Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Dutasteride: Difference between pages

{{Short description|Hormone replacement medication}}

{{Use dmy dates|date=March 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug

| Verifiedfields = verified

| Watchedfields = verified

| verifiedrevid = 461091686

| width = 250

| tradename = Avodart, others

| DailyMedID = Dutasteride

| pregnancy_category = Not to be used during pregnancy

| routes_of_administration = [[Oral administration|By mouth]]

| class = [[5α-Reductase inhibitor]]

| ATC_prefix = G04

| ATC_suffix = CB02

| ATC_supplemental =

| bioavailability = 60%<ref name="LemkeWilliams2008" />

| protein_bound = 99%<ref name="LemkeWilliams2008" />

| metabolism = [[Liver]] ([[CYP3A4]])<ref name="LemkeWilliams2008" />

| metabolites = • 4'-Hydroxydutasteride<ref name="LemkeWilliams2008" /><br />• 6'-Hydroxydutasteride<ref name="LemkeWilliams2008" /><br />• 1,2-Dihydrodutasteride<ref name="LemkeWilliams2008" /><br />(All three active)<ref name="LemkeWilliams2008" />

| elimination_half-life = 4–5 weeks<ref name="BurchumRosenthal2014" /><ref name=Blu2008 />

| excretion = [[Feces]]: 40% (metabolites)<ref name="LemkeWilliams2008" /><br />[[Urine]]: 5% (unchanged)<ref name="LemkeWilliams2008" />

| IUPHAR_ligand = 7457

| KEGG_Ref = {{keggcite|correct|kegg}}

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1200969

| synonyms = GG-745; GI-198745; GI-198745X; ''N''-[2,5-Bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide

<!--Chemical data-->

| IUPAC_name = (1S,3aS,3bS,5aR,9aR,9bS,11aS)-''N''-[2,5-bis(trifluoromethyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,9b,10,11-dodecahydroindeno[5,4-f]quinoline-1-carboxamide

| C=27 | H=30 | F=6 | N=2 | O=2

| SMILES = FC(F)(F)c1cc(c(cc1)C(F)(F)F)NC(=O)[C@@H]3[C@]2(CC[C@H]4[C@H]([C@@H]2CC3)CC[C@H]5NC(=O)\C=C/[C@]45C)C

<!-- Definition and medical uses -->

'''Dutasteride''', sold under the brand name '''Avodart''' among others, is a medication primarily used to treat the symptoms of a [[benign prostatic hyperplasia]] (BPH), an enlarged prostate not associated with cancer. A few months may be required before benefits occur.<ref name=BNF76/> It is also used for [[pattern hair loss|scalp hair loss]] in men and as a part of [[transgender hormone therapy (male-to-female)|hormone therapy]] in [[transgender women]].<ref name="ShapiroOtberg2015">{{cite book|vauthors=Shapiro J, Otberg N|title=Hair Loss and Restoration, Second Edition|url=https://books.google.com/books?id=bJG9BwAAQBAJ&pg=PA39|date=17 April 2015|publisher=CRC Press|isbn=978-1-4822-3199-1|pages=39–|access-date=27 October 2016|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112145741/https://books.google.com/books?id=bJG9BwAAQBAJ&pg=PA39|url-status=live}}</ref><ref name=Trans2017>{{cite journal | vauthors = Wesp LM, Deutsch MB | title = Hormonal and Surgical Treatment Options for Transgender Women and Transfeminine Spectrum Persons | journal = The Psychiatric Clinics of North America | volume = 40 | issue = 1 | pages = 99–111 | date = March 2017 | pmid = 28159148 | doi = 10.1016/j.psc.2016.10.006 }}</ref> It is usually taken by mouth.<ref name=AHFS2019>{{cite web |title=Dutasteride Monograph for Professionals |url=https://www.drugs.com/monograph/dutasteride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=18 March 2019 |language=en |archive-date=4 July 2019 |archive-url=https://web.archive.org/web/20190704111545/https://www.drugs.com/monograph/dutasteride.html |url-status=live }}</ref><ref name=Wu2013>{{cite journal | vauthors = Wu C, Kapoor A | title = Dutasteride for the treatment of benign prostatic hyperplasia | journal = Expert Opinion on Pharmacotherapy | volume = 14 | issue = 10 | pages = 1399–1408 | date = July 2013 | pmid = 23750593 | doi = 10.1517/14656566.2013.797965 | s2cid = 25041466 }}</ref><ref name=BNF76>{{cite book|title=British National Formulary : BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=769|edition=76}}</ref>

<!-- Side effects and mechanism -->

The most commonly reported side effects of dutasteride, although rare, include sexual dysfunction and [[depression (mood)|depression]].<ref name=AHFS2019/> In the largest available study of 6,729 men with BPH, 9% experienced erectile dysfunction (compared to 5.7% treated with a [[placebo]]), 3.3% experienced decreased [[libido|sex drive]] (vs 1.6% of placebo), and 1.9% had [[gynecomastia|enlarged breasts]] (vs 1% of placebo).<ref name="Fertig2007DOJ">{{cite journal | vauthors = Fertig RM, Gamret AC, Darwin E, Gaudi S | title = Sexual side effects of 5-α-reductase inhibitors finasteride and dutasteride: A comprehensive review | journal = Dermatology Online Journal | volume = 23 | issue = 11 | date = November 2017 | pmid = 29447628 | doi = 10.5070/D32311037240 | doi-access = free }}</ref><ref name="AndrioleREDUCE2010">{{cite journal | vauthors = Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, Pettaway CA, Tammela TL, Teloken C, Tindall DJ, Somerville MC, Wilson TH, Fowler IL, Rittmaster RS | title = Effect of dutasteride on the risk of prostate cancer | journal = The New England Journal of Medicine | volume = 362 | issue = 13 | pages = 1192–1202 | date = April 2010 | pmid = 20357281 | doi = 10.1056/NEJMoa0908127 | doi-access = free }}</ref> Exposure during [[pregnancy]] is specifically contraindicated because [[antiandrogen]]s such as dutasteride have been shown to interfere with the sexual development of male fetuses.<ref name=Blu2008>{{cite book|vauthors=Blume-Peytavi U, Whiting DA, Trüeb RM|title=Hair Growth and Disorders|url=https://books.google.com/books?id=pHrX2-huQCoC&pg=PA369|date=26 June 2008|publisher=Springer Science & Business Media|isbn=978-3-540-46911-7|pages=182, 369|access-date=10 December 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110031700/https://books.google.com/books?id=pHrX2-huQCoC&pg=PA369|url-status=live}}</ref><ref name=AHFS2019/>

<!-- History, society, and culture -->

Dutasteride was patented in 1993 by [[GlaxoSmithKline]] and was approved for medical use in 2001.<ref name=Fis2006>{{cite book |vauthors=Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=483 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA483 |language=en |access-date=2020-09-19 |archive-date=2023-01-10 |archive-url=https://web.archive.org/web/20230110031701/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA483 |url-status=live }}</ref><ref name=AHFS2019/> In the United States and elsewhere, it is available as a [[generic medication]].<ref name=BNF76/> In 2018, it was the 291st-most commonly prescribed medication in the US with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title = Dutasteride - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Dutasteride | access-date = 7 October 2022 | archive-date = 6 February 2020 | archive-url = https://web.archive.org/web/20200206154756/https://clincalc.com/DrugStats/Drugs/Dutasteride | url-status = live }}</ref>

==Medical uses==

===Benign prostatic hyperplasia and prostate cancer===

Dutasteride is used for treating BPH, colloquially known as an "enlarged prostate".<ref name=Wu2013 /><ref>{{cite journal | vauthors = Slater S, Dumas C, Bubley G | title = Dutasteride for the treatment of prostate-related conditions | journal = Expert Opinion on Drug Safety | volume = 11 | issue = 2 | pages = 325–330 | date = March 2012 | pmid = 22316171 | doi = 10.1517/14740338.2012.658040 | s2cid = 207487490 }}</ref> It is approved by the [[Food and Drug Administration (United States)|Food and Drug Administration]] (FDA) in the U.S. for this indication.<ref name="FDA">{{cite web | url = http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=021319&DrugName=AVODART&ActiveIngred=DUTASTERIDE&SponsorApplicant=GLAXOSMITHKLINE&ProductMktStatus=1&goto=Search.DrugDetails | title = Search Results for "DUTASTERIDE" | work = Drugs@FDA: FDA Approved Drug Products | access-date = 2016-10-29 | archive-date = 2021-08-29 | archive-url = https://web.archive.org/web/20210829124132/https://www.accessdata.fda.gov/scripts/cder/daf/ | url-status = live }}</ref> A 2010 [[Cochrane review]] found a 25–26% reduction in the risk of developing [[prostate cancer]] with 5α-reductase inhibitor [[chemoprophylaxis|chemoprevention]].<ref name="pmid20977593">{{cite journal | vauthors = Wilt TJ, Macdonald R, Hagerty K, Schellhammer P, Tacklind J, Somerfield MR, Kramer BS | title = 5-α-Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review | journal = BJU International | volume = 106 | issue = 10 | pages = 1444–1451 | date = November 2010 | pmid = 20977593 | doi = 10.1111/j.1464-410X.2010.09714.x | s2cid = 22178061 | doi-access = }}</ref>

===Scalp hair loss and excessive hair growth===

Dutasteride is approved for the treatment of male androgenetic alopecia in [[South Korea]] and [[Japan]] at a dosage of 0.5&nbsp;mg per day.<ref name="ShapiroOtberg2015" /><ref name="pmid27489426" /> Several studies have found it to induce hair regrowth in men more rapidly and to a greater extent than even the highest approved dosage of [[finasteride]].<ref name="ShapiroOtberg2015" /><ref name="pmid32279398">{{cite journal | vauthors = Dhurat R, Sharma A, Rudnicka L, Kroumpouzos G, Kassir M, Galadari H, Wollina U, Lotti T, Golubovic M, Binic I, Grabbe S, Goldust M | title = 5-Alpha reductase inhibitors in androgenetic alopecia: Shifting paradigms, current concepts, comparative efficacy, and safety | journal = Dermatologic Therapy | volume = 33 | issue = 3 | pages = e13379 | date = May 2020 | pmid = 32279398 | doi = 10.1111/dth.13379 | s2cid = 215748750 | doi-access = free }}</ref><ref name="pmid30863034">{{cite journal | vauthors = Zhou Z, Song S, Gao Z, Wu J, Ma J, Cui Y | title = The efficacy and safety of dutasteride compared with finasteride in treating men with androgenetic alopecia: a systematic review and meta-analysis | journal = Clinical Interventions in Aging | volume = 14 | pages = 399–406 | date = 2019 | pmid = 30863034 | pmc = 6388756 | doi = 10.2147/CIA.S192435 | doi-access = free }}</ref><ref name="pmid17110217">{{cite journal | vauthors = Olsen EA, Hordinsky M, Whiting D, Stough D, Hobbs S, Ellis ML, Wilson T, Rittmaster RS | title = The importance of dual 5alpha-reductase inhibition in the treatment of male pattern hair loss: results of a randomized placebo-controlled study of dutasteride versus finasteride | journal = Journal of the American Academy of Dermatology | volume = 55 | issue = 6 | pages = 1014–1023 | date = December 2006 | pmid = 17110217 | doi = 10.1016/j.jaad.2006.05.007 }}</ref> The superior effectiveness of dutasteride relative to finasteride for this indication is because the inhibition of 5α-reductase and consequent reduction of dihydrotestosterone (DHT) production within the hair follicles is more complete with dutasteride. Dutasteride is also used off-label in the treatment of female pattern hair loss.<ref name="pmid24017975" /><ref name="CarminaAzziz2019">{{cite journal | vauthors = Carmina E, Azziz R, Bergfeld W, Escobar-Morreale HF, Futterweit W, Huddleston H, Lobo R, Olsen E | title = Female Pattern Hair Loss and Androgen Excess: A Report From the Multidisciplinary Androgen Excess and PCOS Committee | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 104 | issue = 7 | pages = 2875–2891 | date = July 2019 | pmid = 30785992 | doi = 10.1210/jc.2018-02548 | doi-access = free }}</ref>

Other 5α-reductase inhibitors such as finasteride (a type 2 inhibitor) have been used [[Off-label use|off-label]] to treat excessive hair growth in women with [[hirsutism]].<ref name=Blu2008 /><ref name="Martin2018">{{cite journal | vauthors = Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, Shapiro J, Montori VM, Swiglo BA | title = Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 93 | issue = 4 | pages = 1105–1120 | date = April 2008 | pmid = 18252793 | doi = 10.1210/jc.2018-00241 | doi-access = free }}</ref> Since dutasteride is an inhibitor of both type 1 and 2 5α-reductases, it could theoretically be a more effective therapy for hirsutism. However, dutasteride is not recommended for this indication due to a lack of supportive clinical evidence and a substantial risk of birth defects in female patients who inadvertently become pregnant.<ref name="Martin2018"/><ref name="LebwohlHeymann2013">{{cite book|vauthors=Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I|title=Treatment of Skin Disease: Comprehensive Therapeutic Strategies|url=https://books.google.com/books?id=hRryAAAAQBAJ&pg=PA327|date=19 September 2013|publisher=Elsevier Health Sciences|isbn=978-0-7020-5236-1|pages=327–|access-date=10 December 2016|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112145741/https://books.google.com/books?id=hRryAAAAQBAJ&pg=PA327|url-status=live}}</ref>

===Transgender hormone therapy===

Dutasteride is sometimes used as a component of [[transgender hormone therapy (male-to-female)|hormone therapy]] for [[Trans woman|transgender women]] in combination with an [[estrogen (medication)|estrogen]] and/or another [[antiandrogen]] such as [[spironolactone]].<ref name="Trans2017" /> It may be useful for treating scalp hair loss or in those who have issues tolerating spironolactone.<ref name="Trans2017" />

===Available forms===

Dutasteride is provided in the form of soft, [[oil]]-filled [[gelatin]] [[capsule (pharmacy)|capsule]]s containing 0.5&nbsp;mg dutasteride each.<ref name="FDALabel" />

==Contraindications==

Women who are or who may become [[pregnancy|pregnant]] should not handle the drug. Dutasteride can cause [[birth defect]]s in male [[fetus]]es, specifically [[ambiguous genitalia]] and undermasculinization.<ref name="FDALabel" /><ref name="McVaryWelliver2016">{{cite book|vauthors=McVary KT, Welliver C|title=Treatment of Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia: Current methods, outcomes, and controversies, An Issue of Urologic Clinics of North America, E-Book|url=https://books.google.com/books?id=OkLUDAAAQBAJ&pg=PA396|date=12 August 2016|publisher=Elsevier Health Sciences|isbn=978-0-323-45994-5|pages=396–|access-date=10 December 2017|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112145741/https://books.google.com/books?id=OkLUDAAAQBAJ&pg=PA396|url-status=live}}</ref> This is due to its antiandrogenic effects similar to what is seen in [[5α-reductase deficiency]].<ref name="McVaryWelliver2016" /> For the same reason, women who are currently pregnant should never take dutasteride.<ref name="FDALabel" /> People taking dutasteride should not [[blood donation|donate blood]] to prevent birth defects if a pregnant woman receives blood and should also not donate blood for at least 6&nbsp;months after the cessation of treatment due to the drug's long [[elimination half-life]].<ref name="FDALabel"/>

Children and people with known significant [[hypersensitivity]] (e.g., serious [[skin reaction]]s, [[angioedema]]) to dutasteride should not take it.<ref name="FDALabel">{{cite web | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021319s023s025lbl.pdf | title = AVODART (dutasteride) Soft Gelatin Capsules Prescribing information | date = June 2011 | work = GlaxoSmithKline | publisher = U.S. Food and Drug Administration | author = <!--Staff writer(s); no by-line.--> | access-date = 15 September 2013 | archive-date = 7 March 2013 | archive-url = https://web.archive.org/web/20130307020555/http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021319s023s025lbl.pdf | url-status = live }}</ref>

==Adverse effects==

Dutasteride has overall been found to be [[tolerability|well tolerated]] in studies of both men and women, producing minimal [[side effect]]s.<ref name=Hirs2016>{{cite journal | vauthors = Hirshburg JM, Kelsey PA, Therrien CA, Gavino AC, Reichenberg JS | title = Adverse Effects and Safety of 5-alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review | journal = The Journal of Clinical and Aesthetic Dermatology | volume = 9 | issue = 7 | pages = 56–62 | date = July 2016 | pmid = 27672412 | pmc = 5023004 }}</ref> Adverse effects include [[headache]] and [[gastrointestinal discomfort]].<ref name=Hirs2016 /> Isolated reports of [[menstruation|menstrual]] changes, [[acne]], and [[dizziness]] also exist.<ref name=Hirs2016 /> A small risk of sexual side effects has been documented in men taking the drug during the first few months of therapy.<ref name=Hirs2016 /><ref name="pmid27784557">{{cite journal | vauthors = Trost L, Saitz TR, Hellstrom WJ | title = Side Effects of 5-Alpha Reductase Inhibitors: A Comprehensive Review | journal = Sexual Medicine Reviews | volume = 1 | issue = 1 | pages = 24–41 | date = May 2013 | pmid = 27784557 | doi = 10.1002/smrj.3 }}</ref>

The FDA added a [[boxed warning|black-box warning]] to dutasteride in 2011 describing an increased risk of high-grade prostate cancer in those who take the drug.<ref>{{Cite web|url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-5-alpha-reductase-inhibitors-5-aris-may-increase-risk-more-serious|title=FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer|newspaper=U.S. Food and Drug Administration|date=18 June 2019|access-date=9 March 2021|archive-date=9 March 2021|archive-url=https://web.archive.org/web/20210309192037/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-5-alpha-reductase-inhibitors-5-aris-may-increase-risk-more-serious|url-status=live}}</ref> No direct mechanistic link between 5α-reductase inhibitors and prostate cancer has been established.<ref name="AUAGuideline2021"/> This is not due to a direct link between dutasteride or other 5α-reductase inhibitors and cancer ''per se'', but rather that those who take 5α-reductase inhibitors may have a decrease in [[prostate-specific antigen]] (PSA) levels, and therefore increases in PSA (which are an indicator of possible cancer) may be masked in those who take the drug.<ref name="Sarkar2019">{{cite journal | vauthors = Sarkar RR, Parsons JK, Bryant AK, Ryan ST, Kader AK, McKay RR, D'Amico AV, Nguyen PL, Hulley BJ, Einck JP, Mundt AJ, Kane CJ, Murphy JD, Rose BS | title = Association of Treatment With 5α-Reductase Inhibitors With Time to Diagnosis and Mortality in Prostate Cancer | journal = JAMA Internal Medicine | volume = 179 | issue = 6 | pages = 812–819 | date = June 2019 | pmid = 31058923 | pmc = 6503564 | doi = 10.1001/jamainternmed.2019.0280 }}</ref> This is thought to delay cancer diagnosis so that patients taking 5α-reductase inhibitors present with a [[Grading (tumors)|higher-grade]] tumor at the time of diagnosis. The [[American Urological Association]] <!-- (AUA) --> advises that increased risk for patients taking these drugs leads to higher prostate cancer-specific and [[Mortality rate|all-cause mortality]].<ref name="AUAGuideline2021">{{cite journal | vauthors = Lerner LB, McVary KT, Barry MJ, Bixler BR, Dahm P, Das AK, Gandhi MC, Kaplan SA, Kohler TS, Martin L, Parsons JK, Roehrborn CG, Stoffel JT, Welliver C, Wilt TJ | title = Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART I-Initial Work-up and Medical Management | journal = The Journal of Urology | volume = 206 | issue = 4 | pages = 806–817 | date = October 2021 | pmid = 34384237 | doi = 10.1097/JU.0000000000002183 | s2cid = 236999299 }}</ref> The AUA also advises that this affect can be alleviated with more frequent screening and lower PSA cutoffs for diagnostic biopsies in men taking dutasteride or other 5α-reductase inhibitors.<ref name="AUAGuideline2021"/> Dutasteride is known to reduce the growth and prevalence of benign prostate tumors.<ref name="Walsh2010">{{cite journal | vauthors = Walsh PC | title = Chemoprevention of prostate cancer | journal = The New England Journal of Medicine | volume = 362 | issue = 13 | pages = 1237–1238 | date = April 2010 | pmid = 20357287 | doi = 10.1056/NEJMe1001045 }}</ref> A 2018 [[meta-analysis]] found no higher risk of [[breast cancer]] with 5α-reductase inhibitors.<ref name="pmid29697934">{{cite journal | vauthors = Wang J, Zhao S, Luo L, Li E, Li X, Zhao Z | title = 5-alpha Reductase Inhibitors and risk of male breast cancer: a systematic review and meta-analysis | journal = International Braz J Urol | volume = 44 | issue = 5 | pages = 865–873 | date = 2018 | pmid = 29697934 | pmc = 6237523 | doi = 10.1590/S1677-5538.IBJU.2017.0531 }}</ref>

[[Sexual dysfunction|Sexual]] and mood side effects, such as erectile dysfunction,<ref name="Fertig2017">{{cite journal | vauthors = Fertig R, Shapiro J, Bergfeld W, Tosti A | title = Investigation of the Plausibility of 5-Alpha-Reductase Inhibitor Syndrome | journal = Skin Appendage Disorders | volume = 2 | issue = 3–4 | pages = 120–129 | date = January 2017 | pmid = 28232919 | pmc = 5264352 | doi = 10.1159/000450617 }}</ref> [[loss of libido]],<ref name="Traish2015">{{cite journal | vauthors = Traish AM, Melcangi RC, Bortolato M, Garcia-Segura LM, Zitzmann M | title = Adverse effects of 5α-reductase inhibitors: What do we know, don't know, and need to know? | journal = Reviews in Endocrine & Metabolic Disorders | volume = 16 | issue = 3 | pages = 177–198 | date = September 2015 | pmid = 26296373 | doi = 10.1007/s11154-015-9319-y | s2cid = 25002351 }}</ref> [[depression (mood)|depression]],<ref name=Tra2011>{{cite journal | vauthors = Traish AM, Hassani J, Guay AT, Zitzmann M, Hansen ML | title = Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients | journal = The Journal of Sexual Medicine | volume = 8 | issue = 3 | pages = 872–884 | date = March 2011 | pmid = 21176115 | doi = 10.1111/j.1743-6109.2010.02157.x }}</ref> and [[hypospermia|reduced semen volume]] occur in as many as 4.8% of patients taking 5α-reductase inhibitors including dutasteride.<ref name="pmid24955220">{{cite journal | vauthors = Traish AM, Mulgaonkar A, Giordano N | title = The dark side of 5α-reductase inhibitors' therapy: sexual dysfunction, high Gleason grade prostate cancer and depression | journal = Korean Journal of Urology | volume = 55 | issue = 6 | pages = 367–379 | date = June 2014 | pmid = 24955220 | pmc = 4064044 | doi = 10.4111/kju.2014.55.6.367 }}</ref><ref name="Traish2015"/> In affected men, semen volume is decreased an average of 30%,<ref name="Samaplaski 2013">{{cite journal | vauthors = Samplaski MK, Lo K, Grober E, Jarvi K | title = Finasteride use in the male infertility population: effects on semen and hormone parameters | journal = Fertility and Sterility | volume = 100 | issue = 6 | pages = 1542–1546 | date = December 2013 | pmid = 24012200 | doi = 10.1016/j.fertnstert.2013.07.2000 | doi-access = free }}</ref> with a smaller subgroup of patients also experiencing a decrease of sperm motility of 6-12%.<ref name="Amory2007">{{cite journal | vauthors = Amory JK, Wang C, Swerdloff RS, Anawalt BD, Matsumoto AM, Bremner WJ, Walker SE, Haberer LJ, Clark RV | title = The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 92 | issue = 5 | pages = 1659–1665 | date = May 2007 | pmid = 17299062 | doi = 10.1210/jc.2006-2203 }}</ref><ref name="Millsop2013"/> Sperm shape and function are unaffected and the impact on male fertility is unknown.<ref name="Semet2017">{{cite journal | vauthors = Semet M, Paci M, Saïas-Magnan J, Metzler-Guillemain C, Boissier R, Lejeune H, Perrin J | title = The impact of drugs on male fertility: a review | journal = Andrology | volume = 5 | issue = 4 | pages = 640–663 | date = July 2017 | pmid = 28622464 | doi = 10.1111/andr.12366 | s2cid = 37989045 | doi-access = free }}</ref> These negative effects reverse by 3–4 months after discontinuation of the drug.<ref name="Semet2017"/><ref name="Millsop2013">{{cite journal | vauthors = Millsop JW, Heller MM, Eliason MJ, Murase JE | title = Dermatological medication effects on male fertility | journal = Dermatologic Therapy | volume = 26 | issue = 4 | pages = 337–346 | date = July 2013 | pmid = 23914891 | doi = 10.1111/dth.12069 | s2cid = 9087715 | doi-access = free }}</ref><ref name="AUAGuideline2021"/>

In a study of 6,729 men with [[benign prostatic hyperplasia]] (BPH, a condition where the prostate grows unnassociated with [[prostate cancer|cancer]]), 9% had [[erectile dysfunction]] (compared to 5.7% treated with a [[placebo]]), 3.3% experienced decreased [[libido|sex drive]] (vs 1.6% of placebo), and 1.9% had [[gynecomastia|enlarged breasts]] (vs 1% of placebo).<ref name="Fertig2017"/><ref name="AndrioleREDUCE2010"/> These effects were noted to resolve over time, with many fewer men reporting any adverse effects by the end of the 4-year study.<ref name="AndrioleREDUCE2010"/><ref name="Fertig2017"/> The rate of discontinuation of the drug due to adverse effects was less than 5%.<ref name="AndrioleREDUCE2010"/>

A subset of men affected by sexual and mood side effects report persistent loss of libido,<ref name="Fertig2017"/> depression,<ref name=Hirs2016 /> and erectile dysfunction for several years after discontinuing treatment.<ref name="Traish2015"/> This remains a highly contested topic in the academic literature due to disagreements about whether the [[nocebo]] effect may play a role,<ref name="ThanRodriguezKhera2018">{{cite journal | vauthors = Than JK, Rodriguez K, Khera M | title = Post-finasteride Syndrome: A Review of Current Literature | journal = Current Sexual Health Reports | date = 24 July 2018 | volume = 10 | issue = 3 | pages = 152–157 | issn = 1548-3584 | eissn = 1548-3592 | doi = 10.1007/s11930-018-0163-4 | pmid = | s2cid = 81968700 | url = }}</ref><ref name="SaengmearnuparpLojanapiwatChattipakorn2021">{{cite journal | vauthors = Saengmearnuparp T, Lojanapiwat B, Chattipakorn N, Chattipakorn S | title = The connection of 5-alpha reductase inhibitors to the development of depression | journal = Biomedicine & Pharmacotherapy | volume = 143 | pages = 112100 | date = November 2021 | pmid = 34479019 | doi = 10.1016/j.biopha.2021.112100 | doi-access = free }}</ref><ref name="Coskuner2019">{{cite journal | vauthors = Coskuner ER, Ozkan B, Culha MG | title = Sexual Problems of Men With Androgenic Alopecia Treated With 5-Alpha Reductase Inhibitors | journal = Sexual Medicine Reviews | volume = 7 | issue = 2 | pages = 277–282 | date = April 2019 | pmid = 30301703 | doi = 10.1016/j.sxmr.2018.07.003 | s2cid = 52946784 }}</ref> whether self-report questionnaires are reliable for this data,<ref name="AUAGuideline2021"/> and whether enough objective evidence exists to conclude these effects are persistent after discontinuation of the drug.<ref name="AUAGuideline2021"/><ref name="Traish 2020">{{cite journal | vauthors = Traish AM | title = Post-finasteride syndrome: a surmountable challenge for clinicians | journal = Fertility and Sterility | volume = 113 | issue = 1 | pages = 21–50 | date = January 2020 | pmid = 32033719 | doi = 10.1016/j.fertnstert.2019.11.030 | s2cid = 211064052 | doi-access = free }}</ref><ref name="Liu2016">{{cite journal | vauthors = Liu L, Zhao S, Li F, Li E, Kang R, Luo L, Luo J, Wan S, Zhao Z | title = Effect of 5α-Reductase Inhibitors on Sexual Function: A Meta-Analysis and Systematic Review of Randomized Controlled Trials | journal = The Journal of Sexual Medicine | volume = 13 | issue = 9 | pages = 1297–1310 | date = September 2016 | pmid = 27475241 | doi = 10.1016/j.jsxm.2016.07.006 }}</ref> The Post-Finasteride Syndrome Foundation (PFSF) was created with a medical advisory board to study the topic (finasteride is a similar 5α-reductase inhibitor)<ref>{{Cite web|title=The Post-Finasteride Syndrome Foundation – Dedicated to supporting research and finding treatments for PFS patients worldwide.|url=https://www.pfsfoundation.org/|access-date=2021-12-24|language=en-US|archive-date=2021-12-21|archive-url=https://web.archive.org/web/20211221100527/https://www.pfsfoundation.org/|url-status=live}}</ref> and lawsuits alleging harm from the drug are ongoing.<ref>{{Cite news |vauthors=Pierson B |date=2021-09-08 |title=Group sues to have hair-loss drug Propecia pulled from market |language=en |work=Reuters |url=https://www.reuters.com/legal/litigation/group-sues-have-hair-loss-drug-propecia-pulled-market-2021-09-08/ |access-date=2021-12-24 |archive-date=2021-12-24 |archive-url=https://web.archive.org/web/20211224165809/https://www.reuters.com/legal/litigation/group-sues-have-hair-loss-drug-propecia-pulled-market-2021-09-08/ |url-status=live }}</ref> Concerns from the PFSF and other patient advocates led the FDA to add a black-box warning to Finasteride for possible risks of suicide in June 2022.<ref name="AUAGuideline2021"/><ref name="Levine2022Reuters">{{cite news |vauthors=Levine D |title=FDA requires disclosure of suicide risk for anti-baldness drug |url=https://www.reuters.com/business/healthcare-pharmaceuticals/fda-requires-disclosure-suicide-risk-anti-baldness-drug-2022-06-10/ |access-date=12 November 2022 |work=Reuters |date=10 June 2022 |language=en |archive-date=12 November 2022 |archive-url=https://web.archive.org/web/20221112200941/https://www.reuters.com/business/healthcare-pharmaceuticals/fda-requires-disclosure-suicide-risk-anti-baldness-drug-2022-06-10/ |url-status=live }}</ref> Some experts have questioned the basis of the black-box warning, given that it relies on anecdotal patient-reported outcomes rather than prospective trials.<ref name="AUAGuideline2021"/>

==Overdose==

No specific [[antidote]] for [[overdose]] of dutasteride is known, since the drug is extremely safe and well tolerated. Research studies show that even at 100 times the normal dose, dutasteride is not lethal.<ref name="Avodart-Label">{{cite web |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021319s028s029lbl.pdf |title=AVODART (dutasteride) Soft Gelatin Capsules Prescribing information |work=GlaxoSmithKline |publisher=U.S. Food and Drug Administration |access-date=2020-01-10 |archive-date=2021-04-03 |archive-url=https://web.archive.org/web/20210403220821/https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021319s028s029lbl.pdf |url-status=live }}</ref> Treatment of dutasteride overdose should be based on [[symptom]]s and should be with supportive therapies.<ref name="Avodart-Label" /> The long elimination half-life of dutasteride should be taken into consideration in the event of an overdose of the medication.<ref name="Avodart-Label" /> Dutasteride has been used in clinical studies at doses of up to 40&nbsp;mg/day for a week (80&nbsp;times the therapeutic dosage) and 5&nbsp;mg/day for 6&nbsp;months (10&nbsp;times the therapeutic dosage) with no significant [[drug safety|safety]] concerns or additional side effects.<ref name="Avodart-Label" />

== Current investigations ==

Dutasteride has been studied in combination with [[bicalutamide]] in the treatment of prostate cancer.<ref name="pmid26048455">{{cite journal | vauthors = Chu FM, Sartor O, Gomella L, Rudo T, Somerville MC, Hereghty B, Manyak MJ | title = A randomised, double-blind study comparing the addition of bicalutamide with or without dutasteride to GnRH analogue therapy in men with non-metastatic castrate-resistant prostate cancer | journal = European Journal of Cancer | volume = 51 | issue = 12 | pages = 1555–1569 | date = August 2015 | pmid = 26048455 | doi = 10.1016/j.ejca.2015.04.028 }}</ref><ref name="pmid26702991">{{cite journal | vauthors = Gaudet M, Vigneault É, Foster W, Meyer F, Martin AG | title = Randomized non-inferiority trial of Bicalutamide and Dutasteride versus LHRH agonists for prostate volume reduction prior to I-125 permanent implant brachytherapy for prostate cancer | journal = Radiotherapy and Oncology | volume = 118 | issue = 1 | pages = 141–147 | date = January 2016 | pmid = 26702991 | doi = 10.1016/j.radonc.2015.11.022 }}</ref><ref name="pmid27330919">{{cite journal | vauthors = Dijkstra S, Witjes WP, Roos EP, Vijverberg PL, Geboers AD, Bruins JL, Smits GA, Vergunst H, Mulders PF | title = The AVOCAT study: Bicalutamide monotherapy versus combined bicalutamide plus dutasteride therapy for patients with locally advanced or metastatic carcinoma of the prostate-a long-term follow-up comparison and quality of life analysis | journal = SpringerPlus | volume = 5 | pages = 653 | year = 2016 | pmid = 27330919 | pmc = 4870485 | doi = 10.1186/s40064-016-2280-8 | doi-access = free }}</ref>

Ongoing clinical trials are investigating whether dutasteride may be an effective treatment for [[premenstrual dysphoric disorder]] (PMDD), because dutasteride may inhibit the conversion of [[progesterone]] to [[allopregnanolone]], a [[neurosteroid]] [[metabolite]], which may be responsible for some of the debilitating symptoms of PMDD.<ref name="pmid26766596">{{cite journal | vauthors = Pearlstein T | title = Treatment of Premenstrual Dysphoric Disorder: Therapeutic Challenges | journal = Expert Review of Clinical Pharmacology | volume = 9 | issue = 4 | pages = 493–496 | date = April 2016 | pmid = 26766596 | doi = 10.1586/17512433.2016.1142371 | quote = A recent study with a 5α-reductase inhibitor dutasteride, that blocks the conversion of progesterone to ALLO, reported that dutasteride 2.5 mg daily decreased several premenstrual symptoms | doi-access = free }}</ref><ref name="PsychBullNaguy2022">{{cite journal | vauthors = Naguy A, El-Sheshai A, Thiguti SH, Alamiri B | title = Psychopharmacotherapy of Premenstrual Dysphoric Disorder-''New Vistas'' | journal = Psychopharmacology Bulletin | volume = 52 | issue = 3 | pages = 81–83 | date = June 2022 | pmid = 35815174 | pmc = 9235312 | quote = Capitalizing on this premise, agents in the pipeline for PMDD including dutasteride, ulipristal acetate, and sepranolone are promising. Dutasteride, FDA-approved for benign prostatic hyperplasia, is a 5-α reductase inhibitor; the latter catalyzes the rate-limiting step in metabolism of progesterone to allopregnanolone...Two double-blind RCTs, cross-over trials, support use of dutasteride where high-dose (2.5 mg/d) outperforms placebo. }}</ref>

==Pharmacology==

===Pharmacodynamics===

Dutasteride belongs to a class of drugs called 5α-reductase inhibitors, which block the action of the 5α-reductase enzymes that convert testosterone into DHT.<ref name="BostwickCheng2014">{{cite book| vauthors = Bostwick DG, Cheng L |title= Urologic Surgical Pathology|url=https://books.google.com/books?id=wrHQAgAAQBAJ&pg=PA492|date=24 January 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-08619-6|pages=492–}}</ref> It [[enzyme inhibitor|inhibit]]s all three [[isozyme|form]]s of 5α-reductase, and can decrease DHT levels in the blood by up to 98%.<ref name="LemkeWilliams2008">{{cite book|vauthors=Lemke TL, Williams DA|title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1286|year=2008|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-6879-5|pages=1286–1287|access-date=2017-12-06|archive-date=2023-01-10|archive-url=https://web.archive.org/web/20230110031700/https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA1286|url-status=live}}</ref><ref name="Yamana2010">{{cite journal | vauthors = Yamana K, Labrie F, Luu-The V | title = Human type 3 5α-reductase is expressed in peripheral tissues at higher levels than types 1 and 2 and its activity is potently inhibited by finasteride and dutasteride | journal = Hormone Molecular Biology and Clinical Investigation | volume = 2 | issue = 3 | pages = 293–299 | date = August 2010 | pmid = 25961201 | doi = 10.1515/hmbci.2010.035 | s2cid = 28841145 }}</ref><ref name="Bradbury2007">{{cite book| vauthors = Bradbury R |title=Cancer|url=https://books.google.com/books?id=fdtDAAAAQBAJ&pg=PA49|date=30 January 2007|publisher=Springer Science & Business Media|isbn=978-3-540-33120-9|pages=49–}}</ref> Specifically it is a [[competitive inhibition|competitive]], [[suicide inhibition|mechanism-based]] ([[irreversible inhibition|irreversible]]) inhibitor of all three [[isoform]]s of 5α-reductase, [[SRD5A1|types I]], [[SRD5A2|II]], and [[SRD5A3|III]] ({{abbrlink|IC₅₀|Half-maximal inhibitory concentration}} values are 3.9&nbsp;nM for type I and 1.8&nbsp;nM for type II).<ref name="LemkeWilliams2008" /><ref name="Yamana2010" /><ref name="pmid18318566">{{cite journal | vauthors = Keam SJ, Scott LJ | title = Dutasteride: a review of its use in the management of prostate disorders | journal = Drugs | volume = 68 | issue = 4 | pages = 463–485 | year = 2008 | pmid = 18318566 | doi = 10.2165/00003495-200868040-00008 | s2cid = 242987808 }}</ref><ref name="pmid9871428">{{cite journal | vauthors = Gisleskog PO, Hermann D, Hammarlund-Udenaes M, Karlsson MO | title = A model for the turnover of dihydrotestosterone in the presence of the irreversible 5 alpha-reductase inhibitors GI198745 and finasteride | journal = Clinical Pharmacology and Therapeutics | volume = 64 | issue = 6 | pages = 636–647 | date = December 1998 | pmid = 9871428 | doi = 10.1016/S0009-9236(98)90054-6 | s2cid = 42901328 }}</ref> This is in contrast to finasteride, which is similarly an irreversible inhibitor of 5α-reductase but only inhibits the type II and III [[isoenzyme]]s.<ref name="pmid9871428" /><ref name="KeserüSwinney2015">{{cite book| vauthors = Keserü G, Swinney DC |title=Thermodynamics and Kinetics of Drug Binding|url=https://books.google.com/books?id=7WpICgAAQBAJ&pg=PA165|date=28 July 2015|publisher=Wiley|isbn=978-3-527-67304-9|pages=165–}}</ref><ref name="Yamana2010" /> As a result of this difference, dutasteride is able to achieve a reduction in circulating DHT levels of up to 98%, whereas finasteride is able to achieve a reduction of only 65 to 70%.<ref name="Bradbury2007"/><ref name="BurchumRosenthal2014" /><ref name="BostwickCheng2014" /><ref name="HeesakkersChapple2016">{{cite book| vauthors = Heesakkers J, Chapple C, De Ridder D, Farag F |title=Practical Functional Urology|url=https://books.google.com/books?id=aWKhCwAAQBAJ&pg=PA280|date=24 February 2016|publisher=Springer|isbn=978-3-319-25430-2|pages=280–}}</ref> In spite of the differential reduction in circulating DHT levels, the two drugs decrease levels of DHT to a similar extent of approximately 85 to 90% in the [[prostate gland]],<ref name="HeesakkersChapple2016" /> where the type II isoform predominates.<ref name="pmid18318566" />

Since 5α-reductases degrade testosterone to DHT, the inhibition of these enzymes could theoretically cause an increase in testosterone. A 2018 review found that initiation of 5α-reductase inhibitors did not result in a consistent increase in testosterone levels.<ref name="Traish2019">{{cite journal | vauthors = Traish AM, Krakowsky Y, Doros G, Morgentaler A | title = Do 5α-Reductase Inhibitors Raise Circulating Serum Testosterone Levels? A Comprehensive Review and Meta-Analysis to Explaining Paradoxical Results | journal = Sexual Medicine Reviews | volume = 7 | issue = 1 | pages = 95–114 | date = January 2019 | pmid = 30098986 | doi = 10.1016/j.sxmr.2018.06.002 | s2cid = 51968365 | doi-access = }}</ref> Among the studies analyzed, there was no statistically significant change in testosterone levels from 5α-reductase inhibitors overall, though men with lower baseline testosterone levels did show an increase.<ref name="Traish2019"/>

In addition to inhibition of DHT production, 5α-reductase inhibitors such as dutasteride are also [[neurosteroidogenesis inhibitor]]s, preventing the 5α-reductase-mediated biosynthesis of various neurosteroids, including allopregnanolone (from progesterone), {{abbrlink|THDOC|tetrahydrodeoxycorticosterone}} (from [[deoxycorticosterone]]), and [[3α-androstanediol]] (from testosterone).<ref name="pmid24955220"/> These neurosteroids are potent [[positive allosteric modulator]]s of the [[GABAA receptor|GABA_A receptor]] and have shown [[antidepressant]], [[anxiolytic]], and [[human sexual behavior|pro-sexual]] effects in [[animal research]].<ref name="pmid24955220" /><ref name="Weizman2008">{{cite book| vauthors = Weizman A |title=Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment|url=https://books.google.com/books?id=uABKkFdPjhkC|date=1 February 2008|publisher=Springer Science & Business Media|isbn=978-1-4020-6854-6}}</ref><ref name="TvrdeićPoljak2016">{{cite journal| vauthors = Tvrdeić A, Poljak L |title=Neurosteroids, GABAA receptors and neurosteroid based drugs: are we witnessing the dawn of the new psychiatric drugs?|journal=Endocrine Oncology and Metabolism |volume=2 |issue=1 |year=2016 |pages=60–71 |doi=10.21040/eom/2016.2.7|doi-broken-date=1 July 2024 |doi-access=free}}</ref> For this reason, decreased neurosteroid production is one hypothesized mechanism for sexual dysfunction and depression associated with 5α-reductase inhibitors such as dutasteride.<ref name="pmid24955220" />

===Pharmacokinetics===

The oral [[bioavailability]] of dutasteride is about 60%.<ref name="LemkeWilliams2008" /> Consumption with food does not adversely affect its [[absorption (pharmacokinetics)|absorption]].<ref name="LemkeWilliams2008" /> [[Cmax (pharmacology)|Peak plasma levels]] occur 2 to 3&nbsp;hours after administration.<ref name="LemkeWilliams2008" /> Dutasteride is present in [[semen]] at levels up to 3&nbsp;ng/ml, with no significant effects on DHT levels of sexual partners.<ref name="LemkeWilliams2008" /> The drug is extensively [[metabolism|metabolized]] in the [[liver]] by ''[[CYP3A4]]''.<ref name="LemkeWilliams2008" /> It has three major metabolites: 6'-hydroxydutasteride, 4'-hydroxydutasteride, and 1,2-dihydrodutasteride. The former two are formed by ''CYP3A4'', while the latter is not.<ref name="LemkeWilliams2008" /> All three metabolites are active; 6'-hydroxydutasteride has similar 5α-reductase inhibitor [[potency (pharmacology)|potency]] as dutasteride, while the other two are less potent.<ref name="LemkeWilliams2008" /> Dutasteride has an extremely long [[terminal half-life|terminal]] or elimination half-life of about 4 to 5&nbsp;weeks.<ref name="BurchumRosenthal2014">{{cite book|vauthors=Burchum J, Rosenthal L|title=Lehne's Pharmacology for Nursing Care|url=https://books.google.com/books?id=C7_NBQAAQBAJ&pg=PA803|date=2 December 2014|publisher=Elsevier Health Sciences|isbn=978-0-323-34026-7|pages=803–|access-date=27 October 2016|archive-date=12 January 2023|archive-url=https://web.archive.org/web/20230112145742/https://books.google.com/books?id=C7_NBQAAQBAJ&pg=PA803|url-status=live}}</ref><ref name=Blu2008 /> Its elimination half-life is increased in the elderly (170&nbsp;hours for men aged 20–49&nbsp;years, 300&nbsp;hours for men aged >70&nbsp;years).<ref name="LemkeWilliams2008" /> No dosage adjustment is necessary in the elderly nor in patients with [[renal impairment]].<ref name="LemkeWilliams2008" /> Because of its long elimination half-life, dutasteride requires 5 to 6&nbsp;months to reach [[steady state (pharmacokinetics)|steady-state]] concentrations.<ref name="pmid18318566" /> It also remains in the body for a long time after discontinuation and can be detected up to 4 to 6&nbsp;months.<ref name="LemkeWilliams2008" /><ref name="BurchumRosenthal2014" /> In contrast to dutasteride, finasteride has a short terminal half-life of only 5 to 8&nbsp;hours.<ref name=Blu2008 /><ref name="LemkeWilliams2008" /> Dutasteride is [[elimination (pharmacology)|eliminated]] mainly in the [[feces]] (40%) as metabolites.<ref name="LemkeWilliams2008" /> A smaller portion (5%) is eliminated unchanged in the [[urine]].<ref name="LemkeWilliams2008" />

==Chemistry==

{{See also|List of 5α-reductase inhibitors}}

Dutasteride, also known as ''N''-[2,5-bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, is a [[synthetic compound|synthetic]] [[androstane]] [[steroid]] and a [[4-azasteroid]].<ref name="LemkeWilliams2012">{{cite book| vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1381|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=1381–}}</ref><ref name="Ravina2011">{{cite book| vauthors = Ravina E |title=The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs|url=https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA183|date=11 January 2011|publisher=John Wiley & Sons|isbn=978-3-527-32669-3|pages=183–}}</ref> It is an [[structural analog|analogue]] of finasteride in which the ''tert''-butyl amide [[moiety (chemistry)|moiety]] has been replaced with a 2,5-''bis''(trifluoromethyl)phenyl [[functional group|group]].<ref name="Ravina2011" />

==History==

Dutasteride was [[patent]]ed in 1996 and was first described in the [[scientific literature]] in 1997.<ref name="Drugs.com" /><ref name="Llewellyn2011" /> It was approved by the FDA for the treatment of BPH in November 2001, and was introduced on the United States market the following year under the brand name Avodart.<ref name="Llewellyn2011" /> Dutasteride has subsequently been introduced in many other countries, including throughout Europe and South America.<ref name="Llewellyn2011">{{cite book|vauthors=Llewellyn W|title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC&pg=PT971|year=2011|publisher=Molecular Nutrition Llc|isbn=978-0-9828280-1-4|pages=968–,971–|access-date=2017-12-11|archive-date=2023-01-12|archive-url=https://web.archive.org/web/20230112145743/https://books.google.com/books?id=afKLA-6wW0oC&pg=PT971|url-status=live}}</ref> The [[patent protection]] of dutasteride expired in November 2015, so the drug has since become available in the United States in a variety of low-cost [[generic drug|generic formulation]]s.<ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/availability/generic-avodart.html|title=Generic Avodart Availability|website=Drugs.com|access-date=2016-12-10|archive-date=2016-12-20|archive-url=https://web.archive.org/web/20161220231141/https://www.drugs.com/availability/generic-avodart.html|url-status=live}}</ref>

It was approved for the treatment of scalp hair loss in South Korea in 2009 and in Japan in 2015.<ref>{{cite web|vauthors=MacDonald G|title=GSK Japan delays alopecia drug launch after Catalent manufacturing halt|date=3 December 2015|url=http://www.in-pharmatechnologist.com/Regulatory-Safety/GSK-Japan-delays-alopecia-drug-launch-after-Catalent-manufacturing-halt|access-date=14 June 2017|archive-date=1 October 2016|archive-url=https://web.archive.org/web/20161001165059/http://www.in-pharmatechnologist.com/Regulatory-Safety/GSK-Japan-delays-alopecia-drug-launch-after-Catalent-manufacturing-halt|url-status=live}}</ref> It has not been approved for this indication in the United States,<ref name="ShapiroOtberg2015"/><ref name="pmid27489426">{{cite journal | vauthors = Choi GS, Kim JH, Oh SY, Park JM, Hong JS, Lee YS, Lee WS | title = Safety and Tolerability of the Dual 5-Alpha Reductase Inhibitor Dutasteride in the Treatment of Androgenetic Alopecia | journal = Annals of Dermatology | volume = 28 | issue = 4 | pages = 444–450 | date = August 2016 | pmid = 27489426 | pmc = 4969473 | doi = 10.5021/ad.2016.28.4.444 }}</ref> though it is often used [[off-label]].<ref name="pmid24017975">{{cite journal | vauthors = Nusbaum AG, Rose PT, Nusbaum BP | title = Nonsurgical therapy for hair loss | journal = Facial Plastic Surgery Clinics of North America | volume = 21 | issue = 3 | pages = 335–342 | date = August 2013 | pmid = 24017975 | doi = 10.1016/j.fsc.2013.04.003 }}</ref>

==Society and culture==

[[File:Avodart.jpg|thumb|200px|right|Avodart (dutasteride) 500 μg soft capsules]]

===Generic names===

Dutasteride is the [[Genetic medicine|generic name]] of the drug Avodart and its [[international nonproprietary name]], [[United States Adopted Name]], [[British Approved Name]], and [[Japanese Accepted Name]].<ref name="Drugs.com-2">{{Cite web|url=https://www.drugs.com/international/dutasteride.html|title=Dutasteride|website=Drugs.com|access-date=2017-12-11|archive-date=2017-12-11|archive-url=https://web.archive.org/web/20171211105304/https://www.drugs.com/international/dutasteride.html|url-status=live}}</ref>

===Brand names===

Dutasteride is sold primarily under the brand name Avodart, but also [[dutasteride/tamsulosin|in combination with tamsulosin]] under the brand names Combodart, Duodart, and Jalyn.<ref name="Drugs.com-2" /> Dutasteride is also available in India in combination with [[alfuzosin]] under the brand names Alfusin-D and Dutalfa.<ref name="Drugs.com-2" />

===Availability===

Dutasteride is available widely throughout the world, including in the United States, Canada, the United Kingdom, Ireland, Europe, Australia, South Africa, Latin America, Asia, and elsewhere.<ref name="Drugs.com-2" /> It is available as a generic medication in many countries, including the United States.<ref name="Drugs.com" />

== References ==

{{Reflist}}

== Further reading ==

{{refbegin}}

* {{cite journal | vauthors = Frye SV | title = Discovery and clinical development of dutasteride, a potent dual 5alpha-reductase inhibitor | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 5 | pages = 405–421 | year = 2006 | pmid = 16719800 | doi = 10.2174/156802606776743101 }}

{{refend}}

{{Androgens and antiandrogens}}

{{Drugs used in benign prostatic hypertrophy}}

{{Other dermatological preparations}}

{{GlaxoSmithKline}}

{{Portal bar | Medicine}}

{{Authority control}}

[[Category:5α-Reductase inhibitors]]

[[Category:Androstanes]]

[[Category:Carboxamides]]

[[Category:Diketones]]

[[Category:Hair loss medications]]

[[Category:Hair removal]]

[[Category:Hormonal antineoplastic drugs]]

[[Category:Lactams]]

[[Category:Prostate cancer]]

[[Category:Teratogens]]

[[Category:Trifluoromethyl compounds]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Drugs developed by GSK plc]]