Dutasteride

Dutasteride

Systematic (IUPAC) name
(5α, 17β)-N-{2,5-Bis(trifluoromethyl)phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide
Clinical data
Trade names	Avodart
AHFS/Drugs.com	monograph
MedlinePlus	a603001
Pregnancy category	US: X (Contraindicated) Not to be handled by pregnant women
Routes of administration	Oral
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	60%
Protein binding	99%
Metabolism	Hepatic (CYP3A4-mediated)
Biological half-life	5 weeks
Excretion	Fecal
Identifiers
CAS Number	164656-23-9
ATC code	G04CB02 (WHO)
PubChem	CID 6918296
IUPHAR/BPS	7457
DrugBank	DB01126
ChemSpider	5293502
UNII	O0J6XJN02I
KEGG	D03820
ChEBI	CHEBI:521033
ChEMBL	CHEMBL1200969
Synonyms	GG-745, GI-198745
Chemical data
Formula	C27H30F6N2O2
Molar mass	528.53 g/mol
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
InChI InChI=1S/C27H30F6N2O2/c1-24-11-9-17-15(4-8-21-25(17,2)12-10-22(36)35-21)16(24)6-7-19(24)23(37)34-20-13-14(26(28,29)30)3-5-18(20)27(31,32)33/h3,5,10,12-13,15-17,19,21H,4,6-9,11H2,1-2H3,(H,34,37)(H,35,36)/t15-,16-,17-,19+,21+,24-,25+/m0/s1 Key:JWJOTENAMICLJG-QWBYCMEYSA-N
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Dutasteride (INN, USAN, BAN, JAN) (brand name Avodart), manufactured by GlaxoSmithKline, is a triple 5α-reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone (DHT).^[1] It is used to treat benign prostatic hyperplasia. It increases the risk of erectile dysfunction^[2] and decreased sexual desire.^[3]

Medical uses

Avodart (dutasteride) 500 µg soft capsules

Dutasteride is useful for treating benign prostatic hyperplasia (BPH); colloquially known as an "enlarged prostate".^[4]

In those who are being regularly screened, 5α-reductase inhibitors such as finasteride and dutasteride reduce the overall risk of being diagnosed with prostate cancer; however, there is insufficient data to determine if they have an effect on the risk of death and may increase the chance of more serious cases.^[5]

Adverse effects

Sexual effects

This class of medications increases rates of erectile dysfunction (with between 5% and 9% developing problems after starting their use).^[2] This is linked to lower quality of life and can cause stress in relationships.^[2] There is also an association with lowered sexual desire.^[3] It has been reported that these adverse sexual side effects may persist even after discontinuation of the drug.^[3]

Prostate cancer

The FDA has added a warning to dutasteride about an increased risk of high-grade prostate cancer.^[6] While the potential for positive, negative or neutral changes to the potential risk of developing prostate cancer with dutasteride has not been established, evidence has suggested it may temporarily reduce the growth and prevalence of benign prostate tumors, but could also mask the early detection of prostate cancer. The primary area for concern is for patients who may develop prostate cancer whilst taking dutasteride for benign prostatic hyperplasia, which in turn could delay diagnosis and early treatment of the prostate cancer, thereby potentially increasing the risk of these patients developing high-grade prostate cancer.^[7]

Contraindications

Children and women who are or may become pregnant, and people with known significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride or finasteride should not take dutasteride. Exposure to dutasteride and other 5α-reductase inhibitors during pregnancy can cause birth defects. Since these medications are readily absorbed through the skin, women who are or may become pregnant should not handle them and if they come into contact with leaking capsules, the contact area should be washed immediately in soapy water. People taking dutasteride should not donate blood and, due to its long half-life, should also not donate blood for at least 6 months after the cessation of treatment.^[8]

Mechanism of action

Dutasteride belongs to a class of drugs called 5α-reductase inhibitors, which block the action of the 5α-reductase enzymes that convert testosterone into dihydrotestosterone (DHT).

Dutasteride versus finasteride

Finasteride is also approved for the treatment of benign prostatic hyperplasia, or BPH. The medications belong to the same class of drugs.

Dutasteride inhibits all three isoforms of 5α-reductase, types I, II, and III, whereas finasteride only inhibits types II and III,^[1] and has a much shorter half-life.

Society and culture

FDA approval

Dutasteride is approved by the Food and Drug Administration (FDA) for treatment of benign prostatic hyperplasia.

See also

• Alfatradiol
• Antineurosteroid
• Saw palmetto extract

References

1. Yamana K, Labrie F, Luu-The V (January 2010). "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". Hormone Molecular Biology and Clinical Investigation 2 (3). doi:10.1515/hmbci.2010.035.
2. Gur, S; Kadowitz, PJ; Hellstrom, WJ (January 2013). "Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation.". Expert opinion on drug safety 12 (1): 81–90. doi:10.1517/14740338.2013.742885. PMID 23173718.
3. Traish, AM; Hassani, J; Guay, AT; Zitzmann, M; Hansen, ML (March 2011). "Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients.". The journal of sexual medicine 8 (3): 872–84. doi:10.1111/j.1743-6109.2010.02157.x. PMID 21176115.
4. Slater, S; Dumas, C; Bubley, G (March 2012). "Dutasteride for the treatment of prostate-related conditions.". Expert opinion on drug safety 11 (2): 325–30. doi:10.1517/14740338.2012.658040. PMID 22316171.
5. Wilt TJ, MacDonald R, Hagerty K, Schellhammer P, Kramer BS (2008). "Five-alpha-reductase Inhibitors for prostate cancer prevention". Cochrane Database Syst Rev (2): CD007091. doi:10.1002/14651858.CD007091. PMID 18425978.
6. 5-alpha reductase inhibitors (5-ARIs): Label Change - Increased Risk of Prostate Cancer | U.S. Department of Health & Human Services
7. Walsh, PC (Apr 1, 2010). "Chemoprevention of prostate cancer.". The New England Journal of Medicine 362 (13): 1237–8. doi:10.1056/NEJMe1001045. PMID 20357287.
8. "FDA prescribing information" (PDF). June 2011. Retrieved 15 September 2013.

External links

• Avodart full prescribing information
• Frye, S. (2006). "Discovery and Clinical Development of Dutasteride, a Potent Dual 5α- Reductase Inhibitor". Current Topics in Medicinal Chemistry 6 (5): 405–21. doi:10.2174/156802606776743101. PMID 16719800.