Trilostane
Trilostane is a synthetic steroid analog and currently the **standard of care** for managing pituitary-dependent and adrenal-dependent hyperadrenocorticism (Cushing's syndrome) in dogs. Unlike older therapies such as mitotane, which cause targeted necrosis of the adrenal cortex, trilostane works by reversibly inhibiting steroidogenesis. This makes it generally safer and more predictable, though careful monitoring is still required to prevent iatrogenic hypoadrenocorticism (Addison's disease). **Key Clinical Uses:** * **Dogs:** Pituitary-dependent and adrenal-dependent hyperadrenocorticism; Alopecia X (especially in Pomeranians and Alaskan Malamutes). * **Cats:** Feline pituitary-dependent hyperadrenocorticism (off-label). * **Horses:** Equine hyperadrenocorticism / Pituitary Pars Intermedia Dysfunction (PPID) (off-label, though pergolide is more commonly the first-line treatment for PPID). > **Clinical Pearl:** When used in dogs with adrenal tumors, trilostane will control the clinical signs of Cushing's but will *not* shrink the tumor. In fact, the adrenal glands may undergo compensatory hypertrophy and increase in size during treatment.
Mechanism: Trilostane acts as a competitive, reversible, and dose-dependent inhibitor of the enzyme **3-beta hydroxysteroid dehydrogenase (3ฮฒ-HSD)**. * **Pathway Blockade:** Pregnenolone โ **[3ฮฒ-HSD Blocked]** โ Progesterone * By blocking this crucial early step in the adrenal steroidogenesis pathway, trilostane effectively reduces the downstream synthesis of **cortisol**, **aldosterone**, and **adrenal androgens**. * Because the inhibition is competitive and reversible, the suppressive effects on cortisol production wane within 10 to 20 hours, necessitating daily or twice-daily dosing.
Dosing by species
- Hyperadrenocorticism ยท 7 mg/kg/day divided and given twice daily ยท PO ยท q12h ยท Doses of up to 60 mg per cat per day have been used.
- Hyperadrenocorticism ยท 15 mg (total dose) PO once daily to 60 mg (total dose) PO q12h ยท PO ยท q24h to q12h ยท Titrate dose with ACTH stimulation tests. Cats typically remain diabetic despite clinical improvement.
- Hyperadrenocorticism ยท 10-30 mg/cat p.o. q12-24h ยท PO ยท q12h to q24h ยท Lifelong ยท Give with food.
- Equine Cushing's syndrome ยท 0.4-1 mg/kg (total dose 120-240 mg) PO once daily ยท PO ยท q24h
- Hyperadrenocorticism (HAC) - Label Dose ยท 2.2-6.7 mg/kg PO once a day with food ยท PO ยท q24h ยท Adjust dose based on ACTH stimulation test 10-14 days post-initiation. May require twice daily dosing if clinical signs are not controlled for the full day.
- Hyperadrenocorticism (HAC) - Alternative Protocol ยท 2-10 mg/kg PO once daily ยท PO ยท q24h ยท Doses of up to 50 mg/kg/day divided twice daily have been given. Adjust based on ACTH stim test 4-6 hours post-dose.
- Hyperadrenocorticism (HAC) - Low Dose Protocol ยท 1 mg/kg PO once daily ยท PO ยท q24h ยท Recheck in 1 week. Adjust based on clinical response, UCCR, and ACTH stimulation test.
- Alopecia X (Alaskan Malamutes) ยท 3-3.6 mg/kg PO twice a day ยท PO ยท q12h ยท 4-6 months
Routes of administration
Contraindications
- Hypersensitivity to trilostane
- Pregnancy (reduces progesterone synthesis)
- Use with caution in patients with renal impairment
- Use with caution in patients with hepatic impairment
- Renal insufficiency
- Hepatic insufficiency
Adverse effects
- Lethargy
- Inappetence
- Vomiting
- Diarrhea
- Mild electrolyte abnormalities (hyponatremia, hyperkalemia)
- Iatrogenic hypoadrenocorticism (Addisonian crisis)
- Adrenal necrosis (rare but potentially fatal)
- Mild gastrointestinal signs
- Mild increases in serum potassium, bilirubin, and calcium
- Clinical hypoadrenocorticism (Addisonian crisis)
- Adrenal necrosis
- Adrenal hyperplasia (with prolonged treatment)
- Prolonged adrenal suppression after drug withdrawal
Drug interactions
- ACE Inhibitors (e.g., benazepril, enalapril) ยท Could increase risk for hyperkalemia
- Aminoglutethimide ยท May potentiate the effects of trilostane and lead to hypoadrenocorticism
- Ketoconazole ยท May potentiate the effects of trilostane and lead to hypoadrenocorticism
- Mitotane ยท May potentiate the effects of trilostane and lead to hypoadrenocorticism ยท major
- Potassium-sparing diuretics (e.g., spironolactone) ยท Could increase risk for hyperkalemia
- Potassium supplements / High potassium foods ยท Could increase risk for hyperkalemia
- Itraconazole ยท Concurrent suppression of adrenal function ยท moderate
Monitoring
- Clinical signs (water intake, urination, appetite, energy level)
- Adverse effects (vomiting, diarrhea, lethargy)
- Serum electrolytes (Sodium and Potassium)
- Urinalysis (Specific gravity, glucose, urine cortisol:creatinine ratio [UCCR])
- ACTH stimulation tests (conducted 4-6 hours post-pill)
- Clinical signs (water intake, urination, appetite, hair coat)
- ACTH stimulation test (3 hours post-pill)
- Pre-pill baseline cortisol
- Serum electrolytes (potassium, calcium)
- Liver parameters (bilirubin)
Overdose
Acute overdoses are unlikely to be life-threatening, and severe clinical signs are not typically expected immediately. * **Monitoring:** Assess blood pressure, hydration status, and electrolyte balance (Na/K). * **Treatment:** If the animal is stressed or showing signs of hypoadrenocorticism, consider administering exogenous corticosteroids short-term. * Because the drug's effects are relatively short-lived, monitoring of uncomplicated patients is usually only required for a few days post-ingestion.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.