Doses - MITOTANE, O, P' - DDD
Dogs: 
For medical treatment of pituitary-dependent hyperadrenocorticism (bilateral adrenal hyperplasia): Note: The information provided below (in "a & b") is a synopsis of the authors'treatment protocol. It is strongly recommended to refer to the original references and read theentire discussion before instituting therapy for the first time. a) Initiate therapy at home (preferably on a Saturday): 50 mg/kg divided twice a day PO.
Do not give glucocorticoids, but owner should have a small supply of prednisolone.
Give until one of the following occurs: Polydipsic dogs consume less than 60 ml/kg/dayof water; dogs' with excellent appetite takes 10-30 minutes longer than before mitotanetherapy to consume meals (feed two small meals twice daily); dog vomits, is listless, orhas diarrhea. Beginning on 3rd day of therapy, contact owner daily to monitor thesituation and encourage. If dog develops GI upset 3-4 days after starting therapy;evaluate and either temporarily halt therapy or divide dosage further.
After 8-9 days after therapy initiated, the dog should be evaluated and history andphysical repeated, ACTH response test, BUN, serum sodium and potassium redone. Ifthe dog has responded clinically, stop mitotane until ACTH response test can be evaluated. If the response test yields normal or high cortisol values, mitotane is continued(generally for 3-7 days). Repeat ACTH response test every 7-10 days until a low post-ACTH cortisol level is obtained. Most dogs respond during the first 7-10 days andnearly all respond by the 16th day of therapy.
Maintenance therapy: Dogs who have responded to mitotane within 10 days ofinitiation receive 25 mg/kg every 7 days. Recheck ACTH response every 1-3 months.
Those taking longer than 10 days to respond, receive 50 mg/kg weekly. If ACTH-stimulated cortisol levels begin to increase, mitotane dosage should be increased. Dogs with recurrent signs and symptoms of PDH or post ACTH cortisol values of > 5micrograms/dl, should undergo daily therapy as outlined above. These animals shouldalso be evaluated for other conditions (e.g., renal disease, diabetes mellitus). Shouldanorexia and listlessness be seen with low plasma cortisol levels, reduce dosage.(Feldman 1989)
b) 40 - 50 mg/kg/day with food until serum cortisol reaches the normal resting range(usually takes 7-10 days). Once adrenal reserve is appropriately reduced, continue at 50mg/kg/week in 2-3 divided dosages. See full reference for more specific details regarding dosage adjustments and monitoring of therapy. (Kintzer and Peterson 1995)
For palliative medical treatment of adrenal carcinomas or medical treatment of adrenal adenomas:
a) Initially, 50 - 75 mg/kg PO in daily divided doses for 10-14 days. May supplement withpredniso(lo)ne at 0.2 mg/kg/day. Stop therapy and evaluate dog if adverse effects occur.
After initial therapy run ACTH-stimulation test (do not give predniso(lo)ne the morningof the test). If basal or post-ACTH serum cortisol values are decreased, but still abovethe therapeutic end-point (<1 micrograms/dl), repeat therapy for an additional 7-14 daysand repeat testing.
If post-ACTH serum cortisol values remain greatly elevated or unchanged, increasemitotane to 100 mg/kg/day and repeat ACTH-stimulation test at 7-14 day intervals. Ifcontinues to remain greatly elevated, increase dosage by 50 mg/kg/day every 7-14 daysuntil response occurs or drug intolerance ensues. Adjust dosage as necessary as patienttolerates or ACTH-responsive dictates.
Once undetectable or low-normal post-ACTH cortisol levels are attained, continuemitotane at 100 - 200 mg/kg/week in divided doses with glucocorticoid supplementation(predniso(lo)ne 0.2 mg/kg/day). Repeat ACTH-stimulation test in 1-2 months. continueat present dose if cortisols remain below 1 micrograms/dl. Should cortisols increase to 1- 4 micrograms/dl, increase maintenance dose by 50%. If basal or post-ACTH cortisolsgo above 4 micrograms/dl, restart daily treatment (50 - 100 mg/kg/day) as outlinedabove. Once patient is stabilized, repeat ACTH-stimulation tests at 3-6 month intervals.(Kintzer and Peterson 1989)
Monitoring Parameters -
Initially and prn (see doses above):
Client Information - Clients must be clearly instructed in the adverse effects of the drug and thesymptoms of acute hypoadrenocorticism. Because of the potential severe toxicity associated withthis agent, clients should be instructed to wash their hands after administering and to keep thetablets out of reach of children or pets.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times - Veterinary-Approved Products: None