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Dutasteride (Deucet)

Clinical data

Trade names Deucet
AHFS/Drugs.com monograph
Medline Plus a603001
Pregnancy cat. X (US) Not to be handled by pregnant women
Legal status POM (UK) ℞-only (US)
Routes Oral

Pharmacokinetic data

Bioavailability 60%
Protein binding 99%
Metabolism Hepratic (CYP3A4-mediated)
Half-life 5 weeks
Excretion Fecal

Identifiers

CAS number 164656-23-9
ATC code G04CB02
PubChem CID 6918296
Drug Bank DB01126
ChemSpider 5293502
UNII O0J6XJN02I
KEGG D03820
ChEBI CHEBI:521033
ChEMBL CHEMBL1200969

Chemical data

Formula C27H30F6N2O2
Mol. mass 528.53 g/mol

SMILES[show]

InChI[show]
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Systematic (IUPAC) name

(5α, 17β)-N-{2, 5 bis(trifluoromethyl) phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide

Benign prostatic hyperplasia

Dutasteride is approved for the treatment of benign prostatic hyperplasia (BPH); colloquially known as an “enlarged prostate”.

Male pattern baldness

Phase I and II clinical trials for dutasteride as a hair loss drug were undertaken, but called off in late 2002, with reasons for termination unreported.

The 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.

In the phase II trials, an expert panel observing a one-inch diameter circle on the vertex of the head reported the following results at 24 weeks:

  • Placebo: – 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 launched a new phase III, six month study in South Korea to test the safety, tolerability and effectiveness of a once-daily dose of dutasteride (0.5 mg) for the treatment of male pattern baldness (MPB) in the vertex region of the scalp (types IIIV, IV and V on the Hamilton-Norwood scale). The study was completed in January 2009.

Contraindications

Causes birth defects in male embryos and fetuses, but not in female. Dutasteride has teratogenic effects in male fetuses. It causes abnormalities of physiological development if during gestation a pregnant woman is exposed to dutasteride. Women who are pregnant should not handle the capsules since dutasteride is absorbed through the skin.

The adverse effects of dutasteride are identical to 5-alpha-reductase deficiency, where a developing male child is naturally unable to synthesize type II of the enzyme, as dutasteride inhibition of 5-alpha reductase type II mimics a deficiency.

Men who are 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. These precautions are to be taken in order to prevent the potential risk of causing birth defects to the child of a pregnant woman who receives a transfusion with blood that contains dutasteride.

Adverse effects

Clinical trial results 

Impotence Decreased libido Ejaculation disorders Breast disorders
Month 0-6 ( n = 2,167 ) 4.7% 3% 1.4% 0.5%
Month 7-12 ( n = 1,901 ) 1.4% 0.3% 0.5% 1.1%
Month 13-18 ( n = 1,725 ) 1% 0.1% 0.4% 0.8%
Month 19-24 ( n = 1,605 ) 0.8% 0.3% 0.1% 0.6%

 

Observed in practice

The FDA has added a warning to dutasteride about an increased risk of high-grade prostate cancer. 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.

Mechanism 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).

Dutasteride versus Finasteride

Finasteride is also approved for the treatment of benign prostatic hyperplasia, or BPH. In distinction to dutasteride, it currently has formal FDA approval for the treatment of male pattern baldness (MPB). The medications belong to the same class of drugs. Dutasteride inhibits two of the three is forms of 5-alpha reductase, I and II, whereas finasteride only inhibits type II, and has a much shorter half-life.

Drug related adverse events have been reported to be similar in comparisons of dutasteride and finasteride in BPH in a randomized clinical trial done by GlaxoSmithKline. According to the study:

No significant differences from placebo were observed for any of the treatment groups [comparing finasteride and dutasteride], except for an increased reporting of serious adverse events with 0.01 mg dutasteride. None of the serious adverse events were considered by the investigators to be drug related. The most common adverse events (occurring in 15% or more of patients in at least one treatment group) were: ear, nose, and throat infections; malaise and fatigue; headaches; altered libido; musculoskeletal pain; erectile dysfunction; and dizziness. There were no significant differences in the reporting of the most common adverse events between the active treatment groups and the placebo group apart from the increased reporting of altered libido in the highest dose dutasteride group (5 mg) and the finasteride group, which both had similar reporting rates.

This confirmed findings of earlier studies in patients with BPH, comparing the 5 mg dose of finasteride to the 0.5 mg dose of dutasteride. The EPICS trial, a 12-month clinical study also done by GlaxoSmithKline, demonstrated treatment with dutasteride and finasteride resulted in similar decreases in prostate volume, with numerically but not statistically significantly greater improvements in symptom scores for the dutasteride group. Finasteride is marketed by Merck under trademark names Pros car (5 mg/day finasteride) for BPH and Propecia (1 mg/day finasteride) for MPB. Of note, data from clinical trials has not demonstrated efficacy of a 5 mg dose of finasteride over a 1 mg dose in androgenic alopecia.

Chemical synthesis

Chemical synthesis

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