Mitotane dosing

Compazine 10 mg PO/IV 30 minutes before each dose of mitotane if needed... 

Mitotane—if well-tolerated, dose may be doubled on day 3 then, from day 5 onwards, may increase dose by 500 mg every 2-3 days until maximum tolerated dose (8-12 grams daily) has been reached glucocorticoid and mineralocorticoid replacement necessary to prevent adrenal insufficiency increased steroid doses may be needed at times of physiologic stress... 

Mitotane (o,p-DDD) -adrenocortical cytotoxin -nausea and vomiting -CNS toxicity—lethargy, vertigo, sedation, dizziness -adrenal insufficiency—must use replacement doses of mineralocorticoids and glucocorticoids -diarrhea -fever -wheezing -flushing... 

Mitotane (Figure 39-5), a drug related to the DDT class of insecticides, has a nonselective cytotoxic action on the adrenal cortex in dogs and to a lesser extent in humans. This drug is administered orally in divided doses up to 12 g daily. About one third of patients with adrenal carcinoma show a reduction in tumor mass. In 80% of patients, the toxic effects are sufficiently severe to require dose reduction. These... 

About 40% of a single oral dose of mitotane is ab-sorbed. Only 10 to 2S% is excreted in urine as an unidentilied metab olite. and 60% is excreted unchanged in tieccs. Must of the remainder is stored in fatty tissues of the body. 

Mitotane is an antineoplastic agent. The primary action is on the adrenal cortex. The production of adrenal steroids is reduced. The biochemical mechanism of action is nnknown. Data suggest that the drug modifies the peripheral metabolism of steroids and directly suppresses the adrenal cortex. Use of mitotane alters the peripheral metabolism of cortisol, even though plasma levels of corticosteroids do not fall. The drug causes increased formation of 6-beta-hydroxycortisol. Mitotane, a chlorophenothane (DDT) analog with antineoplastic properties (1 to 6 g p.o. daily in divided doses), is used in the treatment of inoperable adrenocortical cancer. 

Approximately 40% of mitotane is absorbed after oral administration. After daily doses of 5 to 15 g, concentrations of 10 to 90 J.g/mL of unchanged drug and 30 to 50 pg/mL of a metabolite are present in the blood. After discontinuation of therapy, plasma concentrations of mitotane are still measurable for 6 to 9 weeks. Although the drug is found in all tissues, fat is the primary site of storage. A water-soluble metabolite of mitotane is found in the urine approximately 25% of an oral or parenteral dose is recovered in this form. About 60% of an oral dose is excreted unchanged in the stool. 

Mitotane (Lysodren) is administered in initial daily oral doses of 2 to 6 g, usually given in three or four divided portions, but the maximal tolerated dose may vary from 2 to 16 g per day. Treatment should be continued for at least 3 months if beneficial effects are observed, therapy should be maintained indefinitely. Spironolactone should not be administered concomitantly because it interferes with the adrenal suppression produced by mitotane. 

Althongh the administration of mitotane produces anorexia and nausea in approximately 80% of patients, somnolence and lethargy in abont 34%, and dermatitis in 15 to 20%, these effects do not contraindicate the use of the drug at lower doses. Because this drug damages the adrenal cortex, administration of adrenocorticosteroids is indicated, particularly in patients with evidence of adrenal insufficiency, shock, or severe tranma. 

Mitotane (lysodren) is administered in initial daily oral doses of 2-6 g, usually given in 3 or 4 divided portions, but the maximal tolerated dose may vary from 2 to 16 g/day. Treatment should be continued for at least 3 months if beneficial effects are observed, therapy should be maintained indefinitely. Spironolactone should not be administered concomitantly, since it interferes with the adrenal suppression produced by mitotane. Treatment with mitotane is indicated for the palliation of inoperable adrenocortical carcinoma, producing symptomatic benefit in 30—50% of such patients. Although the administration of mitotane produces anorexia and nausea in 80% of patients, somnolence and lethargy in 34%, and dermatitis in 15—20%, these effects do not contraindicate the use of the drug at lower doses. Since this drug damages the adrenal cortex, administration of corticosteroids is indicated, particularly in patients with evidence of adrenal insufficiency, shock, or severe trauma. 

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