Trilostane Capsules

Trilostane

5mg/10mg/ 20mg/30mg/60mg

Capsules

Adrenocortical suppressant for oral use in dogs only.

DESCRIPTION:

Trilostane Capsules are available in 5 sizes (5, 10, 20, 30, and 60 mg) for oral administration based on body weight. Trilostane (4α,5α-epoxy-17β-hydroxy-3-oxoandrostane-2α-carbonitrile) is an orally active synthetic steroid analogue that selectively inhibits 3 β-hydroxysteroid dehydrogenase in the adrenal cortex, thereby inhibiting the conversion of pregnenolone to progesterone. This inhibition blocks production of glucocorticoids and to a lesser extent, mineralocorticoids and sex hormones while steroid precursor levels increase. The structural formula is:

INDICATIONS:

Trilostane Capsules are indicated for the treatment of pituitary-dependent and adrenal-dependent hyperadrenocorticism in dogs.

DOSAGE AND ADMINISTRATION:

1. Starting dose

The starting dose for the treatment of hyperadrenocorticism in dogs is 1-3 mg/lb (2.2-6.7 mg/kg) once a day. Start with the lowest possible dose based on body weight and available combinations of capsule sizes. Trilostane Capsules should be administered with food.

2. Action at 10-14 day evaluation (Table 1)

After approximately 10-14 days at this dose, re-examine the dog and conduct a 4-6 hour post-dosing ACTH stimulation test and serum biochemical tests (with particular attention to electrolytes, and renal and hepatic function). If physical examination is acceptable, take action according to Table 1.

Owners should be instructed to stop therapy and contact their veterinarian immediately in the event of adverse reactions such as vomiting, diarrhea, lethargy, poor/reduced appetite, weakness, collapse or any other unusual developments. If these clinical signs are observed, conduct an ACTH stimulation test and serum biochemical tests (with particular attention to electrolytes, and renal and hepatic function).

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

3. Individual dose adjustments and close monitoring are essential

Re-examine and conduct an ACTH stimulation test and serum biochemical tests (with particular attention to electrolytes, and renal and hepatic function) 10-14 days after every dose alteration. Care must be taken during dose increases to monitor the dog's clinical signs.

Once daily administration is recommended. However, if clinical signs are not controlled for the full day, twice daily dosing may be needed. To switch from a once daily dose to a twice daily dose, the total daily dose should be divided into 2 portions given 12 hours apart. It is not necessary for the portions to be equal. If applicable, the larger dose should be administered in the morning and the smaller dose in the evening. For example, a dog receiving 90 mg would receive 60 mg in the morning, and 30 mg in evening.

4. Long term monitoring

Once an optimum dose of Trilostane 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.

An ACTH stimulation test (conducted 4-6 hours after Trilostane Capsule administration) - 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.

Serum biochemical tests (with particular attention to electrolytes, and renal and hepatic function).

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, Trilostane Capsules should be temporarily discontinued until recurrence of clinical signs consistent with hyperadrenocorticism and ACTH stimulation test results return to normal (1.45-9.1 µg/dL or 40-250 nmol/L).

Trilostane Capsules may then be re-introduced at a lower dose.

CONTRAINDICATIONS:

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

Do not use Trilostane 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:

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

All dogs should undergo a thorough history and physical examination before initiation of therapy with Trilostane Capsules. Other conditions, such as primary hepatic and/or renal disease should be considered when the patient is exhibiting signs of illness in addition to signs of hyperadrenocorticism (e.g. vomiting, diarrhea, poor/reduced appetite, weight loss, and lethargy). Appropriate laboratory tests to establish hematological and serum biochemical baseline data prior to, and periodically during, administration of Trilostane Capsules should be considered.

Owners should be advised to discontinue therapy immediately and contact their veterinarian if signs of potential drug toxicity are observed.

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 Trilostane 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 Trilostane 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.

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.

INFORMATION FOR DOG OWNERS:

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 some cases result in death

Owners should be advised to discontinue Trilostane Capsules and contact their veterinarian immediately if signs of intolerance such as vomiting, diarrhea, lethargy, poor/reduced appetite, weakness, or collapse are observed. Owners should be advised of the importance of periodic follow-up for all dogs during administration of Trilostane Capsules.

CLINICAL PHARMACOLOGY:

Trilostane absorption is enhanced by administration with food. In healthy dogs, maximal plasma levels of trilostane occur within 1.5 hours, returning to baseline levels within twelve hours, although large inter-dog variation occurs. There is no accumulation of trilostane or its metabolites over time.

STORAGE INFORMATION:

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

Generic medication and its counterpart to have the same active ingredients, strength, quality, route of administration, and safety standards.All of our products are produced in GMP factories, Your pet’s health is our top priority.

This summary contains important information about Trilostane. You should read this information before you start giving your dog Trilostane and review it each time the prescription is refilled as there may be new information. This sheet is provided only as a summary and does not take the place of instructions from your veterinarian. Talk with your veterinarian if you do not understand any of this information or if you want to know more about Trilostane.

What is Trilostane?

Trilostane Capsules contain an adrenosuppressant drug that is used to treat hyperadrenocorticism in dogs.

Trilostane Capsules are a prescription drug for dogs.

Hyperadrenocorticism (also known as Cushing's disease) is a condition in which excess levels of the hormone cortisol are produced. Cortisol is normally released from the adrenal gland into the bloodstream at times of stress.

In dogs with hyperadrenocorticism, the level of cortisol produced is excessive and, if left untreated, becomes incapacitating.

Characteristic signs are:

• Passing large quantities of urine
• Frequent urination and possible incontinence
• Excessive drinking
• Ravenous appetite
• Lethargy or decreased activity
• Excessive panting
• Pot belly
• Thin skin
• Hair loss or recurrent skin diseases
• Muscle wasting

Your dog may not necessarily display all of these signs.

What should I talk to my veterinarian about before giving Trilostane Capsules?

Periodic follow-up and laboratory testing are important for continual safe use of Trilostane Capsules. Talk with your veterinarian about how often your dog will need to be examined.

Talk to your veterinarian about:

• What tests might be done before Trilostane Capsules are prescribed.
• How often your dog may need to be examined by your veterinarian.
• The risks and benefits of using Trilostane Capsules.

Tell your veterinarian if your dog has ever had the following medical problems:

• Liver disease
• Kidney disease

Tell your veterinarian about:

• Any other medical problems or allergies that your dog has now or has had.
• If your dog is pregnant, nursing or if you plan to breed your dog.
• Any medications your dog is taking, including over-the-counter products and nutritional supplements.

What are the possible side effects that may occur in my dog during therapy?

Trilostane Capsules, like other drugs, may cause some side effects. Serious side effects have been reported in dogs taking Trilostane Capsules. Serious side effects can occur with or without warning and result in death.

Side effects generally involve an over suppression of the adrenal glands (hypoadrenocorticism, also known as Addison's Disease). Look for the following side effects that may indicate your dog is having a problem with Trilostane Capsules or may have another medical problem:

• Depression, lethargy or decrease in activity
• Change in bowel movements (such as diarrhea or loose stools)
• Vomiting
• Stops eating or loses all interest in food
• Weakness and collapse

It is important to stop therapy and contact your veterinarian immediately if you think your dog has a medical problem or side effect from Trilostane Capsule therapy. If you have additional questions about possible side effects, talk to your veterinarian.

As Trilostane Capsules control the hyperadrenocorticism, there should be a decrease in food and water consumption to normal levels. There should also be resolution of excess urination. If, however, there is a dramatic decrease in appetite or your dog stops drinking water, it could be an indication of a side effect requiring treatment.

What drug interactions should be noted when using Trilostane?

When using Trilostane, veterinarians should be mindful of potential drug interactions that could affect its efficacy or safety. Here are some notable drug interactions to consider:

 ACE Inhibitors:

• Trilostane should be used with caution in dogs concurrently receiving angiotensin-converting enzyme (ACE) inhibitors. The combination may affect electrolyte balance, especially potassium levels.

 Potassium-Sparing Diuretics:

• Similar to ACE inhibitors, caution is advised when Trilostane is used alongside potassium-sparing diuretics. This combination may lead to elevated potassium levels.

Mitotane:

• Dogs that have recently been treated with mitotane, another medication used in Cushing's disease, should wait at least one month after discontinuing mitotane before starting Trilostane therapy.

It's crucial for veterinarians to be aware of the dog's complete medication history and inform pet owners about potential interactions. Close monitoring of electrolyte levels, especially potassium, may be necessary when Trilostane is administered concurrently with certain medications. Regular veterinary check-ups and communication with the veterinarian are essential to ensure the dog's well-being during treatment.

What if I miss giving my pet the medication or my shipment is late?

If you miss a dose, skip the dose you missed and give it at the next scheduled time, and return to the regular dosing schedule. Never give your pet two doses at once or give extra doses.

Do not stop this drug without consulting your veterinarian.

Is there any monitoring that needs to be done with this medication?

You should monitor your pet closely for adverse effects. After starting the medication, frequent and regular rechecks with your veterinarian are important. Adrenocorticotropic hormone (ACTH) stimulation tests and other laboratory tests will be needed to monitor for adverse effects, efficacy, and dose appropriateness.

What should I do in case of emergency?

In the case of an Addisonian crisis, glucocorticoids should be administered immediately, followed by veterinary care. Your veterinarian should provide you with an emergency supply of glucocorticoids as a precaution.

If you suspect an overdose or an adverse reaction to the medication, call your veterinary office immediately. If they are not available, follow their directions in contacting an emergency facility.