The starting dose for the treatment of hyperadrenocorticism in dogs is 1.0-3.0 mg/lb (2.2-6.7 mg/kg) once a day based on body weight and capsule size. VETORYL Capsules should be administered once daily in the morning with food. Giving with food will significantly increase the rate and extent of absorption of Vetoryl.

Starting dose

Dogs over 132 pounds (60 kg) should be administered the appropriate combination of capsules.

After approximately 10-14 days at this dose, re-examine the dog and conduct a 4-6 hour post-dosing ACTH stimulation test.

If physical examination is acceptable, take action according to the following Table.

Action at 10-14 day evaluation

Combinations of capsule sizes should be used to slowly increase the once daily dose.

Individual dose adjustments and close monitoring are essential. Re-examine and conduct an ACTH stimulation test 10-14 days after every dose alteration. Care must be taken during dose increases to monitor the dog's clinical signs and serum electrolyte concentrations. Once daily administration is recommended. However, if clinical signs are not controlled for the full day, twice daily dosing may be needed using combinations of capsule sizes to slowly increase the dose. For once daily doses up to 90 mg, increase the total daily dose by 30 mg and divide into 2 doses given 12 hours apart. For once daily doses ?120 mg, increase the total daily dose by 60 mg and divide into 2 doses given 12 hours apart.

Long Term Monitoring

Once an optimum dose of VETORYL Capsules has been reached, re-examine the dog at 30 days, 90 days and every 3 months thereafter. At a minimum, this monitoring should include a thorough history and physical examination, ACTH stimulation test (conducted 4-6 hours after VETORYL Capsule administration), and serum biochemical tests (with particular attention to electrolytes, renal and hepatic function). A post-ACTH stimulation test resulting in a cortisol of < 1.45 µg/dL (< 40 nmol/L), with or without electrolyte abnormalities, may precede the development of clinical signs of hypoadrenocorticism. Good control is indicated by favorable clinical signs as well as post-ACTH serum cortisol of 1.45-9.1 µg/dL (40-250 nmol/L).

If the ACTH stimulation test is < 1.45 µg/dL (< 40 nmol/L) and/or if electrolyte imbalances characteristic of hypoadrenocorticism (hyperkalemia and hyponatremia) are found, VETORYL Capsules should be temporarily discontinued until recurrence of clinical signs consistent with hyperadrenocorticism and test results return to normal (1.45-9.1 µg/dL or 40-250 nmol/L). VETORYL Capsules may then be re-introduced at a lower dose.

Owners should be instructed to stop therapy and contact their veterinarian immediately in the event of adverse reactions or unusual developments.

Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian

CONTRAINDICATIONS:

The use of VETORYL Capsules is contraindicated in dogs that have demonstrated hypersensitivity to trilostane.

Do not use VETORYL Capsules in animals with primary hepatic disease or renal insufficiency.

Do not use in pregnant dogs. Studies conducted with trilostane in laboratory animals have shown teratogenic effects and early pregnancy loss.

WARNINGS:

In case of overdosage, symptomatic treatment of hypoadrenocorticism with corticosteroids, mineralocorticoids and intravenous fluids may be required.

Angiotensin converting enzyme (ACE) inhibitors should be used with caution with VETORYL Capsules, as both drugs have aldosterone-lowering effects which may be additive, impairing the patient's ability to maintain normal electrolytes, blood volume and renal perfusion. Potassium sparing diuretics (e.g. spironolactone) should not be used with VETORYL Capsules as both drugs have the potential to inhibit aldosterone, increasing the likelihood of hyperkalemia.

HUMAN WARNINGS:

Keep out of reach of children. Not for human use.

Wash hands after use. Do not empty capsule contents and do not attempt to divide the capsules. Do not handle the capsules if pregnant or if trying to conceive. Trilostane is associated with teratogenic effects and early pregnancy loss in laboratory animals. In the event of accidental ingestion/overdose, seek medical advice immediately and take the labeled container with you.

PRECAUTIONS:

Hypoadrenocorticism can develop at any dose of VETORYL Capsules. In some cases, it may take months for adrenal function to return and some dogs never regain adequate adrenal function.

A small percentage of dogs may develop corticosteroid withdrawal syndrome within 10 days of starting treatment. This phenomenon results from acute withdrawal of circulating glucocorticoids; clinical signs include weakness, lethargy, anorexia, and weight loss¹. These clinical signs should be differentiated from an early hypoadrenocortical crisis by measurement of serum electrolyte concentrations and performance of an ACTH stimulation test. Corticosteroid withdrawal syndrome should respond to cessation of VETORYL Capsules (duration of discontinuation based on the severity of the clinical signs) and restarting at a lower dose.

Mitotane treatment will reduce adrenal function. Experience in foreign markets suggests that when mitotane therapy is stopped, an interval of at least one month should elapse before the introduction of VETORYL Capsules. It is important to wait for both the recurrence of clinical signs consistent with hyperadrenocorticism, and a post-ACTH cortisol level of > 9.1 µg/dL (> 250 nmol/L) before treatment with VETORYL Capsules is initiated. Close monitoring of adrenal function is advised, as dogs previously treated with mitotane may be more responsive to the effects of VETORYL Capsules.

The use of VETORYL Capsules will not affect the adrenal tumor itself. Adrenalectomy should be considered as an option for cases that are good surgical candidates.

The safe use of this drug has not been evaluated in lactating dogs and males intended for breeding.

Adverse Reactions:

The most common adverse reactions reported are poor/reduced appetite, vomiting, lethargy/dullness, diarrhea, and weakness. Occasionally, more serious reactions, including severe depression, hemorrhagic diarrhea, collapse, hypoadrenocortical crisis or adrenal necrosis/rupture may occur, and may result in death.

Dog Owners should be aware that the most common adverse reactions may include: an unexpected decrease in appetite, vomiting, diarrhea, or lethargy and should receive the Client Information Sheet with the prescription. Owners should be informed that control of hyperadrenocorticism should result in resolution of polyphagia, polyuria and polydipsia. Serious adverse reactions associated with this drug can occur without warning and in rare situations result in death. Owners should be advised to discontinue VETORYL Capsules and contact their veterinarian immediately if signs of intolerance are observed. Owners should be advised of the importance of periodic follow-up for all dogs during administration of VETORYL Capsules.

Storage: Store at controlled room temperature 25°C (77°F) with excursions between 15°-30°C (59°-86°F) permitted.

How Supplied: VETORYL Capsules are available in 10, 30, 60 and 120 mg strengths, packaged in aluminum foil blister cards of 10 capsules, with 3 cards per carton.