U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C14H10Cl4
Molecular Weight 320.041
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MITOTANE

SMILES

ClC(Cl)C(C1=CC=C(Cl)C=C1)C2=C(Cl)C=CC=C2

InChI

InChIKey=JWBOIMRXGHLCPP-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/cdi/mitotane.html

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. 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. Mitotane is used for treatment of inoperable adrenocortical tumours; Cushing's syndrome

Originator

Curator's Comment: # Bristol-Myers Squibb

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LYSODREN

Approved Use

LYSODREN is indicated in the treatment of inoperable adrenal cortical carcinoma of both functional and nonfunctional types.

Launch Date

1.05770877E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
11.3 mg/L
1 g 3 times / day multiple, oral
dose: 1 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MITOTANE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
14.3 mg/L
2 g 3 times / day multiple, oral
dose: 2 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MITOTANE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
543 mg × day/L
1 g 3 times / day multiple, oral
dose: 1 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MITOTANE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
790 mg × day/L
2 g 3 times / day multiple, oral
dose: 2 g
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MITOTANE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Doses

Doses

DosePopulationAdverse events​
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.264
unhealthy, 51.4+/-11.9
n = 12
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Age Group: 51.4+/-11.9
Sex: M+F
Population Size: 12
Sources: Page: p.264
Disc. AE: Anorexia, Nausea...
AEs leading to
discontinuation/dose reduction:
Anorexia (grade 1-2)
Nausea (grade 1-2)
Vomiting (grade 1-2)
Diarrhea (grade 1-2)
Abdominal pain (grade 1-2)
Sources: Page: p.264
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Sources: Page: p.1
Disc. AE: Central nervous system toxicity, Fetal damage...
AEs leading to
discontinuation/dose reduction:
Central nervous system toxicity
Fetal damage
Ovarian cyst
Adrenal insufficiency
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Abdominal pain grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.264
unhealthy, 51.4+/-11.9
n = 12
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Age Group: 51.4+/-11.9
Sex: M+F
Population Size: 12
Sources: Page: p.264
Anorexia grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.264
unhealthy, 51.4+/-11.9
n = 12
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Age Group: 51.4+/-11.9
Sex: M+F
Population Size: 12
Sources: Page: p.264
Diarrhea grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.264
unhealthy, 51.4+/-11.9
n = 12
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Age Group: 51.4+/-11.9
Sex: M+F
Population Size: 12
Sources: Page: p.264
Nausea grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.264
unhealthy, 51.4+/-11.9
n = 12
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Age Group: 51.4+/-11.9
Sex: M+F
Population Size: 12
Sources: Page: p.264
Vomiting grade 1-2
Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.264
unhealthy, 51.4+/-11.9
n = 12
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Age Group: 51.4+/-11.9
Sex: M+F
Population Size: 12
Sources: Page: p.264
Adrenal insufficiency Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Sources: Page: p.1
Central nervous system toxicity Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Sources: Page: p.1
Fetal damage Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Sources: Page: p.1
Ovarian cyst Disc. AE
2 g 3 times / day multiple, oral
Recommended
Dose: 2 g, 3 times / day
Route: oral
Route: multiple
Dose: 2 g, 3 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Adrenal cortical carcinoma
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
strong
likely (co-administration study)
Comment: LYSODREN’s CYP induction effect leads to an increase in dosage requirements for warfarin. Closely monitor patients for a change in anticoagulant dosage requirements when administering LYSODREN to patients receiving coumarin-type anticoagulants
Page: 4.0
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[The effects of o,p'-DDD on human adrenal steroid synthesis].
1984 Jul 20
Primary hypogonadism associated with o,p' DDD (mitotane) therapy.
1987
Mitotane enhances cytotoxicity of chemotherapy in cell lines expressing a multidrug resistance gene (mdr-1/P-glycoprotein) which is also expressed by adrenocortical carcinomas.
1991 Jul
Neuropsychologic and neurologic side effects of mitotane and reversibility of symptoms.
1992 Sep
Comparison of the adrenalytic activity of mitotane and a methylated homolog on normal adrenal cortex and adrenal cortical carcinoma.
1993
Expression of P-glycoprotein in relation to clinical manifestation, treatment and prognosis of adrenocortical cancer.
1993
Decreased cortisol secretion by adrenal glands perfused with the P-glycoprotein inhibitor valspodar and mitotane or doxorubicin.
2000 Apr
Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients: long-term survival in its adjuvant use.
2000 Oct
Acute hepatopathy associated with mitotane administration in a dog.
2006 Jul-Aug
Mitotane has an estrogenic effect on sex hormone-binding globulin and corticosteroid-binding globulin in humans.
2006 Jun
Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells.
2010 Feb 1
Preclinical investigation of nanoparticle albumin-bound paclitaxel as a potential treatment for adrenocortical cancer.
2012 Jan
FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.
2013 Sep 5
Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein.
2015 Feb
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Adrenal Cortical Carcinoma -Initial Dose: 2 to 6 g orally per day in 3 to 4 divided doses -Maintenance Dose: 9 to 10 g orally per day in 3 to 4 divided doses -Maximum Dose: May increase up to 16 g orally per day, if tolerated, in 3 to 4 divided doses; the highest doses used in studies were 18 to 19 g per day.
Route of Administration: Oral
Mitotane (10-40uM) inhibited basal and cAMP-induced cortisol secretion in human adrenocortical cancer NCI-H295 cells.
Name Type Language
MITOTANE
EMA EPAR   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
Mitotane [WHO-DD]
Common Name English
MITOTANE [EMA EPAR]
Common Name English
MITOTANE [USAN]
Common Name English
O,P'-DDD
Common Name English
MITOTANE [MI]
Common Name English
CHLODITAN
Brand Name English
MITOTANE [USP IMPURITY]
Common Name English
MITOTANE [ORANGE BOOK]
Common Name English
CB-313
Code English
O,P'-TDE
Common Name English
NSC-38721
Code English
mitotane [INN]
Common Name English
CB 313
Code English
MITOTANE [MART.]
Common Name English
O,P'-DDD,O P'-TDE
Common Name English
MITOTANE [HSDB]
Common Name English
MITOTAN
Common Name English
CHLODITHANE
Brand Name English
OPEPRIM
Brand Name English
MITOTANE [JAN]
Common Name English
MITOTANE [USP-RS]
Common Name English
BENZENE, 1-CHLORO-2-(2,2-DICHLORO-1-(4-CHLOROPHENYL)ETHYL)-, (±)-
Systematic Name English
(±)-1,1-DICHLORO-2-(O-CHLOROPHENYL)-2-(P-CHLOROPHENYL)ETHANE
Common Name English
LYSODREN
Brand Name English
MITOTANE [USP MONOGRAPH]
Common Name English
BENZENE, 1-CHLORO-2-(2,2-DICHLORO-1-(4-CHLOROPHENYL)ETHYL)-
Systematic Name English
MITOTANE [VANDF]
Common Name English
Classification Tree Code System Code
WHO-ATC L01XX23
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
EMA ASSESSMENT REPORTS LYSODREN (AUTHORIZED: ADRENAL CORTEX NEOPLASMS)
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
LIVERTOX NBK548445
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
NCI_THESAURUS C2355
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
EU-Orphan Drug EU/3/02/102
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
WHO-VATC QL01XX23
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
Code System Code Type Description
DRUG CENTRAL
1820
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
IUPHAR
6957
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
EVMPD
SUB09010MIG
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
MESH
D008939
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
CAS
53-19-0
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
NCI_THESAURUS
C664
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
EPA CompTox
DTXSID9020372
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
DAILYMED
78E4J5IB5J
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
PUBCHEM
4211
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
SMS_ID
100000085449
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-166-6
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
MERCK INDEX
m7571
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY Merck Index
RS_ITEM_NUM
1445007
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
DRUG BANK
DB00648
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
INN
2597
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
ChEMBL
CHEMBL1670
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
WIKIPEDIA
MITOTANE
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
RXCUI
7004
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY RxNorm
FDA UNII
78E4J5IB5J
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
HSDB
3240
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
NSC
38721
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY
NDF-RT
N0000185506
Created by admin on Sat Dec 16 05:00:54 UTC 2023 , Edited by admin on Sat Dec 16 05:00:54 UTC 2023
PRIMARY Cytochrome P450 3A4 Inducers [MoA]