Mitotane

From Wikipedia, the free encyclopedia

Template:Short description Template:DMCA Template:Cs1 config Template:Short description Page Template:Infobox drug/styles.css has no content.

Page Module:Infobox/styles.css has no content.

Mitotane
Lua error in package.lua at line 80: module 'Module:InfoboxImage/data' not found.
Lua error in package.lua at line 80: module 'Module:InfoboxImage/data' not found.
Clinical data
Trade namesLysodren
Other names1,1-(Dichlorodiphenyl)-2,2-dichloroethane; o,p'-DDD
AHFS/Drugs.comMonograph
MedlinePlusa608050
License dataPage Template:Plainlist/styles.css has no content.
Routes of
administration		By mouth
ATC codePage Template:Plainlist/styles.css has no content.
Legal status
Legal statusPage Template:Plainlist/styles.css has no content.
Pharmacokinetic data
Bioavailability40%
Protein binding6%
Elimination half-life18–159 days
Identifiers
  • (RS)-1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)-ethyl]-benzene
CAS NumberPage Template:Plainlist/styles.css has no content.
PubChem CIDPage Template:Plainlist/styles.css has no content.
PubChem SIDPage Template:Plainlist/styles.css has no content.
IUPHAR/BPSPage Template:Plainlist/styles.css has no content.
DrugBankPage Template:Plainlist/styles.css has no content.
ChemSpiderPage Template:Plainlist/styles.css has no content.
UNIIPage Template:Plainlist/styles.css has no content.
KEGGPage Template:Plainlist/styles.css has no content.
ChEBIPage Template:Plainlist/styles.css has no content.
ChEMBLPage Template:Plainlist/styles.css has no content.
NIAID ChemDBPage Template:Plainlist/styles.css has no content.
PDB ligandPage Template:Plainlist/styles.css has no content.
CompTox Dashboard (EPA)Page Template:Plainlist/styles.css has no content.
Chemical and physical data
FormulaC14H10Cl4
Molar mass320.03 g·mol−1
3D model (JSmol)Page Template:Plainlist/styles.css has no content.
ChiralityRacemic mixture
Melting point76 to 78 °C (169 to 172 °F)
  • Clc1ccccc1C(c2ccc(Cl)cc2)C(Cl)Cl
  • 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 checkY
  • Key:JWBOIMRXGHLCPP-UHFFFAOYSA-N checkY
Data page
Template:Infobox drug/data page link
Page Template:Nobold/styles.css has no content.  (verify)

Mitotane, sold under the brand name Lysodren, is a steroidogenesis inhibitor and cytostatic antineoplastic medication which is used in the treatment of adrenocortical carcinoma and Cushing's syndrome.[3][4][5][6] It is a derivative of the early insecticide DDT and an isomer of p,p'-DDDTooltip dichlorodiphenyldichloroethane (4,4'-dichlorodiphenyldichloroethane) and is also known as 2,4'-(dichlorodiphenyl)-2,2-dichloroethane (o,p'-DDD).[7]

Medical uses

Mitotane has been produced by Bristol Myers Squibb but it is marketed as an orphan drug for adrenocortical carcinoma due to the small number of patients in need of it. Its main use is in those patients who have persistent disease despite surgical resection, those who are not surgical candidates, or those who have metastatic disease. In a 2007 retrospective study of 177 patients from 1985 to 2005 showed a significant increase in the recurrence-free interval after radical surgery followed by mitotane when compared to surgery alone.[8] The drug is also sometimes used in the treatment of Cushing's syndrome.[5]

Therapy with mitotane is initiated using an escalating regimen. The extent or intensity of the therapy is gradually increased. This depends on how well the individual patient tolerates the drug and the extent to which it affects the patient's performance status (according to the ECOG/Karnofsky Performance Status). Monitoring of the mitotane concentration in the blood is recommended. The general target value is ≥ 14 mg/L.[9]

Mitotane therapy is initiated using an escalating regimen. In all patients receiving mitotane therapy, glucocorticoid replacement is recommended, except for patients with persistent cortisol excess. In these cases, at least twice the standard replacement dose is generally required. This is due to the increased steroid excretion and the rise in cortisol-binding globulin. Mitotane-induced side effects must be monitored regularly and treated appropriately, avoiding over-, under-, or inappropriate treatment. Furthermore, initiating supportive therapy is advisable to improve mitotane tolerance. Ideally, this should be done before severe toxicity develops. Mitotane causes significant drug interactions due to strong induction of CYP3A4. Therefore, it is crucial to check all concomitant medications for CYP3A4 interactions and replace them with an alternative if necessary and available. Other healthcare providers should be advised not to initiate any other drug therapies without prior consultation.[9]

Side effects

The use of mitotane is unfortunately limited by side effects,[10] which, as reported by Schteingart et al., include anorexia and nausea (88%), diarrhea (38%), vomiting (23%), decreased memory and ability to concentrate (50%), rash (23%), gynecomastia (50%), arthralgia (19%), and leukopenia (7%).[11]

Pharmacology

Pharmacodynamics

Mitotane is an inhibitor of the adrenal cortex. It acts as an inhibitor of cholesterol side-chain cleavage enzyme (P450scc, CYP11A1), and also of 11β-hydroxylase (CYP11B1), 18-hydroxylase (aldosterone synthase, CYP11B2), and 3β-hydroxysteroid dehydrogenase (3β-HSD) to a lesser extent.[3][10] In addition, mitotane has direct and selective cytotoxic effects on the adrenal cortex, via an unknown mechanism, and thereby induces permanent adrenal atrophy similarly to DDD.[12][13] Mitotane has also been reported to interact with tubulin and inhibit its polymerization.[14]

Chemistry

Analogues of mitotane include aminoglutethimide, amphenone B, and metyrapone.

History

Mitotane was introduced in 1960 for the treatment of adrenocortical carcinoma.[5]

Society and culture

Generic names

Mitotane is the generic name of the medication and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, BANTooltip British Approved Name, and JANTooltip Japanese Accepted Name.[6][15]

Brand names

Mitotane is sold under the brand name Lysodren.[6]

Veterinary use

Mitotane is also used to treat Cushing's disease (pituitary-dependent Cushing's syndrome) in dogs. The medication is used in the controlled destruction of adrenal tissue, leading to a decrease in cortisol production.[16]

References

Page Template:Reflist/styles.css has no content.

  1. ^ Page Module:Citation/CS1/styles.css has no content."Product monograph brand safety updates". Health Canada. 7 July 2016. Retrieved 3 April 2024.
  2. ^ Page Module:Citation/CS1/styles.css has no content."Lysodren EPAR". European Medicines Agency. 12 June 2002. Retrieved 27 June 2024.
  3. ^ a b Page Module:Citation/CS1/styles.css has no content.Cavagnini F, Giraldi FP (18 May 2010). "Adrenal Causes of Hypercortisolism". In Jameson JL, De Groot LJ (eds.). Endocrinology - E-Book: Adult and Pediatric. Elsevier Health Sciences. pp. 1888–. ISBN 978-1-4557-1126-0.
  4. ^ Page Module:Citation/CS1/styles.css has no content.Hahner S, Fassnacht M (April 2005). "Mitotane for adrenocortical carcinoma treatment". Current Opinion in Investigational Drugs. 6 (4): 386–394. PMID 15898346.
  5. ^ a b c Page Module:Citation/CS1/styles.css has no content.Dang C, Trainer PJ (1 October 2010). "Medical Management of Cushing's Syndrome". In Bronstein MD (ed.). Cushing's Syndrome: Pathophysiology, Diagnosis and Treatment. Springer Science & Business Media. pp. 156–. ISBN 978-1-60327-449-4.
  6. ^ a b c Page Module:Citation/CS1/styles.css has no content.Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 382–. ISBN 978-1-4757-2085-3.
  7. ^ Page Module:Citation/CS1/styles.css has no content."Mitotane". PubChem. U.S. National Library of Medicine.
  8. ^ Page Module:Citation/CS1/styles.css has no content.Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, et al. (June 2007). "Adjuvant mitotane treatment for adrenocortical carcinoma". The New England Journal of Medicine. 356 (23): 2372–2380. doi:10.1056/NEJMoa063360. hdl:2318/37317. PMID 17554118.{{cite journal}}: CS1 maint: overridden setting (link)
  9. ^ a b Martin Fassnacht, Stylianos Tsagarakis, Massimo Terzolo, Antoine Tabarin, Anju Sahdev, John Newell-Price, Iris Pelsma, Ljiljana Marina, Kerstin Lorenz, Irina Bancos, Wiebke Arlt, Olaf M Dekkers: European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. In: European Journal of Endocrinology. Volume 189, Issue 1, July 2023, ISSN 0804-4643, Pages G1–G42, https://doi.org/10.1093/ejendo/lvad066 [retrieved July 6, 2024]
  10. ^ a b Page Module:Citation/CS1/styles.css has no content.Tzanela M, Vassiliadi DA, Tsagarakis S (24 March 2014). "Coincidental adrenal masses and adrenal cancer". In Harris PE, Bouloux PM (eds.). Endocrinology in Clinical Practice (Second ed.). CRC Press. pp. 216–. ISBN 978-1-84184-951-5.
  11. ^ Page Module:Citation/CS1/styles.css has no content.Schteingart DE, Motazedi A, Noonan RA, Thompson NW (September 1982). "Treatment of adrenal carcinomas". Archives of Surgery. 117 (9): 1142–1146. doi:10.1001/archsurg.1982.01380330010004. PMID 7115060.
  12. ^ Page Module:Citation/CS1/styles.css has no content.Sojka WS, Raizer J (28 September 2011). "Neurologic Complications of Hormonal Chemotherapies". In Lee EQ, Schiff D, Wen PY (eds.). Neurologic Complications of Cancer Therapy. Demos Medical Publishing. pp. 179–. ISBN 978-1-61705-019-0.
  13. ^ Page Module:Citation/CS1/styles.css has no content.Kannan CR (6 December 2012). "Cushing's Syndrome". The Adrenal Gland. Springer Science & Business Media. pp. 160–. ISBN 978-1-4613-1001-3.
  14. ^ Page Module:Citation/CS1/styles.css has no content.Baksheeva VE, La Rocca R, Allegro D, Derviaux C, Pasquier E, Roche P, et al. (2025). "NanoDSF Screening for Anti-tubulin Agents Uncovers New Structure–Activity Insights". Journal of Medicinal Chemistry. 68 (16): 17485–17498. doi:10.1021/acs.jmedchem.5c01008. PMC 12406199. PMID 40815226.
  15. ^ Page Module:Citation/CS1/styles.css has no content.Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 697–. ISBN 978-3-88763-075-1.
  16. ^ Page Module:Citation/CS1/styles.css has no content.Nichols R. "Canine Cushing's Syndrome: Diagnosis and Treatment Part 1: Typical, Atypical, and Pseudo-Cushing's Disease" (PDF). Archived from the original (PDF) on 21 October 2007.

Further reading

Page Template:Refbegin/styles.css has no content.

  • Page Module:Citation/CS1/styles.css has no content.Komissarenko VP, Chelnakova IS, Mikosha AS (1978). "Effect of o,p-dichlorodiphenyldichloroethane and perthane in vitro on glutathione reductase activity in the adrenals of dogs and guinea pigs". Bulletin of Experimental Biology and Medicine. 85 (2): 152–154. doi:10.1007/BF00800110. S2CID 23181221.

Lua error in package.lua at line 80: module 'Module:Navbox/configuration' not found. Lua error in package.lua at line 80: module 'Module:Navbox/configuration' not found. Lua error in mw.title.lua at line 404: bad argument #2 to 'title.new' (unrecognized namespace name 'Portal'). Lua error in package.lua at line 80: module 'Module:Authority control/config' not found.

Retrieved from "https://cosmopedia.co/index.php?title=Mitotane&oldid=1818411"