Dosing & Uses
Dosage Forms & Strengths
tablet
- 500mg
Adrenal Carcinoma
Indicated for inoperable adrenal cortical carcinoma of both functional and nonfunctional types
Initial: 2-6 g/day PO divided q6-8hr, THEN
Increase incrementally to 9-10 g/day divided q6-8hr
Maximum tolerated dose varies from 2-16 g/day, usually 9-10 g/day
The highest doses used in clinical trials were 18-19 g/day
Cushing's Syndrome (Off-label)
Initial: 1.5 g PO divided q6-8hr; not to exceed 3 g PO q8hr
Maintenance: 500 mg 2 x/week to 2 g/day
Administration
All tumor tissue should be surgically removed before administration
Monitor
Growth of adrenal cortex metastatic lesion
Hepatic Impairment
May need to decrease dose in patients with liver disease
Dosage Forms & Strengths
tablet
- 500mg
Adrenocortical Carcinoma (Off-label)
1-2 g/day PO in divided dose; may increase gradually not to exceed 5-7 g/day
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Nausea (39%)
Vomiting (37%)
Lethargy/somnolence (25%)
Anorexia (24%)
Vertigo (15%)
Skin rash (15%)
Diarrhea (13%)
Weakness (12%)
Frequency Not Defined
Eye: Visual blurring, diplopia, lens opacity, toxic retinopathy
Genitourinary: Hematuria, hemorrhagic cystitis, and albuminuria
Cardiovascular: Hypertension, orthostatic hypotension, and flushing
Generalized aching and hyperpyrexia
Decreased protein bound iodine
Postmarketing Reports
Blood and lymphatic system disorders: Neutropenia
Endocrine disorders: Growth retardation, hypothyroidism
Psychiatric disorders: Confusional state
Nervous system disorders: Neuropsychological disturbance, dysarthria, headache, ataxia, mental impairment
Eye disorders: Maculopathy
Hepatobiliary disorders: Hepatitis, elevation of liver enzymes
Reproductive system and breast disorders: Gynecomastia, ovarian macrocysts
Warnings
Black Box Warnings
Administered under the supervision of an experienced cancer chemotherapy physician in a facility equipped to manage complications
The drug suppresses adrenal function; stop therapy temporarily after shock or severe trauma and administer exogenous steroids since the drug depressed adrenal function may not immediately return
Contraindications
Hypersensitivity
Cautions
Discontinue immediately following shock or severe trauma; exogenous steroid should be administered in such circumstances
Adrenal insufficiency may develop requiring adrenal steroid replacement
Patients with liver disease in addition to metastatic lesion of adrenal cortex
Long-term administration of high doses may lead to brain damage
Mitotane plasma concentrations >20 mcg/mL associated with a greater incidence of high grade CNS toxicity
Increases hormone binding proteins, measurement of free cortisol and corticotropin (ACTH) levels may be useful in achieving optimal steroid replacement
Prolonged bleeding time reported; consider this possibility prior to any surgical intervention or if coadministered with anticoagulants
Reduces tumor mass but no evidence of cure
Advise women of reproductive potential of risks to fetus; use effective contraception
Ovarian macrocysts, often bilateral and multiple, reported in premenopausal patients; complications from cysts, including adnexal torsion and hemorrhagic cyst rupture, reported; in some cases, improvement after mitotane discontinuation reported; advise female patients to seek medical care if they experience gynecological symptoms such as vaginal bleeding and/or pelvic pain
Decreased blood androstenedione and decreased blood testosterone reported in females; increased sex hormone binding globulin in females and males, decreased blood free testosterone in males
Pregnancy & Lactation
Pregnancy Category: D
Lactation: Detected in breast milk; because of the potential for serious adverse reactions in nursing infants from mitotane, advise women to discontinue nursing during therapy and after treatment discontinuation for as long as mitotane plasma levels are detectable
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Adrenalytic agent; inhibits select adrenal cortex functions by binding to mitochondreal proteins resulting in adrenal atrophy and tumor death; atrophy observed in the zona fasciculata and reticularis
Absorption
5-40%
Distribution
Widely distributed with primary concentration in adipose tissue
Metabolism
Partly converted to an uncharacterized water-soluble metabolite
Elimination
Half-life: 18-159 days
Peak plasma time: 3-5 hr
Excretion
- 10% urine (PO); 25% urine (IV); excreted in urine as water-soluble metabolite
- Small amounts in bile
- Balance stored in tissues
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Patient Handout
Formulary
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