trilostane

Action and Spectrum

Actions and spectrum: 

Action: 

• trilostane inhibits the activity of 3-beta-hydroxysteroid dehydrogenase, an enzyme responsible for conversion of pregnenolone to progesterone and 17-hydroxypregnenolone to 17-hydroxyprogesterone. This inhibition reduces the production of cortisol and other glucocorticoid hormones in the adrenal glands. 

Spectrum: 

• trilostane is primarily used in veterinary medicine for the treatment of Cushing’s syndrome in dogs. It is not typically used in human medicine. 
• The medication helps to control the excessive production of cortisol and alleviate the symptoms associated with Cushing’s syndrome in dogs, including urination, increased thirst, appetite and muscle weakness. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Rashes 

Tingling 

Granulocytopenia 

Mouth swelling 

Flushing 

Black Box Warning

Black Box Warning: 

It does not have a black box warning associated with trilostane. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: trilostane should not be used in dogs that have shown hypersensitivity or allergic reactions to the drug. 
• Liver or kidney disease: The drug gets metabolized by liver and excreted through the kidneys, so impaired organ function can affect its clearance and increase the risk of side effects. 
• Pregnancy and Lactation: The safety of trilostane in pregnant or lactating dogs has not been well established, so it is not recommended during these periods. 
• Hypoadrenocorticism: trilostane is used to treat Cushing’s syndrome, which results from an overproduction of cortisol. It should not be administered in dogs with primary hypoadrenocorticism (Addison’s disease), a condition where the adrenal glands produce insufficient cortisol.

Caution: 

• Dosing Accuracy: trilostane must be accurately dosed to avoid excessive cortisol reduction, which can lead to hypoadrenocorticism (Addison’s disease), or inadequate reduction, which may not effectively manage Cushing’s syndrome. 
• Monitoring: Regular monitoring of your dog’s clinical signs and laboratory values, such as cortisol levels, is crucial to adjust the trilostane dose as needed and ensure its effectiveness. 
• Stress and Other Illnesses: Dogs with Cushing’s syndrome may be more susceptible to stress or other illnesses. It is important to monitor your dog for signs of illness or stress and consult your veterinarian, if necessary, as adjustments to the trilostane dose may be required. 
• Concurrent Medications: Inform your veterinarian about all medications your dog is taking, as some drugs may interact with trilostane, potentially affecting its efficacy or safety. 
• Adverse Effects: Watch for potential side effects, which can include gastrointestinal upset, lethargy, weakness, and decreased appetite. Report any adverse reactions to your veterinarian. 
• Duration of Treatment: trilostane is typically used for the long-term management of Cushing’s syndrome, and discontinuing the medication abruptly can lead to an increase in cortisol production. If you plan to discontinue trilostane, consult your veterinarian for guidance on tapering the dose.

Comorbidities: 

• Urinary Tract Infections (UTIs): Dogs with Cushing’s syndrome is more prone to UTIs due to weakened immune function and increased water consumption. 
• Muscle Weakness and Atrophy: Cushing’s syndrome can lead to muscle weakness and atrophy in dogs. 
• Skin Issues: Skin problems like thinning, bruising, and delayed wound healing can be comorbid with Cushing’s syndrome. 
• Potassium Depletion: Low potassium levels can occur, leading to muscle weakness or other issues. 
• Hypertension (High Blood Pressure): Some dogs with Cushing’s syndrome may develop hypertension, which can have various health implications. 
• Pancreatitis: There is a potential link between Cushing’s syndrome and an increased risk of pancreatitis. 
• Heart Disease: Cushing’s syndrome can affect the cardiovascular system, potentially leading to heart disease. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: not assigned 

Lactation: excreted into human milk: unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

trilostane is a medication used in veterinary medicine to treat Cushing’s syndrome, a condition characterized by excessive production of cortisol (a stress hormone) in dogs. trilostane works by inhibiting an enzyme called 3-beta hydroxysteroid dehydrogenase, which is involved in cortisol production.

By blocking this enzyme, trilostane reduces cortisol levels, alleviating the symptoms associated with Cushing’s syndrome. This medication helps restore hormonal balance and improve the quality of life for dogs. It is typically administered orally and requires close monitoring by a veterinarian to adjust the dosage and ensure its effectiveness while minimizing potential side effects.  

Pharmacodynamics: 

The pharmacodynamics of trilostane is primarily related to its mechanism of action in inhibiting cortisol production. trilostane exerts its effects by blocking the activity of the enzyme 3-beta hydroxysteroid dehydrogenase. This plays a crucial role in the synthesis of cortisol, a stress hormone produced by adrenal glands. By inhibiting 3-beta hydroxysteroid dehydrogenase, trilostane reduces the formation of cortisol, leading to decreased cortisol levels in the body.

trilostane is commonly used to manage Cushing’s syndrome (hyperadrenocorticism) in dogs. In this condition, the adrenal glands overproduce cortisol, resulting in various clinical signs such as increased thirst, urination, and appetite, as well as muscle weakness and skin problems. trilostane helps normalize the excess cortisol production, alleviating these symptoms and improving the dog’s overall health and well-being.  

Pharmacokinetics: 

Absorption 

trilostane is administered orally and is absorbed from the gastrointestinal tract. Its absorption may be variable among individuals. 

Distribution 

trilostane is distributed throughout the body via the bloodstream. It is likely to distribute to various tissues and organs. 

Metabolism 

trilostane undergoes hepatic metabolism, where it may be metabolized by enzymes in the liver. The primary metabolites are 3-alpha, 3-beta, and 17-beta-sulfates of trilostane. 

Elimination and excretion 

trilostane and its metabolites are excreted primarily through the urine. It is important to note that trilostane’s elimination half-life can vary between individuals. 

Adminstartion

Administration: 

• Dosing: trilostane is usually given once daily. The exact dose and dosing schedule should be determined by a healthcare provider or veterinarian based on the patient’s condition and needs. 
• With Food: In most cases, trilostane is administered with food. This can help improve its absorption and reduce the likelihood of gastrointestinal upset. 
• Monitoring: Regular monitoring of the patient’s condition is essential, especially when trilostane is used to manage conditions like Cushing’s syndrome in dogs. This may involve periodic blood tests to assess cortisol levels. 
• Adherence: It is important to ensure strict adherence to the prescribed treatment regimen. If you miss a dose, do not double up on the next dose. Follow the regular schedule or consult your healthcare provider or veterinarian for guidance. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: trilostane 

Pronounced: (try-lo-stane)  

Why do we use trilostane? 

trilostane is commonly prescribed by veterinarians to manage the symptoms of Cushing’s syndrome in dogs. This condition can cause a range of clinical signs, including excessive drinking and urination, increased appetite, hair loss, and muscle weakness. trilostane helps normalize cortisol levels and alleviate these symptoms.

trilostane doesn’t cure Cushing’s syndrome, but it is effective in controlling and reducing the clinical signs associated with the disease. Cushing’s syndrome often requires lifelong management, and trilostane is a key medication used in this ongoing treatment. Veterinary monitoring is crucial to adjust the dosage as needed and ensure the dog’s health.