Chemical: Drug
mitotane

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PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

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The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for mitotane

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1045642 NC_000007.13:g.87138645A>G, NC_000007.14:g.87509329A>G, NG_011513.1:g.208920T>C, NM_000927.4:c.3435T>C, NP_000918.2:p.Ile1145=, rs10239679, rs11568726, rs117328163, rs17210003, rs2229108, rs386513066, rs60023214, rs9690664
A > G
SNP
I1145I
No VIP available CA VA
rs3745274 NC_000019.10:g.41006936G>T, NC_000019.9:g.41512841G>T, NG_007929.1:g.20638G>T, NM_000767.4:c.516G>T, NP_000758.1:p.Gln172His, XM_005258569.1:c.516G>T, XM_005258569.3:c.516G>T, XM_005258570.1:c.516G>T, XM_005258571.1:c.364+2490G>T, XM_006723050.2:c.516G>T, XM_011526546.1:c.516G>T, XM_011526547.1:c.516G>T, XM_011526548.1:c.484+2490G>T, XM_011526549.1:c.-75-1G>T, XM_011526550.1:c.364+2490G>T, XP_005258626.1:p.Gln172His, XP_005258627.1:p.Gln172His, XP_006723113.1:p.Gln172His, XP_011524848.1:p.Gln172His, XP_011524849.1:p.Gln172His, rs56308434, rs57685583
G > T
SNP
Q172H
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
Trade Names
  • Chloditan
  • Chlodithan
  • Chlodithane
  • Khlodithan
  • Lysodren
  • Mitotan
  • Mitotanum [INN-Latin]
Brand Mixture Names

PharmGKB Accession Id

PA164746157

Type(s):

Drug

Description

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.

Source: Drug Bank

Indication

For treatment of inoperable adrenocortical tumours; Cushing's syndrome

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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.

Source: Drug Bank

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.

Source: Drug Bank

Food Interaction

Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic and renal

Source: Drug Bank

Protein Binding

6%

Source: Drug Bank

Absorption

About 40% oral Lysodren is absorbed

Source: Drug Bank

Half-Life

18-159 days

Source: Drug Bank

Route of Elimination

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

Source: Drug Bank

Chemical Properties

Chemical Formula

C14H10Cl4

Source: Drug Bank

Isomeric SMILES

C1=CC=C(C(=C1)[C@H](C2=CC=C(C=C2)Cl)C(Cl)Cl)Cl

Source: Drug Bank

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

Source: Drug Bank

Canonical SMILES

ClC(Cl)C(C1=CC=C(Cl)C=C1)C1=CC=CC=C1Cl

Source: Drug Bank

Average Molecular Weight

320.041

Source: Drug Bank

Monoisotopic Molecular Weight

317.953661148

Source: Drug Bank

SMILES

ClC(Cl)C(C1=CC=C(Cl)C=C1)C1=CC=CC=C1Cl

Source: Drug Bank

InChI String

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

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
ABCB1
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
CYP2B6

Drug Targets

Gene Description
CYP11B1 (source: Drug Bank)
FDX1 (source: Drug Bank)
SERPINA6 (source: Drug Bank)
SHBG (source: Drug Bank)

Drug Interactions

Interaction Description
mitotane - acenocoumarol Mitotane may decrease the anticoagulant effect of acenocoumarol. (source: Drug Bank)
mitotane - anisindione Mitotane may decrease the anticoagulant effect of anisindione. (source: Drug Bank)
mitotane - dicumarol Mitotane may decrease the anticoagulant effect of dicumarol. (source: Drug Bank)
mitotane - spironolactone Spironolactone antagonizes the effect of mitotane (source: Drug Bank)
mitotane - warfarin Mitotane may decrease the anticoagulant effect of warfarin. (source: Drug Bank)

Curated Information ?

EvidenceDisease
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Adrenocortical Carcinoma

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to mitotane: 1

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Influence of the CYP2B6 polymorphism on the pharmacokinetics of mitotane. Pharmacogenetics and genomics. 2013. D'Avolio Antonio, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0015-3080-60
DrugBank:
DB00648
KEGG Drug:
D00420
PubChem Compound:
4211
PubChem Substance:
148675
46508319
Drugs Product Database (DPD):
463221
ChemSpider:
4066
Therapeutic Targets Database:
DAP000033
FDA Drug Label at DailyMed:
e9fba7d4-a0ec-4bfa-9b5b-ec97a9710fd3

Clinical Trials

These are trials that mention mitotane and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.