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2D Structure
Also known as: 53-19-0, Mitotan, Lysodren, O,p'-ddd, Chlodithane, Chloditan
Molecular Formula
C14H10Cl4
Molecular Weight
320.0  g/mol
InChI Key
JWBOIMRXGHLCPP-UHFFFAOYSA-N
FDA UNII
78E4J5IB5J

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.
The mechanism of action of mitotane is as a Cytochrome P450 3A4 Inducer.
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene
2.1.2 InChI
InChI=1S/C14H10Cl4/c15-10-7-5-9(6-8-10)13(14(17)18)11-3-1-2-4-12(11)16/h1-8,13-14H
2.1.3 InChI Key
JWBOIMRXGHLCPP-UHFFFAOYSA-N
2.1.4 Canonical SMILES
C1=CC=C(C(=C1)C(C2=CC=C(C=C2)Cl)C(Cl)Cl)Cl
2.2 Other Identifiers
2.2.1 UNII
78E4J5IB5J
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Chloditan

2. Chlodithane

3. Khloditan

4. Lysodren

5. Mytotan

6. O,p-ddd

7. Ortho,para Ddd

8. Ortho,para-ddd

2.3.2 Depositor-Supplied Synonyms

1. 53-19-0

2. Mitotan

3. Lysodren

4. O,p'-ddd

5. Chlodithane

6. Chloditan

7. Khlodithan

8. Chlodithan

9. 2,4'-ddd

10. 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane

11. O,p'-tde

12. 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene

13. Mitotano

14. Opeprim

15. Nci-c04933

16. 2,4'-dichlorodiphenyldichloroethane

17. 1-chloro-2-(2,2-dichloro-1-(4-chlorophenyl)ethyl)benzene

18. O,p'-dichlorodiphenyldichloroethane

19. Cb 313

20. 2,4'-dichlorophenyldichlorethane

21. Benzene, 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]-

22. Cb-313

23. Nsc 38721

24. Nsc-38721

25. 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane

26. 2-(2-chlorophenyl)-2-(4-chlorophenyl)-1,1-dichloroethane

27. 2-(o-chlorophenyl)-2-(p-chlorophenyl)-1,1-dichloroethane

28. 1,1-dichloro-2,2-bis(2,4'-dichlorophenyl)ethane

29. O,p'-ddd,o P'-tde

30. Nsc38721

31. 1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane

32. 2,2-bis(2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane

33. Benzene, 1-chloro-2-(2,2-dichloro-1-(4-chlorophenyl)ethyl)-

34. 78e4j5ib5j

35. 2,4'-ddd;o,p'-ddd

36. Ethane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-

37. Ethane, 2-(o-chlorophenyl)-2-(p-chlorophenyl)-1,1-dichloro-

38. 2,4 Inverted Exclamation Marka-ddd

39. Mitotanum [inn-latin]

40. O,p-tde

41. Ncgc00015226-07

42. 1-chloro-4-[2,2-dichloro-1-(2-chlorophenyl)ethyl]benzene

43. 2,4'-ddd 10 Microg/ml In Cyclohexane

44. Mitotanum

45. 2,4'-ddd 100 Microg/ml In Cyclohexane

46. Dsstox_cid_372

47. Mitotano [inn-spanish]

48. Dsstox_rid_75548

49. Dsstox_gsid_20372

50. 2,4'-(2,2-dichloroethane-1,1-diyl)bis(chlorobenzene)

51. Cb313

52. Ddd, O,p'-

53. Cas-53-19-0

54. Lysodren (tn)

55. Smr000326696

56. Ccris 4397

57. Hsdb 3240

58. Sr-01000075751

59. Einecs 200-166-6

60. (o,p)-ddd

61. (2,4'-dichlorodiphenyl)dichloroethane

62. Mitotane (jan/usp/inn)

63. Brn 2056007

64. Unii-78e4j5ib5j

65. Ai3-07575

66. Prestwick_75

67. Ethane,1-dichloro-

68. Mfcd00000850

69. Mitotane (lysodren)

70. Mitotane [usan:usp:inn:ban:jan]

71. Spectrum_001959

72. Mitotane [hsdb]

73. Mitotane [usan]

74. Ddd-o,p'

75. Mitotane [inn]

76. Mitotane [jan]

77. Mitotane [mi]

78. Mitotane [vandf]

79. (+-)-1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane

80. Spectrum2_000916

81. Spectrum3_000869

82. Spectrum4_000709

83. Spectrum5_002060

84. Mitotan-[ring-13c6]

85. Mitotane [mart.]

86. Mitotane [usp-rs]

87. Mitotane [who-dd]

88. C 3010

89. (o,p')-ddd

90. Schembl4040

91. Chembl1670

92. Mitotane [ema Epar]

93. Lopac0_000251

94. Wln: Gygyr Bg&r Dg

95. Bspbio_002517

96. Kbiogr_001237

97. Kbioss_002513

98. Spectrum330082

99. Mls001335899

100. Mls001335900

101. Mls002152914

102. Mls002153233

103. Divk1c_000703

104. Spbio_000792

105. Mitotane [orange Book]

106. Chebi:6954

107. Gtpl6957

108. Mitotane [usp Impurity]

109. Mitotane, >=98% (hplc)

110. Dtxsid9020372

111. Mitotane [usp Monograph]

112. 2,4'-ddd, Analytical Standard

113. Hms502d05

114. Kbio1_000703

115. Kbio2_002505

116. Kbio2_005073

117. Kbio2_007641

118. Kbio3_002017

119. Ninds_000703

120. Hms1923k19

121. Hms2091e07

122. Hms2232c16

123. Hms3260d04

124. Hms3369h10

125. Hms3655g06

126. Hms3715h07

127. Hms3869f13

128. Pharmakon1600-00330082

129. Bcp11663

130. Tox21_110103

131. Tox21_302804

132. Tox21_500251

133. Ccg-40014

134. Nsc755849

135. S1732

136. 1,2-bis(2,4'-dichlorophenyl)ethane

137. Akos006028802

138. Benzene, 1-chloro-2-(2,2-dichloro-1-(4-chlorophenyl)ethyl)-, (+-)-

139. Tox21_110103_1

140. Cs-1500

141. Db00648

142. Lp00251

143. Nsc-755849

144. Sdccgsbi-0050239.p006

145. Idi1_000703

146. 2,4'-ddd 100 Microg/ml In Methanol

147. Ncgc00015226-02

148. Ncgc00015226-03

149. Ncgc00015226-04

150. Ncgc00015226-05

151. Ncgc00015226-06

152. Ncgc00015226-08

153. Ncgc00015226-09

154. Ncgc00015226-10

155. Ncgc00015226-11

156. Ncgc00015226-12

157. Ncgc00091374-01

158. Ncgc00091374-02

159. Ncgc00091374-03

160. Ncgc00091374-04

161. Ncgc00091374-05

162. Ncgc00091374-06

163. Ncgc00256452-01

164. Ncgc00260936-01

165. As-11690

166. Hy-13690

167. Nci60_003688

168. 2,4'-ddd 1000 Microg/ml In N-hexane

169. Sbi-0050239.p004

170. Eu-0100251

171. Ft-0605518

172. M3304

173. Sw199619-3

174. En300-37268

175. 2,4 Inverted Exclamation Marka-ddd;o,p'-ddd

176. 2,4'-ddd, Pestanal(r), Analytical Standard

177. C75491

178. D00420

179. Ab00052337-09

180. Ab00052337_10

181. 000m850

182. Q417465

183. Sr-01000075751-1

184. Sr-01000075751-3

185. Sr-01000075751-6

186. Z425389592

187. 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane

188. Ethane,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-

189. 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene #

190. Mitotane, United States Pharmacopeia (usp) Reference Standard

191. (+/-)-1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane

192. 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane, Analytical Standard

193. Benzene, 1-chloro-2-(2,2-dichloro-1-(4-chlorophenyl)ethyl)-, (+/-)-

194. 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane For Diagnostic Uses (cancer Investigation), >=98% (hplc)

195. 1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane, For Diagnostic Uses (cancer Investigation), >=98% (hplc)

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 320.0 g/mol
Molecular Formula C14H10Cl4
XLogP36.2
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count0
Rotatable Bond Count3
Exact Mass319.950711 g/mol
Monoisotopic Mass317.953661 g/mol
Topological Polar Surface Area0 Ų
Heavy Atom Count18
Formal Charge0
Complexity248
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count1
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Information
1 of 2  
Drug NameLysodren
PubMed HealthMitotane (By mouth)
Drug ClassesAdrenocortical Suppressant, Steroid Synthesis Inhibitor
Drug LabelLYSODREN (mitotane tablets, USP) is an oral chemotherapeutic agent. It is best known by its trivial name, o,p-DDD, and is chemically, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane. The chemical structure is shown below:LYSODREN is a...
Active IngredientMitotane
Dosage FormTablet
RouteOral
Strength500mg
Market StatusPrescription
CompanyBristol Myers Squibb

2 of 2  
Drug NameLysodren
PubMed HealthMitotane (By mouth)
Drug ClassesAdrenocortical Suppressant, Steroid Synthesis Inhibitor
Drug LabelLYSODREN (mitotane tablets, USP) is an oral chemotherapeutic agent. It is best known by its trivial name, o,p-DDD, and is chemically, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl) ethane. The chemical structure is shown below:LYSODREN is a...
Active IngredientMitotane
Dosage FormTablet
RouteOral
Strength500mg
Market StatusPrescription
CompanyBristol Myers Squibb

4.2 Therapeutic Uses

Antineoplastic Agents, Hormonal

National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)


Mitotane is indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. /Included in US product label/

US Natl Inst Health; DailyMed. Current Medication Information for LYSODREN (mitotane) tablets (March 2009). Available from, as of June 22, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=9478


Mitotane is also used in the treatment of Cushing's syndrome. /Not included in US or Canadian product labeling/

USP Convention. USPDI-Drug Information for the Health Care Professional. 14th ed. Volume I. Rockville, MD: United States Pharmacopeial Convention, Inc., 1994. (Plus Updates)., p. 1937


The effect of mitotane therapy in treatment of adrenocortical carcinoma was studied in 88 patients (mean age 46 yr); 80 of these patients underwent surgery and 59 also received oral mitotane capsule, at a mean initial dose of 10 g/day and a mean maintenance dose of 7 g/day for a mean duration of 10.5 months. The median disease free interval after surgery was 12.1 months. Tumor dissemination occurred in 82% of the patients, most commonly to the lung, liver and adjacent organs. The median survival time was 14.5 months, and the 5 yr survival was 22%. Age over 40 yr and the presence of metastases at the time of diagnosis were the only factors recognized as indicating a poor prognosis. Mitotane controlled hormonal secretion in 75% of the patients. Eight mitotane treated patients had partial tumor regression, but the drug did not have a significant effect on survival. It was concluded that adrenocortical carcinoma carries a poor prognosis; mitotane therapy may offer transient benefits, particularly in controlling endocrine symptoms.

Luton JP et al; N Eng J Med 322 (26): 1195-1201 (1990)


4.3 Drug Warning

/BOXED WARNING/ WARNINGS: Lysodren (mitotane tablets, USP) should be administered under the supervision of a qualified physician experienced in the uses of cancer chemotherapeutic agents. Lysodren should be temporarily discontinued immediately following shock or severe trauma since adrenal suppression is its prime action. Exogenous steroids should be administered in such circumstances, since the depressed adrenal may not immediately start to secrete steroids.

US Natl Inst Health; DailyMed. Current Medication Information for LYSODREN (mitotane) tablets (Updated: November 2013). Available from, as of April 24, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e9fba7d4-a0ec-4bfa-9b5b-ec97a9710fd3


... Seventeen consecutive patients who were treated with mitotane after radical resection of adrenocortical cancer (ACC) from 1999 to 2005 underwent physical examination, routine laboratory evaluation, monitoring of mitotane concentrations, and a hormonal work-up at baseline and every 3 months till ACC relapse or study end (December 2007). Mitotane toxicity was graded using NCI CTCAE criteria. All biochemical measurements were performed at our center and plasma mitotane was measured by an in-house HPLC assay. All the patients reached mitotane concentrations >14 mg/L and none of them discontinued definitively mitotane for toxicity; 14 patients maintained consistently elevated mitotane concentrations despite tapering of the drug. Side effects occurred in all patients but were manageable with palliative treatment and adjustment of hormone replacement therapy. Mitotane affected adrenal steroidogenesis with a more remarkable inhibition of cortisol and DHEAS than aldosterone. Mitotane induced either perturbation of thyroid function mimicking central hypothyroidism or, in male patients, inhibition of testosterone secretion. The discrepancy between salivary and serum cortisol, as well as between total and free testosterone, is due to the mitotane-induced increase in hormone-binding proteins which complicates interpretation of hormone measurements. ...

PMID:18824557 Daffara F et al; Endocr Relat Cancer 15 (4): 1043-53 (2008).


/Investigators/ prospectively studied 7 patients with adrenocortical cancer on mitotane therapy. Before and 1 and 2 or more weeks after starting mitotane we determined the platelet counts, bleeding times and global coagulation parameters. All patients had a normal bleeding time before treatment. In 6 cases the bleeding time became prolonged (245-555 s). Four patients exhibited platelet aggregation responses compatible with an aspirin-like defect. It is concluded that mitotane may cause a clinically relevant defect of platelet function.

PMID:1828976 Haak HR et al; Eur J Cancer 27 (5): 638-41(1991).


Gastrointestinal disturbances (anorexia, nausea, vomiting, and diarrhea) occur in 80% of patients and are usually dose limiting. About 40% of patients experience central nervous system side effects (lethargy and somnolence, 25%; dizziness or vertigo, 15%). About 15% of patients develop dermatitis.

American Medical Association, Council on Drugs. AMA Drug Evaluations Annual 1994. Chicago, IL: American Medical Association, 1994., p. 2081


For more Drug Warnings (Complete) data for MITOTANE (28 total), please visit the HSDB record page.


4.4 Drug Indication

For treatment of inoperable adrenocortical tumours; Cushing's syndrome


Symptomatic treatment of advanced (unresectable, metastatic or relapsed) adrenal cortical carcinoma. The effect of Lysodren on non-functional adrenal cortical carcinoma is not established.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Mitotane is an oral chemotherapeutic agent indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types. Mitotane can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. The administration of Mitotane alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-B-hydroxyl cortisol.


5.2 MeSH Pharmacological Classification

Antineoplastic Agents, Hormonal

Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079) (See all compounds classified as Antineoplastic Agents, Hormonal.)


5.3 FDA Pharmacological Classification
5.3.1 Active Moiety
MITOTANE
5.3.2 FDA UNII
78E4J5IB5J
5.3.3 Pharmacological Classes
Cytochrome P450 3A4 Inducers [MoA]
5.4 ATC Code

L01XX23


L - Antineoplastic and immunomodulating agents

L01 - Antineoplastic agents

L01X - Other antineoplastic agents

L01XX - Other antineoplastic agents

L01XX23 - Mitotane


5.5 Absorption, Distribution and Excretion

Absorption

About 40% oral Lysodren is absorbed


Route of Elimination

A variable amount of metabolite (1%-17%) is excreted in the bile and the balance is apparently stored in the tissues.


Clinical studies indicate that approximately 40% of mitotane is absorbed after oral administration. After daily doses of 5 to 15 g, concentrations of 10 to 90 ug/mL of unchanged drug and 30 to 50 ug/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.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 1253


Peak plasma mitotane concentrations occur 3-5 hours after a single oral dose of the drug and distribution of the drug between plasma and tissues is complete within 12 hours. In one study in patients with adrenocortical carcinoma who were receiving an oral dosage of 5-15 g of mitotane daily, serum mitotane concentrations were 7-90 ug/mL and serum concentrations of mitotane metabolites were 29-54 ug/mL. Serum concentrations of mitotane and its metabolites appear to plateau after about 8 weeks of continuous mitotane therapy and generally have not appeared to correlate with therapeutic or toxic effects of the drug; however, some data suggest that tumor regression in patients with adrenocortical carcinoma is associated with serum mitotane concentrations greater than 14 ug/mL and that adverse CNS effects are associated with serum concentrations greater than 20 ug/mL.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1178


Mitotane and its metabolites are distributed to essentially all body tissues with fat being the primary storage site; there is no selective accumulation in the adrenals. Following discontinuance of mitotane therapy, persistent plasma concentrations of mitotane and its metabolites are probably caused by their slow release from fat and other tissues. Although unchanged mitotane has not been detected in CSF, small amounts of one mitotane metabolite have been detected in CSF.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1178


It is not known if mitotane or its metabolites cross the placenta or distribute into milk.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1178


For more Absorption, Distribution and Excretion (Complete) data for MITOTANE (11 total), please visit the HSDB record page.


5.6 Metabolism/Metabolites

Hepatic and renal


In rabbits and in humans, ortho,para'-dichlorodiphenylacetic acid has been identified as major urinary metabolite.../of mitotane/.

The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 324


With oral dosing of mitotane, metabolites o,p'-dichlorodiphenylacetic acid and its mono- and dihydroxylated derivatives appeared in urine as well as in stools. An unsaturated metabolite, o,p'-DDE was observed in plasma & tissues of man.

TOUITOU Y ET AL; ANN ENDOCRINOL (PARIS) 38 13 (1977)


Urine samples were obtained from four patients with Cushing syndrome who had been treated with o,p'-DDD. Methyl-thio containing metabolites and other metabolites of o,p'-DDD were detected in the urine samples by gas chromatographic mass spectrometry. These methyl-thio containing metabolites showed smaller peaks in the gas chromatogram than other peaks derived from other metabolites of o,p'-DDD. Although the biological significance of the pathway forming these methyl-thio containing metabolites is not known at the present /time/. ...

PMID:2724646 Inouye M et al; Jpn J Med 28 (1): 41-4 (1989)


Mitotane is metabolized in the liver and other tissues principally to o,p'-dichlorodiphenyl-ethene and -acetate derivatives; small amounts of these derivatives apparently undergo aromatic hydroxylation and glycine conjugation.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1178


For more Metabolism/Metabolites (Complete) data for MITOTANE (6 total), please visit the HSDB record page.


5.7 Biological Half-Life

18-159 days


Mitotane reportedly has a plasma elimination half-life of 18-159 days.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1178


5.8 Mechanism of Action

Its biochemical mechanism of action is unknown, although data are available to suggest that the drug modifies the peripheral metabolism of steroids as well as directly suppressing the adrenal cortex.


The exact mechanisms of action of mitotane have not been clearly established. Although mitotane is an adrenocortical cytotoxic agent, the drug can also apparently inhibit adrenocortical function without causing cellular destruction. Mitotane appears to selectively inhibit adrenocortical function as well as functional and nonfunctional adrenocortical neoplasms by a direct cytotoxic effect; this effect may be mediated through covalent bonding of mitotane metabolites to mitochondrial proteins. The drug causes focal degeneration in the zona fasciculata and reticularis of the adrenal cortex with resultant atrophy. The drug usually causes only minimal degeneration in the zona glomerulosa (site of aldosterone biosynthesis); however, the zona glomerulosa may be damaged with prolonged mitotane therapy. Mitotane also reportedly inhibits the growth of human renal carcinoma cells, astrocytoma cells, and fibroblasts in vitro.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1178


Mitotane inhibits production of corticosteroids and alters extra-adrenal metabolism of endogenous and exogenous steroids. Mitotane inhibits the normal 11-beta-hydroxylation of 11-deoxycortisol (compound S) and 11-deoxycorticosterone (DOC) in the adrenal cortex, thus blocking conversion of compound S to cortisol (hydrocortisone) and DOC to corticosterone. The drug can also inhibit 18-hydroxylase activity in the adrenal cortex and thus decrease the production of aldosterone by blocking the conversion of corticosterone to 18-hydroxycorticosterone (the immediate precursor of aldosterone). Mitotane decreases cortisol secretion rate; plasma cortisol concentration; urinary excretion of free cortisol, 17-hydroxycorticosteroids (17-OHCS), 17-ketosteroids (17-KS), and 17-ketogenic steroids; and adrenocortical response to stimulation by corticotropin (ACTH). A feedback increase in plasma corticotropin concentration is generally observed in patients receiving mitotane; however, a lack of feedback increase or a decrease in plasma corticotropin concentration has been observed in some patients. Therefore, it has been suggested that the drug may have a partial suppressive effect on pituitary corticotropin-secreting cells. Mitotane apparently increases the extra-adrenal metabolism of cortisol to 6-beta-hydroxycortisol which results in decreased urinary excretion of measurable 17-OHCS; this occurs even in the presence of unchanged cortisol secretion rate or plasma cortisol concentration. Although urinary excretion of aldosterone metabolites may decrease, serum aldosterone concentrations may remain in the normal range. Therefore, it has been suggested that mitotane may also alter the extra-adrenal metabolism of aldosterone. Mitotane decreases the extra-adrenal conversion of androgens to androsterone and etiocholanolone; this results in decreased urinary excretion of 17-KS. The drug also inhibits the extra-adrenal conversion of 3-beta-hydroxysteroids to 3-alpha-hydroxypregnane derivatives.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1178


Mitotane has uricosuric activity and thus decreases serum uric acid concentrations; the exact mechanism of the increase in renal uric acid clearance has not been established.

American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1178


Mitotane can best be described as an adrenal cytotoxic agent, although it can cause adrenal inhibition, apparently without cellular destruction. Its biochemical mechanism of action is unknown. Data are available to suggest that the drug modifies the peripheral metabolism of steroids as well as directly suppressing the adrenal cortex. The administration of mitotane alters the extra-adrenal metabolism of cortisol in man; leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. The drug apparently causes increased formation of 6-beta-hydroxycortisol.

US Natl Inst Health; DailyMed. Current Medication Information for LYSODREN (mitotane) tablets (March 2009). Available from, as of June 22, 2009: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=9478


For more Mechanism of Action (Complete) data for MITOTANE (7 total), please visit the HSDB record page.