"ATRA" redirects here. For other uses, see ATRA (disambiguation).
Clinical data
Pronunciation See pronunciation note
Trade names Avita, Renova, Retin-a
AHFS/ Monograph
MedlinePlus a682437
License data
  • AU: X (High risk)
  • US: C (Risk not ruled out)
Routes of
Topical, by mouth
ATC code D10AD01 (WHO) L01XX14 (WHO)
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Protein binding > 95%
Biological half-life 0.5-2 hours
CAS Number 302-79-4 YesY
PubChem (CID) 444795
DrugBank DB00755 YesY
ChemSpider 392618 YesY
UNII 5688UTC01R YesY
KEGG D00094 YesY
ChEBI CHEBI:15367 YesY
Chemical and physical data
Formula C20H28O2
Molar mass 300.4412 g/mol
3D model (Jmol) Interactive image
Melting point 180 °C (356 °F)

Tretinoin is the pharmaceutical form of retinoic acid. One of several retinoids, it is the carboxylic acid form of vitamin A and is also known as all-trans retinoic acid (ATRA). It is a first generation topical retinoid commonly used topically to treat acne vulgaris. It is also used orally to treat acute promyelocytic leukemia (APL). 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.[1]

Medical uses

Skin disease

Tretinoin is most commonly used to treat acne.[2] It is also used off-label to treat and reduce the appearance of stretch marks by increasing collagen production in the dermis.[3]

In topical form, this drug is pregnancy category C and should not be used by pregnant women.[2]

People using the topical form should not also use any cream or lotion that has a strong drying effect, contains alcohol, astringents, spices, lime, sulfur, resorcinol, or aspirin, as these may interact with tretinoin or exacerbate its side effects.[2]


Tretinoin is used to induce remission in people with acute promyelocytic leukemia who have a mutation (the t(15;17) translocation 160 and/or the presence of the PML/RARα gene) and who don't respond to anthracyclines or can't take that class of drug. It is not used for maintenance therapy.[4][5][6]

In oral form, this drug is pregnancy category D and should not be used by pregnant women as it may harm the fetus.[4]

Side effects

Skin disease use

Topical tretinoin is only for use on skin and it should not be applied to eyes or mucosal tissues. Common side effects include skin irritation, redness, swelling, and blistering. Skin is more susceptible to sunburn.[2]

Leukemia use

The oral form of the drug has boxed warnings concerning the risks of retinoic acid syndrome and leukocytosis.[4]

Other significant side effects include a risk of thrombosis, benign intracranial hypertension in children, high lipids (hypercholesterolemia and/or hypertriglyceridemia), and liver damage.[4]

There are many significant side effects from this drug that include malaise (66%), shivering (63%), hemorrhage (60%), infections (58%), peripheral edema (52%), pain (37%), chest discomfort (32%), edema (29%), disseminated intravascular coagulation (26%), weight increase (23%), injection site reactions (17%), anorexia (17%), weight decrease (17%), and myalgia (14%).[4]

Respiratory side effects usually signify retinoic acid syndrome, and include upper respiratory tract disorders (63%), dyspnea (60%), respiratory insufficiency (26%), pleural effusion (20%), pneumonia (14%), rales (14%), and expiratory wheezing (14%), and many others at less than 10%.[4]

Around 23% of people taking the drug have reported eararche or a feeling of fullness in their ears.[4]

Gastrointestinal disorders include bleeding (34%), abdominal pain (31%), diarrhea (23%), constipation (17%), dyspepsia (14%), and swollen belly (11%) and many others at less than 10%.[4]

In the cardiovascular system, side effects include arrhythmias (23%), flushing (23%), hypotension (14%), hypertension (11%), phlebitis (11%), and cardiac failure (6%) and for 3% of patients: cardiac arrest, myocardial infarction, enlarged heart, heart murmur, ischemia, stroke, myocarditis, pericarditis, pulmonary hypertension, secondary cardiomyopathy.[4]

In the nervous system, side effects include dizziness (20%), paresthesias (17%), anxiety (17%), insomnia (14%), depression (14%), confusion (11%), and many others at less than 10% frequency.[4]

In the urinary system, side effects include renal insufficiency (11%) and several others at less than 10% frequency.[4]

Mechanism of action

For its use in cancer, its mechanism of action is unknown, but on a cellular level, laboratory test show that tretinoin forces APL cells to differentiate and stops them from proliferating; in people there is evidence that it forces the primary cancerous promyelocytes to differentiate into their final form, allowing normal cells to take over the bone marrow.[4]

For its use in acne, the mechanism is unknown, but again on a cellular level there is evidence that it decreases the ability of epithelial cells in hair follicles to stick together, leading to fewer blackheads; it also seems to make the epithelial cells divide faster, causing the blackheads to be pushed out.[2]


Tretinoin was co-developed for its use in acne by James Fulton and Albert Kligman when they were at University of Pennsylvania in the late 1960s.[7][8] The University of Pennsylvania held the patent for Retin-A, which it licensed to pharmaceutical companies.[8]


The origin of the name tretinoin is uncertain,[9][10] although several sources agree (one with probability,[9] one with asserted certainty[11]) that it probably comes from trans- + retinoic [acid] + -in, which is plausible given that tretinoin is the all-trans isomer of retinoic acid. The name isotretinoin is the same root tretinoin plus the prefix iso-. Regarding pronunciation, the following variants apply equally to both tretinoin and isotretinoin. Given that retinoic is pronounced /ˌrɛtˈnk/,[10][11][12][13] it is natural that /ˌtrɛtˈnn/ is a commonly heard pronunciation. Dictionary transcriptions also include /ˌtrˈtɪnn/ (trə-TIN-oh-in)[10][12] and /ˈtrɛtnɔɪn/.[11][13]


Tretinoin has been explored as a treatment for hair loss, potentially as a way to increase the ability of minoxidil to penetrate the scalp, but the evidence is weak and contradictory.[14][15]

See also


  1. "" (PDF).
  2. 1 2 3 4 5 Topical Cream Gel Liquid Label
  3. Arthur W. Perry (2007). Straight talk about cosmetic surgery. Yale University Press. p. 63. ISBN 978-0-300-12104-9.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 Oral Label
  5. 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.
  6. 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.
  7. Vivant Pharmaceuticals, LLC Press Release. July 10, 2013, Vivant Skin Care Co-founder James E. Fulton, MD, Loses Colon Cancer Battle
  8. 1 2 Denis Gellene for the New York Times. Feb 22, 2010. Dr. Albert M. Kligman, Dermatologist, Dies at 93
  9. 1 2 Merriam-Webster, Merriam-Webster's Unabridged Dictionary, Merriam-Webster.
  10. 1 2 3 Oxford Dictionaries, Oxford Dictionaries Online, Oxford University Press.
  11. 1 2 3 Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt.
  12. 1 2 Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster.
  13. 1 2 Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier.
  14. Ralph M. Trüeb. The Difficult Hair Loss Patient: Guide to Successful Management of Alopecia and Related Conditions. Springer, 2015. ISBN 9783319197012 Pg. 95
  15. Rogers, N; 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.

External links

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