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Dutasteride
Systematic (IUPAC) name
(5α, 17β)-N-{2,5 bis(trifluoromethyl) phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide
Identifiers
CAS number 164656-23-9
ATC code G04CB02
PubChem 6918296
DrugBank APRD00385
ChemSpider 5293502
Chemical data
Formula C27H30F6N2O2 
Mol. mass 528.53 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 60%
Protein binding 99%
Metabolism Hepatic (CYP3A4-mediated)
Half life 5 weeks
Excretion Fecal
Therapeutic considerations
Pregnancy cat. X(US) Not to be handled by pregnant women
Legal status POM (UK) -only (US)
Routes Oral
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Dutasteride (marketed as Avodart, Avidart, Avolve, Duagen, Dutas, Dutagen, Duprost) is a 5-alpha-reductase inhibitor that inhibits the conversion of testosterone into dihydrotestosterone (DHT). It is approved for the treatment of benign prostatic hyperplasia (BPH) and is prescibed off-label for the treatment of male pattern baldness (MPB). Avodart is manufactured and marketed by GlaxoSmithKline.

Contents

Classification and method of action

Dutasteride belongs to a class of drugs called 5-alpha-reductase inhibitors, which block the action of the 5-alpha-reductase enzymes that convert testosterone into dihydrotestosterone (DHT). Finasteride, which is also approved for BPH, but also the treatment of hair loss, belongs to this group of drugs. Dutasteride inhibits both isoforms of 5-alpha reductase, Type I and Type II, while finasteride only inhibits Type II. A clinical study done by GlaxoSmithKline, the EPICS trial, did not find dutasteride to be more effective than finasteride in treating BPH.

Uses

While dutasteride is only officially approved to treat enlargement of the prostate gland (at a dose of 0.5 mg/day),[1] phase I and II clinical trials for dutasteride as a hair loss drug were also undertaken, but called off in late 2002. The reason the trials were called off is not publicly known. Industry sources speculate that Avodart would have been seen as too similar to Propecia to have proved profitable as a hair loss treatment. However, phase II results indicated that dutasteride at both 0.5 mg and 2.5 mg/day generated a superior hair count to finasteride 5 mg at 12 and 24 weeks.[2]

In this phase II, dose-ranging study, 2.5 mg dutasteride was superior to 5 mg finasteride in improving scalp hair growth in men between ages 21 and 45 years with MPB as judged by target area hair counts, expert panel assessment, and investigator assessment at 12 and 24 weeks.

In a test area at 24 weeks, results showed:[3]

Placebo - Minus 32.3 hairs

Finasteride 5 mg - 75.6 hairs

Dutasteride 0.1 mg - 78.5 hairs

Dutasteride 0.5 mg - 94.6 hairs

Dutasteride 2.5 mg - 109.6 hairs

In December 2006, GlaxoSmithKline started a new Phase III, six month study in Korea to test the safety, tolerability and effectiveness of a once-daily dose of dutasteride (0.5 mg) for the treatment of MPB in the vertex region of the scalp (types IIIv, IV and V on the Hamilton-Norwood scale). The study has been completed as of January 2009.[4] The future impact that this study will have on the approval or disapproval by the U.S. Food and Drug Administration (FDA) of Avodart for the treatment of MPB in the United States is yet to be determined.

Dutasteride is also in development for prostate cancer risk reduction.[5]

The results of the REDUCE trial were presented at the American Urologic Association meeting in 2009 which demonstrated that higher risk patients for prostate cancer with a PSA value of 2.5 to 10 and a prior negative prostate biopsy demonstrated a 23% reduction in the incidence of prostate cancer over a four year period in this population with daily 0.5 mg dutasteride dosage.

Side effects

Avodart 500 micrograms soft capsules (AU)

Adverse events[6]

Year 1

Placebo (n = 2158)

Impotence 3% - Decreased libido 2% - Ejaculation disorders <1% - Breast Disorders <1%

Avodart (n = 2167)

Impotence 6% - Decreased libido 4% - Ejaculation disorders 2% - Breast Disorders 1%

Year 2

Placebo (n = 1736 )

Impotence 1% - Decreased libido <1% - Ejaculation disorders <1% - Breast Disorders <1%

Avodart (n = 1744)

Impotence 2% - Decreased libido <1% - Ejaculation disorders <1% - Breast Disorders 1%

Teratogenic effect

The teratogenic effect from dutasteride is harmful to male children. Women who are pregnant should not handle the capsules, as inadvertent consumption could cause birth defects of the male fetus. The effect would be similar to 5-alpha-reductase deficiency, where a developing male child is naturally deficient in 5-alpha reductase Type II, and thus unable to synthesize it. As dutasteride blocks the same process, developing males would have a DHT deficiency with its adverse effects as a result of the drug.

Men should not donate blood while taking Avodart and for at least 6 months after treatment ends. Avodart can be carried in the blood and could cause birth defects if a pregnant women receives a transfusion with blood that contains dutasteride.[7]

See also

External links

References

  1. ^ Avodart 0.5mg soft capsules, SPC from the eMC
  2. ^ Olsen EA, Hordinsky M, Whiting D, et al. (Dec 2006). "The importance of dual 5alpha-reductase inhibition in the treatment of MPB: results of a randomized placebo-controlled study of dutasteride versus finasteride". J Am Acad Dermatol. 55 (6): 1014–23. doi:10.1016/j.jaad.2006.05.007. PMID 17110217. 
  3. ^ Dutasteride vs. Finasteride - Bernstein Medical Center for Hair Restoration
  4. ^ ClinicalTrials.gov NCT00441116
  5. ^ Sound bites for NCE Entries into Phase III
  6. ^ PRODUCT INFORMATION - AVODART® SOFT CAPSULES
  7. ^ Avodart Information from Drugs.com







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