypoadrenocortical) crisis, or adrenal necrosis, where part of the adrenal gland dies and can rupture. These can be fatal. In the US field study, one dog died of adrenal necrosis about a week after starting treatment, and another had an adrenal rupture at about six weeks and recovered after the drug was stopped. Angell's internal medicine team calls adrenal necrosis an unpredictable reaction that is, fortunately, very rare (MSPCA-Angell).

Two lab-value changes are also common. Potassium often rises a little, which Angell says you should expect given how the drug works, and about 10% of dogs in the US study had a raised BUN (a kidney value) while looking clinically normal. Your vet tracks both at every recheck.

When to Call the Vet

• Go to your vet or an emergency clinic now: collapse or can't stand, severe weakness, trembling with vomiting, bloody diarrhea, not eating and not drinking, or your dog got into extra capsules.
• Stop and call your vet right away: vomiting, diarrhea, lethargy, a poor or picky appetite, weakness, or anything unusual. The label says to stop giving it and call your vet right away if you see any of these. It's the one time you stop the medicine before talking to your vet.
• Tell your vet at the recheck: how thirst, urination, appetite, panting and coat are changing. These tell your vet whether the dose is working.

For a possible overdose, call your vet or a pet poison line right away: ASPCA Animal Poison Control (888) 426-4435 or Pet Poison Helpline (855) 764-7661 (a consultation fee may apply). Take the labeled packaging with you. In the label's safety study, healthy dogs given three to five times the top starting dose, twice a day, developed an adrenal crisis and some died.

What Trilostane Does in a Dog's Body

Cortisol is the body's own steroid. A normal amount helps a dog cope with stress, fight infection and hold its body condition; too much weakens the immune system and wears the body down (FDA).

In Cushing's disease the adrenal glands, two small glands that sit on top of the kidneys, make too much cortisol. The FDA explains the two forms:

• Pituitary-dependent (about 80% to 85% of dogs): a tumor in the pituitary, a pea-sized gland at the base of the brain, sends out too much ACTH, the hormone that tells the adrenals to make cortisol.
• Adrenal-dependent (about 15% to 20%): a tumor in one or both adrenal glands makes the excess cortisol itself.

Trilostane works inside the adrenal cortex. It blocks an enzyme called 3-beta-hydroxysteroid dehydrogenase, an early step on the production line, so the gland makes less cortisol and, to a lesser extent, less aldosterone (the hormone that balances sodium and potassium) and fewer sex hormones (Vetoryl label). That aldosterone effect is why potassium tends to creep up and why some heart medicines need care alongside it.

It is a control, not a cure. The label's owner sheet says improvement shows in most dogs within a few weeks, but if the capsules are stopped or not given as directed, the excess cortisol and the signs come back. Trilostane also does nothing to an adrenal tumor itself.

What "working" looks like at home, per the label: your dog's drinking, urination and appetite drop back to normal, and panting and activity improve. A dramatic drop in appetite, or a dog that stops drinking, is the warning sign in the other direction.

Trilostane Dosage Chart for Dogs

Your vet picks the starting dose from your dog's weight and the capsule sizes, then changes it based on blood tests and how your dog is doing. Rows marked "FDA label" follow the current US Vetoryl label on DailyMed (package insert revised February 2024). The lower specialist start is clinical practice, not the label.

For information only. These are typical published dose ranges, not a prescription and not medically verified for your pet. Your veterinarian sets the dose after examining your pet. Never start, stop or change a medicine without their OK. (The one exception to 'never stop': the label's stop-and-call signs.)

Only give what your vet prescribed, at the dose they set.

How to read the chart:

• It is a starting range, not a target. The label says to begin at the lowest possible dose. After that, your vet adjusts from ACTH stimulation or cortisol tests, not from the calculator. The calculator covers the label starting range only.
• Your dog's dose may sit below the label range, and that is normal. Many specialists now start at about 1 to 2 mg/kg twice a day: AAHA reports that many authors of its endocrine guidelines start around 1 mg/kg twice daily (AAHA), and Angell's internists start at about 1 to 2 mg/kg twice daily, citing a 2011 study that found it as effective as higher once-daily dosing and safer (MSPCA-Angell). Follow your prescription.
• Why twice a day? Trilostane peaks in the blood about 1.5 hours after a dose and is back to baseline within about 12 hours, so in some dogs one daily dose doesn't cover the whole day (Vetoryl label).
• Capsules can't be split. Vetoryl comes in 5, 10, 20, 30, 60 and 120 mg capsules, and the label says not to open or divide them. Your vet combines sizes to reach a dose.
• Never adjust at home. The label notes an adrenal crisis can develop at any dose.

The Trilostane Recheck Schedule

Rechecks are how your vet keeps the dimmer in the right spot. The label lays out this rhythm:

1. Before starting: a full history, physical exam and baseline bloodwork. Liver and kidney disease need to be ruled out.
2. 10 to 14 days after starting: exam, an ACTH stimulation test taken 4 to 6 hours after the dose, and bloodwork with special attention to electrolytes (sodium and potassium), kidney and liver values.
3. 10 to 14 days after every dose change: the same checks again.
4. Once the right dose is found: rechecks at 30 days, at 90 days, and then every 3 months.

AAHA adds that the first recheck is mainly a safety check, so the dose may come down at that visit but should not go up (AAHA).

About the tests. The ACTH stimulation test measures cortisol before and after an injection of synthetic ACTH, which shows how much the adrenal glands can still respond. A very low result can show up before a dog looks sick, which is why it matters. Some vets instead use a single "pre-pill" cortisol sample taken before the morning dose, a cheaper option that matched owners' reports of control in one study (AAHA). Your vet will tell you whether to give the dose before the appointment and when to bring your dog in.

Your notes count. AAHA says your observations of thirst, urination, appetite and panting are the most important factor in deciding whether a dose goes up. A simple daily log of water bowl refills and accidents in the house helps. Urinary changes can have other causes too, such as urinary incontinence or an infection, so mention them.

How to Give Trilostane

• Always with food. Food improves absorption (Vetoryl label). VCA suggests giving once-daily doses in the morning (VCA), which also makes recheck timing easier.
• Give the capsule whole. Do not open it, empty it or split it.
• Wash your hands after handling the capsules.
• Pregnancy warning for people: do not handle the capsules if you are pregnant or trying to conceive. Trilostane caused birth defects and early pregnancy loss in lab animals. If a person swallows one, get medical advice and take the packaging.
• Missed dose: give it when you remember. If it's almost time for the next one, skip the missed dose and carry on as normal. Never give two doses at once (VCA).
• Don't stop on your own. The one exception is the label's stop-and-call signs above. Otherwise, stopping lets the cortisol and the signs of Cushing's return.
• Only for the dog it was prescribed for. Trilostane is a prescription drug in the US; never give a capsule to another dog.

Who Should Not Take Trilostane

The label says Vetoryl should not be used in dogs that:

• Are allergic (hypersensitive) to trilostane
• Have primary liver disease or kidney insufficiency
• Are pregnant (it caused birth defects and pregnancy loss in lab animals)

Its safe use has not been studied in nursing dogs or in males used for breeding. If your dog's bloodwork shows raised liver values, our guide to elevated liver enzymes in dogs explains what the numbers mean.

Drug interactions

Tell your vet about every medicine and supplement your dog takes. The ones that matter most:

• ACE inhibitors (such as benazepril or enalapril): use with caution. Both drugs lower aldosterone, which can upset electrolytes, blood volume and kidney blood flow.
• Spironolactone and other potassium-sparing diuretics: the label says they should not be used with trilostane, because both raise the risk of high potassium.
• Potassium supplements and ketoconazole: listed by VCA as needing caution.
• Mitotane: it also reduces adrenal function. The label says to wait at least a month after stopping mitotane, until the signs of Cushing's and a high ACTH test result return, before starting trilostane, and then to monitor closely.

Addisonian Crisis: The Risk to Know About

An Addisonian crisis (hypoadrenocortical crisis) happens when the adrenal glands make too little cortisol and aldosterone to handle stress. Sodium falls, potassium rises, and the dog can weaken and collapse. The label warns it can develop at any dose and at any point in treatment.

Signs to watch for, from the label and VCA:

• Lethargy, depression or a sudden drop in activity
• Not eating
• Vomiting or diarrhea
• Shaking or trembling
• Weakness and collapse

This needs a vet straight away. Treatment usually means hospital care with intravenous fluids and replacement steroid hormones (corticosteroids and mineralocorticoids). The label says the signs are usually reversible once trilostane is stopped, but not always. Adrenal function can take months to come back, and some dogs never regain it and need lifelong hormone treatment for Addison's disease.

Before there's any problem, ask your vet which clinic to go to after hours. If your vet gave you an emergency plan, follow it.

Other Treatment Options for Cushing's Disease

Most vets treat both forms of Cushing's with medication (FDA), but it isn't the only route:

• Adrenal surgery: the only way to cure Cushing's is to remove an adrenal tumor that hasn't spread. The surgery is complex and risky, so the label suggests considering it for dogs that are good surgical candidates.
• Pituitary surgery: being studied in dogs but not widely available.
• Anipryl (selegiline): the only other FDA-approved drug for Cushing's in dogs, and only for certain uncomplicated pituitary cases.
• Mitotane (Lysodren): a human chemotherapy drug used extra-label. It destroys the cortisol-making layers of the adrenal gland and needs close monitoring (FDA). Angell reports similar survival times with trilostane and mitotane.

Left untreated, Cushing's puts dogs at risk of blood clots, kidney damage, high blood pressure and diabetes (BluePearl). As the FDA's veterinarian puts it, treating Cushing's "is a balancing act", but dogs can live a good life with close monitoring.

How to Store Trilostane

Keep the capsules in their blister cards at controlled room temperature, 77 °F (25 °C); short spells between 59 °F and 86 °F (15 °C to 30 °C) are fine. Store them out of reach of children and pets (Vetoryl label).

Trilostane FAQ

What's the difference between hypo- and hyperadrenocorticism?

Hyperadrenocorticism is Cushing's disease: too much cortisol. Hypoadrenocorticism is Addison's disease: too little. Trilostane treats the first, and its main risk is tipping a dog into the second.

What causes Cushing's disease in dogs?

Most cases come from a tumor, usually a benign one in the pituitary gland, less often one in an adrenal gland. It mostly affects middle-aged and older dogs and develops slowly, so early signs are easy to miss (FDA). Signs include drinking and urinating more, a big appetite, panting, a pot belly, thin skin, hair loss or repeated skin infections, and muscle loss.

Does trilostane cure Cushing's?

No. It controls the signs for as long as it is given. Only removing an adrenal tumor that hasn't spread can cure the disease.

How long does trilostane take to work?

The label's owner sheet says most dogs improve within a few weeks. Response varies from dog to dog, and the first recheck at 10 to 14 days shows your vet how the adrenal glands are responding.

Can I buy trilostane online without a prescription?

No. In the US it is restricted to use by or on the order of a licensed veterinarian, and it is only safe with the rechecks described above.

Is trilostane used for alopecia X?

Sometimes. VCA lists alopecia X, a hair-loss condition in dogs, as an extra-label use. Your vet decides whether it fits your dog and at what dose. See our guide to alopecia in dogs for other causes of hair loss.

Can cats take trilostane?

Only extra-label, under a vet's care. VCA lists lethargy, a poor appetite and dullness as side effects in cats.

Questions to Ask Your Vet

• Is my dog's Cushing's pituitary-dependent or adrenal-dependent?
• What is my dog's exact dose, and is it once or twice a day?
• When is the first recheck, and should I give the dose before the appointment?
• Which signs should make me stop giving it and call you?
• What is our plan if my dog collapses after hours?
• Which of my dog's other medicines or supplements could interact?

Originally written by Dr. Catharina Hjorth. Updated by the I Love Veterinary editorial team.

Sources

• FDA label (DailyMed): Vetoryl Capsules (trilostane), Dechra Veterinary Products, NADA 141-291
• FDA: Treating Cushing's Disease in Dogs
• AAHA NEWStat: Monitoring strategies for trilostane therapy in dogs with Cushing's syndrome
• MSPCA-Angell: Trilostane for the Treatment of Hyperadrenocorticism, Things Learned Over the Past 10 Years
• BluePearl Pet Hospital: Cushing's Disease in Dogs
• VCA Animal Hospitals: Trilostane
• ASPCA Animal Poison Control Center
• Pet Poison Helpline

This article is for general information and is not a substitute for advice from your veterinarian.