II. Indications

  1. Adrenocortical adenocarcinoma (non-operable, palliative management)

III. Contraindications

  1. Acute shock states or Trauma

IV. Mechanism

  1. Synthetic derivative of the banned Pesticide DDT (dichlorodiphenyl trichloroethane)
  2. Mitotane deposits in fatty tissue and is slowly released
  3. Mitotane is toxic to cells of the Adrenal Cortex, resulting in anti-adrenocorticoid activity
    1. Metabolized in the Adrenal Cortex to a reactive acyl chloride intermediate
    2. Metabolites bind adrenal Proteins, and inhibits adrenal cortical Hormone synthesis

V. Medications

  1. Mitotane oral tablets (scored): 500 mg

VI. Dosing

  1. See other references for disease specific dosing protocols

VII. Adverse Effects

  1. Does not suppress the Bone Marrow
  2. Adrenal Insufficiency
  3. Bleeding Diathesis
  4. Gastrointestinal distress
  5. Central Nervous System toxicity
    1. Cognitive Impairment
    2. Major Depression
  6. Constitutional symptoms
    1. Lethargy
    2. Weakness
    3. Dizziness

VIII. Safety

  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters)
    1. Use reliable Contraception
  3. Monitoring
    1. Neurologic and psychiatric periodic testing (prolonged use >2 years)

IX. Drug Interactions

  1. Mitotane decreases the effect of other agents
    1. Warfarin
    2. Corticosteroids

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Ontology: Mitotane (C0026256)

Definition (NCI_NCI-GLOSS) An anticancer drug used in treating adrenocortical cancer and ACTH-producing pituitary tumors (Cushing's disease).
Definition (NCI) A synthetic derivative of the insecticide dichlorodiphenyl trichloroethane (DDT) with anti-adrenocorticoid properties. Following its metabolism in the adrenal cortex to a reactive acyl chloride intermediate, mitotane covalently binds to adrenal proteins, specifically inhibiting adrenal cortical hormone production. (NCI04)
Definition (MSH) A derivative of the insecticide DICHLORODIPHENYLDICHLOROETHANE that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression.
Definition (PDQ) A synthetic derivative of the insecticide dichlorodiphenyl trichloroethane (DDT) with anti-adrenocorticoid properties. Following its metabolism in the adrenal cortex to a reactive acyl chloride intermediate, mitotane covalently binds to adrenal proteins, specifically inhibiting adrenal cortical hormone production. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39506&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39506&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C664" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D008939
SnomedCT 255662000, 26288002, 404865004
LNC LP18384-5, MTHU004186
English Mytotan, o,p-DDD, ortho,para-DDD, Benzene, 1-chloro-2-(2,2-dichloro-1-(4-chlorophenyl)ethyl)-, ortho,para DDD, 2,2-Bis(2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane, 2,4'-Dichlorodiphenyldichloroethane, 2-(2-Chlorophenyl)-2-(4-chlorophenyl)-1,1-dichloroethane, 1,1-Dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, 1-Chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene, mitotane, Ortho,para-DDD, DDD O P, ORTHO PARA DDD, mitotane (medication), o,P'-DDD, o,P'-DDD (medication), Mitotane [Chemical/Ingredient], 1, 1-Dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, 2, 4'-Dichlorodiphenyldichloroethane, Ethane, 2-(o-chlorophenyl)-2-(p-chlorophenyl)-1,1-dichloro-, (o,p)-DDD, 2, 2-Bis(2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane, O,p'-DDD, o,p'-DDD, op'DDD - Mitotane, 1,1-Dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane, Mitotane (substance), Mitotane (product), DDD, o,p' - DDD, Mitotane, MITOTANE
Swedish Mitotan
Czech mitotan
Finnish Mitotaani
Russian ORTO, PARA-DIKHLORDIFENILDIKHLORETAN, KHLODITAN, MITOTAN, O,P-DDD, МИТОТАН, ОРТО, ПАРА-ДИХЛОРДИФЕНИЛДИХЛОРЭТАН, ХЛОДИТАН
Japanese ミトーテン, クロジタン, マイトテイン, ミトタン, オルトパラDDD
German ORTHO PARA DDD, DDD O P, Mitotan, o,p-DDD, ortho,para-DDD
Polish O,p-dwuchlorodwufenylodwuchloroetan, Mitotan
Spanish 1,1-dicloro-2- (o-clorofenil-2- (p-clorofenil) etano, o,p'-DDD, O,p'-DDD, mitotano (sustancia), mitotano, mitotano (producto), Mitotano, o,p-DDD, orto para-DDD
French Mitotane
Italian Mitotano
Portuguese Mitotano, o,p-DDD, orto para-DDD