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Tretinoin

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Tretinoin
Clinical data
Trade namesAvita, Renova, Retin-a
AHFS/Drugs.comMonograph
MedlinePlusa682437
License data
Pregnancy
category
  • AU: X (High risk)
Routes of
administration		Topical, oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: WARNING[1]Rx-only
Pharmacokinetic data
Protein binding> 95%
Elimination half-life0.5-2 hours
Identifiers
  • (2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.005.573 Edit this at Wikidata
Chemical and physical data
FormulaC20H28O2
Molar mass300.4412 g/mol g·mol−1
3D model (JSmol)
Melting point180 °C (356 °F)
  • O=C(O)\C=C(\C=C\C=C(\C=C\C1=C(\CCCC1(C)C)C)C)C
  • InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14+ checkY
  • Key:SHGAZHPCJJPHSC-YCNIQYBTSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Tretinoin (etymology and pronunciation) is retinoic acid in pharmaceutical form. One of several retinoids, it is the carboxylic acid form of vitamin A and is also known as all-trans retinoic acid or ATRA. It is a first generation topical retinoid commonly used to treat acne vulgaris and keratosis pilaris. It is available as a cream or gel (brand names Aberela, Airol, A-Ret, Atralin, Avita, Retacnyl, Refissa, Renova, Retin-A, Retino-A, ReTrieve, or Stieva-A). The most common strengths are 0.025%, 0.05% and 0.1%. It is also used to treat acute promyelocytic leukemia (APL), and is sold for this indication by Roche under the brand name Vesanoid. It is also available as a generic. Its isomer, isotretinoin, is also an acne drug.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.[2]

Medical uses

Dermatology

Tretinoin was co-developed by James Fulton and Albert Kligman in 1969.[3] Together, Fulton and Kligman are credited as the inventors of Retin-A.[3] Fulton was a researcher at the University of Pennsylvania at the time.[3] The University of Pennsylvania held the patent for Retin-A, which it licensed to pharmaceutical companies.[3]

Tretinoin is most commonly used as a form of acne treatment.[4] It was the first retinoid developed for this type of topical use.[citation needed] Tretinoin is the best studied retinoid in the treatment of photoaging.[5] It is used by some as a hair loss treatment [6] and is a component of many commercial products that are advertised as being able to slow skin aging or remove wrinkles.[7][8] Topical tretinoin is also used to treat and reduce the appearance of stretch marks by increasing collagen production in the dermis.[9]

Leukemia

Tretinoin, marketed as Vesanoid, is used to treat at least one form of cancer (acute promyelocytic leukemia, also called acute myeloid leukemia subtype M3), usually together with other drugs, by causing the immature promyelocytes to differentiate (i.e. mature).[10][11]

The pathology of the leukemia is due to the highly proliferative immature cells; retinoic acid drives these cells to develop into functional cells, which helps to alleviate the disease.[citation needed] It is usually prescribed for 15 days every three months at about 8–10 10-mg capsules per day.[citation needed]

Clinical pharmacology

Successfully treating acute promyelocytic leukemia (APL) with Tretinoin was a major breakthrough in APL therapy.[12] It works in APL because the majority of cases involve a chromosomal translocation of chromosomes 15 and 17, which causes genetic fusion of the retinoic acid receptor (RAR) gene to the promyelocytic leukemia (PML) gene.[13] This fusion PML-RAR protein is responsible for preventing immature myeloid cells from differentiating into more mature cells. This block in differentiation is thought to cause leukemia. ATRA acts on PML-RAR to lift this block, causing the immature promyelocytes to differentiate to normal mature blood cells thus decreasing promyelocytes.[citation needed]

Side effects

In dermatological use

When used, dryness or increased sensitivity to sunlight of the affected skin may occur.[14] More sensitive patients may also experience redness, scaling, itching, and burning.[15] A gradual increase in the frequency and amount of tretinoin application is best, as this allows one's skin to adequately adjust to the drug. Patients should be careful to follow their physician's recommendations when beginning a round of treatment.

As this product may cause irritation, it may indirectly increase sun sensitivity and fragility of the skin.[16] Patients who are using the drug should apply moisturizer and sunscreen to reduce the chance of developing sunburn while using tretinoin.[16] Additionally, patients using tretinoin should be cautious when simultaneously using other topical medications that contain salicylic acid, resorcinol, or sulfur because these medications may potentiate the drying and possibly irritating effects of tretinoin.[17] Topical tretinoin should be avoided during pregnancy because its use has been linked to birth defects in several case reports.[18]

In leukemia use

There is a unique complication of retinoic acid syndrome in patients with acute promyelocytic leukemia. This is associated with the development of dyspnea, fever, weight gain, peripheral edema and is treated with dexamethasone. The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes.

Teratogenicity

It is a teratogen, and therefore can cause birth defects and tests have shown increases in fetal skull abnormalities in rats.[19] Women who are or may be pregnant, or who are seeking to become pregnant, are therefore warned against using it.[20] This teratogenic effect is caused by the interference of the exogenous retinoic acid with endogenous retinoic acid signaling, which plays a role in patterning the developing embryo. However the risks of topical tretinoin to the fetus seems to be limited.[21]

Research uses

A study published by the European Respiratory Journal in 2002, suggested tretinoin can reverse the effects of emphysema in mice by returning elasticity (and regenerating lung tissue through gene mediation) to the alveoli.[22] Studies suggested this might form a promising treatment in human emphysema patients.[23] However, a newer follow-up study done in 2006 found inconclusive results ("no definitive clinical benefits") using vitamin A (retinoic acid) in treatment of emphysema in humans and stated further research is needed to reach conclusions on this treatment.[24]

Etymology and pronunciation

The name tretinoin comes from trans- + retinoic,[25] and the name isotretinoin is the same root plus the prefix iso-. The following variants apply equally to both words. Given that retinoic is pronounced /ˌrɛt[invalid input: 'ɨ']ˈnoʊ[invalid input: 'ɨ']k/,[25][26][27][28] it is natural that /ˌtrɛt[invalid input: 'ɨ']ˈnoʊ[invalid input: 'ɨ']n/ is a commonly heard pronunciation. Dictionary transcriptions also include /ˌtr[invalid input: 'ɨ']ˈtɪnoʊ.[invalid input: 'ɨ']n/[26][27] and /ˈtrɛt[invalid input: 'ɨ']nɔɪn/.[25][28]

File:Tube and Packaging of Tretinoin Cream.jpeg
A tube of Tretinoin cream and its packaging

Pricing

Retin-A Micro, which received FDA approval in January 2014 and Jublia, which received FDA approval in July 2014,[29] is one of a number of products that Valeant Pharmaceuticals International Inc acquired with the purchase of Dow Pharmaceuticals in 2008.[30] They also filled Retin-A Micro Tretinoin prescriptions.[30] They are sold through the specialty pharmacy Philidor Rx Services in the United States.[31]

See also

Footnotes

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "www.who.int" (PDF).
  3. ^ a b c d "Dr. James Fulton, co-creator of Retin-A and acne researcher, dies". Miami Herald. 2013-07-2013. Retrieved 2013-07-27. {{cite news}}: |first= missing |last= (help); Check date values in: |date= (help)
  4. ^ MedlinePlus Drug Information: Tretinoin Topical
  5. ^ Stefanaki C, Stratigos A, Katsambas A (June 2005). "Topical retinoids in the treatment of photoaging". J Cosmet Dermatol. 4 (2): 130–4. doi:10.1111/j.1473-2165.2005.40215.x. PMID 17166212.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Rogers, N and Avram, M (October 2008). "Medical treatments for male and female pattern hair loss". Journal of the American Academy of Dermatology. 59 (4): 547–566. doi:10.1016/j.jaad.2008.07.001. PMID 18793935.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Babamiri K, Nassab R. (Jan 2010). "Cosmeceuticals: the evidence behind the retinoids". Aesthetic Surgery Journal. 30 (1): 74–77. doi:10.1177/1090820X09360704. PMID 20442078.
  8. ^ Serri R, Iorizzo M. (Nov 2008). "Cosmeceuticals: focus on topical retinoids in photoaging". Clinics In Dermatology. 26 (6): 633–635. doi:10.1016/j.clindermatol.2007.09.016. PMID 18940544.
  9. ^ Arthur W. Perry (2007). Straight talk about cosmetic surgery. Yale University Press. p. 63. ISBN 978-0-300-12104-9.
  10. ^ Huang M, Ye Y, Chen S, Chai J, Lu J, Zhoa L, Gu L, Wang Z (1988). "Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia" (PDF). Blood. 72 (2): 567–72. PMID 3165295.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Castaigne S, Chomienne C, Daniel M, Ballerini P, Berger R, Fenaux P, Degos L (1990). "All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results" (PDF). Blood. 76 (9): 1704–9. PMID 2224119.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Sanz M (2006). "Treatment of acute promyelocytic leukemia" (PDF). Hematology Am Soc Hematol Educ Program. 2006 (1): 147–55. doi:10.1182/asheducation-2006.1.147. PMID 17124054.
  13. ^ Kakizuka A (August 1991). "Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARα with a novel putative transcription factor, PML". Cell. 6 (4): 663–74. doi:10.1016/0092-8674(91)90112-C.
  14. ^ Retin-A (Tretinoin)
  15. ^ Tretinoin Side Effects | Drugs.com
  16. ^ a b al.], edited by Brian K. Alldredge ... [et (2013). Applied therapeutics : the clinical use of drugs (10th ed.). Baltimore: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 948. ISBN 978-1609137137. {{cite book}}: |first1= has generic name (help)
  17. ^ Tretinoin [package insert]. Manati, Puerto Rico: Ortho Pharmaceutical; 2012.
  18. ^ Meredith, Fiona M.; Ormerod, Anthony D. (31 August 2013). "The Management of Acne Vulgaris in Pregnancy". American Journal of Clinical Dermatology. 14 (5): 351–358. doi:10.1007/s40257-013-0041-9.
  19. ^ Lee LM, Leung CY, Tang WW, Choi HL, Leung YC, McCaffery PJ, Wang CC, Woolf AS, Shum AS. (August 2012). "A paradoxical teratogenic mechanism for retinoic acid". Proc. Natl. Acad. Sci. U.S.A. 109 (34): 13668–73. doi:10.1073/pnas.1200872109. PMID 22869719.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ Tretinoin facts and comparisons at Drugs.com
  21. ^ Loureiro KD, Kao KK, Jones KL, Alvarado S, Chavez C, Dick L, Felix R, Johnson D, Chambers CD; Kao; Jones; Alvarado; Chavez; Dick; Felix; Johnson; Chambers (July 2005). "Minor malformations characteristic of the retinoic acid embryopathy and other birth outcomes in children of women exposed to topical tretinoin during early pregnancy". Am J Med Genet A. 136 (2): 117–21. doi:10.1002/ajmg.a.30744. PMID 15940677.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ "Vitamin may cure smoking disease". BBC News Online. December 22, 2003. Retrieved 2006-11-18.
  23. ^ Mao J, Goldin J, Dermand J, Ibrahim G, Brown M, Emerick A, McNitt-Gray M, Gjertson D, Estrada F, Tashkin D, Roth M; Goldin; Dermand; Ibrahim; Brown; Emerick; McNitt-Gray; Gjertson; Estrada; Tashkin; Roth (1 March 2002). "A pilot study of all-trans-retinoic acid for the treatment of human emphysema" (PDF). Am J Respir Crit Care Med. 165 (5): 718–23. doi:10.1164/ajrccm.165.5.2106123. PMID 11874821.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  24. ^ Roth M, Connett J, D'Armiento J, Foronjy R, Friedman P, Goldin J, Louis T, Mao J, Muindi J, O'Connor G, Ramsdell J, Ries A, Scharf S, Schluger N, Sciurba F, Skeans M, Walter R, Wendt C, Wise R; Connett; d'Armiento; Foronjy; Friedman; Goldin; Louis; Mao; Muindi; O'Connor; Ramsdell; Ries; Scharf; Schluger; Sciurba; Skeans; Walter; Wendt; Wise; Forte Study (2006). "Feasibility of retinoids for the treatment of emphysema study" (PDF). Chest. 130 (5): 1334–45. doi:10.1378/chest.130.5.1334. PMID 17099008.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  25. ^ a b c Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt.
  26. ^ a b Oxford Dictionaries, Oxford Dictionaries Online, Oxford University Press.
  27. ^ a b Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster.
  28. ^ a b Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier.
  29. ^ "Valeant Pharmaceuticals Announces Approval of Retin-A Micro® Microsphere 0.08%". Valeant Pharmaceuticals. Laval, Quebec. 31 January 2014. Retrieved 1 November 2015.
  30. ^ a b "Valeant Pharmaceuticals Announces FDA Approval Of Jublia® for the Treatment of Onychomycosis". Valeant Pharmaceuticals. Laval, Quebec. 9 June 2014. Retrieved 1 November 2015.
  31. ^ Rapoport, Michael (29 October 2015). "Valeant Countersues R&O Pharmacy Billing dispute draws attention to drug maker's work with specialty pharmacies". Retrieved 1 November 2015.
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