Bexarotene

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Bexarotene
Clinical data
Trade namesTargretin
AHFS/Drugs.comMonograph
MedlinePlusa608006
License data
Routes of
administration		By mouth, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding>99%
MetabolismHepatic (CYP3A4-mediated)
Elimination half-life7 hours
ExcretionParent drug and metabolites are eliminated primarily through the hepatobiliary system. Less than 1% is excreted in the urine unchanged.
Identifiers
  • 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)ethenyl]benzoic acid
JSmol)
  • O=C(O)c1ccc(cc1)C(/c2c(cc3c(c2)C(CCC3(C)C)(C)C)C)=C
  • InChI=1S/C24H28O2/c1-15-13-20-21(24(5,6)12-11-23(20,3)4)14-19(15)16(2)17-7-9-18(10-8-17)22(25)26/h7-10,13-14H,2,11-12H2,1,3-6H3,(H,25,26) checkY
  • Key:NAVMQTYZDKMPEU-UHFFFAOYSA-N checkY
  (verify)

Bexarotene, sold under the brand Targretin, is an

cutaneous T cell lymphoma (CTCL).[4] It is a third-generation retinoid.[5]

It was approved by the U.S.

generic medication.[6][7]

Medical uses

Bexarotene is

indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in people who are refractory to at least one prior systemic therapy (oral) and for the topical treatment of cutaneous lesions in patients with CTCL who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical).[3]

It has been used off-label for non-small cell lung cancer[8] and breast cancer.[9]

Contraindications

Known contraindications include:[10]

  • Hypersensitivity to the active substance or to any of the excipients in the preparation(s).
  • Pregnancy and lactation
  • Women of child-bearing potential without effective birth-control measures
  • History of pancreatitis
  • Uncontrolled
    hypercholesterolaemia
  • Uncontrolled
    hypertriglyceridaemia
  • Hypervitaminosis A
  • Uncontrolled thyroid disease
  • Hepatic insufficiency
  • Ongoing systemic infection

Adverse effects

Overall the most common adverse effects are skin reactions (mostly itchiness and rashes), leucopenia, headache, weakness, thyroid anomalies (which seem to be mediated by RXR-mediated downregulation of

thyroid stimulating hormone) and blood lipid anomalies such as hypercholesterolaemia (high blood cholesterol) and hyperlipidaemia, hypothyroidism.[3][10][11][12]

Interactions

Its plasma concentration may be increased by concomitant treatment with CYP3A4 inhibitors such as ketoconazole.[10] It may also induce CYP3A4, and hence CYP3A4 substrates like cyclophosphamide may have their plasma concentrations reduced.[10] Likewise consumption of grapefruit juice might increase bexarotene's plasma concentrations, hence potentially altering its therapeutic effects.[10]

Mechanism

Bexarotene is a retinoid that selectively activates retinoid X receptors (RXRs), as opposed to the retinoic acid receptors, the other major target of retinoic acid (the acid form of vitamin A).[12][13][14] By so doing it induces cell differentiation and apoptosis and prevents the development of drug resistance.[15] It also has anti-angiogenic effects and inhibits cancer metastasis.[15] The retinoic acid receptors (RARs) regulate cell differentiation and proliferation whereas RXRs regulate apoptosis.[11]

Physical properties

Bexarotene is a solid, white powder. It is poorly soluble in water; the solubility is estimated to be about 10-50 μM. It is soluble in DMSO at 65 mg/mL and in ethanol at 10 mg/mL with warming.[16]

History

Sanford-Burnham Medical Research Institute) collaborated on work that resulted in patent filings for the drug.[17]

The developer of bexarotene (brand name Targretin) was Ligand Pharmaceuticals, a San Diego biotech company which received FDA approval for the drug in 1999.[18] The FDA approved bexarotene on 29 December 1999.[19]

Japanese pharmaceutical Eisai bought the rights to Targretin and three other anti-cancer products from Ligand in 2006.[18] In the United States, patents on the drug expired in 2016.[18]

It received EMA approval on 29 March 2001.[20]

Early-stage preclinical studies suggested that bexarotene reduced

amyloid plaques and improved mental functioning in a small sample of mice engineered to exhibit Alzheimer's-like symptoms[21][22] although subsequent studies have yielded mixed results.[23][24][25][26][27]

The results of CCMR-One, a clinical trial of the effects of bexarotene on patients with multiple sclerosis operated by the University of Cambridge,[28] have shown that the drug can cause remyelination, but will not lead to the drug being used as a therapy, due to its risk profile.[29]

References

  1. FDA
    . Retrieved 22 October 2023.
  2. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 15 August 2023.
  3. ^ a b c "TARGRETIN (BEXAROTENE) CAPSULE [CARDINAL HEALTH]". DailyMed. Cardinal Health. March 2006. Retrieved 12 January 2014.
  4. S2CID 33092727
    .
  5. PMID 32473310
    .
  6. ^ "2022 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
  7. ^ "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. Retrieved 6 March 2023.
  8. S2CID 25374661
    .
  9. PMID 12637463
    .
  10. ^ a b c d e "Targretin Capsules - Summary of Product Characteristics". electronic Medicines Compendium. Eisai Ltd. 4 April 2013. Retrieved 14 January 2014.
  11. ^
    ISBN 978-0-07-162442-8
    .
  12. ^ a b "Targretin (bexarotene) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 31 January 2014.
  13. PMID 9147128
    .
  14. PMID 22020178
    .
  15. ^
    S2CID 31266907
    .
  16. ^ "Bexarotene MSDS". LC Labs. Archived from the original on 27 January 2013.
  17. ^ "Lymphoma Treatment: Targretin (bexarotene)". Timeline of Innovation. SRI International. Archived from the original on 19 November 2016. Retrieved 20 September 2013.
  18. ^ a b c Vinluan F (12 October 2011). "Generic cancer drug from Banner aims to take on Eisai's Targretin". MedCity News. Retrieved 11 February 2012.
  19. ^ "Bexarotene". Drugs.com. Archived from the original on 12 January 2014. Retrieved 12 January 2014.
  20. ^ "Targretin : EPAR - Product Information" (PDF). European Medicines Agency. Eisai Ltd. 3 April 2013. Retrieved 12 January 2014.
  21. PMID 22323736
    .
  22. ^ MedicalXpress (9 February 2012). "FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice". MedicalXpress. Retrieved 14 February 2012.
  23. PMID 23704552
    .
  24. PMID 23704553
    .
  25. PMID 23704554
    .
  26. S2CID 2999098
    .
  27. ^ "Anti-Cancer Drug Reverses Alzheimer's Disease In Mice". Medical News Today. 25 May 2013.
  28. ^ "Trials in Cambridge". Cambridge Neuroimmunology. Retrieved 25 September 2020.
  29. ^ "MS treatment a step closer after drug shown to repair nerve coating". the Guardian. 25 September 2020. Retrieved 25 September 2020.

External links

  • "Bexarotene". Drug Information Portal. U.S. National Library of Medicine.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Bexarotene&oldid=1194909423"