Mitotane in Dogs

Mitotane is an oral prescription medication used in dogs to manage hyperadrenocorticism, also called Cushing’s disease. It is most often used when a dog has pituitary-dependent Cushing’s disease, though some dogs with adrenal tumors may also receive it when surgery is not the chosen path. The drug does not remove the underlying pituitary tumor, but it can reduce the body’s cortisol production and improve day-to-day signs such as increased thirst, increased urination, increased appetite, panting, skin changes, and a pot-bellied appearance.

This medication requires close follow-up with your vet because the line between effective control and too much adrenal suppression can be narrow. Dogs on mitotane usually need repeat exams, blood work, and ACTH stimulation testing to help guide dose changes. Many dogs do well for years with careful monitoring, but treatment is lifelong in most medically managed cases.

Mitotane is not the only option for canine Cushing’s disease. Standard medical management often uses trilostane instead, while some dogs with adrenal tumors may be candidates for surgery, and a smaller number may be referred for advanced imaging, radiation, or specialty endocrine care. The right plan depends on the type of Cushing’s disease, your dog’s overall health, your goals, and your household budget.

See your vet immediately if your dog on mitotane develops vomiting, diarrhea, weakness, collapse, severe lethargy, stumbling, or suddenly stops eating. Those signs can mean the medication is suppressing the adrenal glands too much and may signal an Addisonian crisis or another urgent problem.

Mitotane works by selectively damaging parts of the adrenal cortex, especially the zones that produce cortisol. In practical terms, that means it lowers the adrenal glands’ ability to make excess cortisol. This is why it can help dogs with Cushing’s disease, where chronic overproduction of cortisol drives many of the classic signs pet parents notice at home.

Treatment usually has two phases. First comes an induction or loading phase, when the medication is given more frequently to bring cortisol production down to a safer range. After that, dogs move to a maintenance phase with less frequent dosing, often weekly or divided across the week, based on your vet’s protocol and follow-up test results. Clinical improvement in thirst, urination, and appetite may happen within the first one to three weeks, while skin and body-shape changes often take longer.

Because mitotane actually destroys adrenal tissue rather than temporarily blocking hormone production, its effects can be more durable than some other medications. That also explains why monitoring matters so much. If too much adrenal tissue is affected, a dog can become under-suppressed and develop low cortisol levels, which can be dangerous.

Your vet will usually pair home observations with ACTH stimulation testing to decide when to stop induction and how to adjust maintenance dosing. Tracking water intake, appetite, energy, and stool quality at home is a meaningful part of treatment, not an extra detail.

The most important side effect of mitotane is excessive adrenal suppression, which can lead to iatrogenic hypoadrenocorticism. In plain language, the medication can push cortisol levels too low. Early warning signs often include reduced appetite, vomiting, diarrhea, weakness, lethargy, wobbliness, or a noticeable drop in normal water intake. Some dogs also seem depressed or less interested in food before more serious signs appear.

More severe reactions can include collapse, dehydration, electrolyte problems, and an Addisonian crisis. Rare neurologic effects such as ataxia, circling, apparent blindness, or head pressing have also been reported. Long-term therapy may contribute to liver changes in some dogs, especially if liver disease is already present, so your vet may recommend periodic chemistry panels in addition to endocrine testing.

Pet parents should not wait to see if these signs pass on their own. If your dog on mitotane vomits, has diarrhea, becomes unusually listless, stumbles, or skips meals, contact your vet right away. Many treatment plans include an emergency steroid such as prednisone for use exactly as directed if concerning signs develop, but the timing and dose should come from your vet.

Mitotane is also considered a hazardous drug. It should be handled carefully, ideally with gloves, and pregnant people should avoid handling it. Gloves are also recommended when cleaning urine, stool, or vomit after dosing because drug residue may be present.

Mitotane dosing is individualized, so this article should not replace your vet’s instructions. In general, dogs start with an induction phase, and a commonly referenced protocol is 25 mg/kg by mouth every 12 hours for about 5 days or until appetite and water intake begin to normalize or mild gastrointestinal signs appear. After that, your vet confirms response with an ACTH stimulation test and transitions to a maintenance plan.

Maintenance dosing is commonly based on weekly totals divided into two or three doses, but schedules vary. Some dogs receive medication about once weekly, while others need a split-week schedule. Dogs with adrenal-dependent disease may need higher doses than dogs with pituitary-dependent disease, and they may not respond as predictably. Because of that, dose changes should always be based on your vet’s exam findings, your home observations, and follow-up testing.

Mitotane is given by mouth and is absorbed best with food, especially a meal containing some fat. Pet parents should give it exactly as prescribed and should not double up after a missed dose unless your vet specifically says to do so. Since the dosing plan can be complex, the safest step after a missed dose is usually to call your vet for instructions.

Monitoring is a major part of administration. Your vet may ask you to measure daily water intake, appetite, and energy during induction. ACTH stimulation testing is commonly repeated after induction, again about a month into maintenance, and then every three to four months, though schedules can vary by case.

Mitotane can interact with other medications or make interpretation of follow-up testing more complicated, so your vet needs a full medication list before treatment starts. That includes prescription drugs, supplements, topical products, and any steroid-containing ear or skin medications. Corticosteroids are especially important to discuss because they affect adrenal function and may also be used intentionally as rescue medication if mitotane suppresses the adrenal glands too much.

Dogs being monitored for Cushing’s disease often need ACTH stimulation testing, and some medications can interfere with endocrine test interpretation. Your vet may adjust timing around testing or ask you to pause certain drugs before a scheduled recheck. If your dog has diabetes, liver disease, kidney disease, or another endocrine disorder, treatment may also need closer follow-up because changes in cortisol control can affect the rest of the body.

Mitotane should be used carefully in dogs that are already ill, vomiting, having diarrhea, or not eating well, because those signs can overlap with drug toxicity. It is also generally avoided in pregnant or nursing animals. Since this medication is used off label in dogs, your vet’s instructions may differ from human labeling and should be followed closely.

A practical rule for pet parents is this: before starting any new medication, supplement, or over-the-counter product, ask your vet whether it could affect mitotane safety or monitoring. That quick check can prevent confusion and reduce the risk of complications.