Dutasteride
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| 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 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 | Hepatic (CYP3A4-mediated) |
| Half-life | 5 weeks |
| Excretion | Fecal |
| Identifiers | |
| CAS number | 164656-23-9  |
| ATC code | G04CB02 |
| PubChem | CID 6918296 |
| DrugBank | APRD00385 |
| ChemSpider | 5293502 |
| UNII | O0J6XJN02I |
| KEGG | D03820 |
| ChEBI | CHEBI:521033 |
| ChEMBL | CHEMBL1200969  |
| Chemical data | |
| Formula | C27H30F6N2O2 |
| Mol. mass | 528.53 g/mol |
| SMILES | eMolecules & PubChem |
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Dutasteride (trade name Avodart by GlaxoSmithKline) is a dual 5-a reductase inhibitor that inhibits conversion of testosterone to dihydrotestosterone (DHT).
Dutasteride is approved for treatment of benign prostatic hyperplasia (BPH) and is also prescribed off-label for treatment of male pattern baldness (MPB).
Contents |
[edit] Medical uses
[edit] Benign prostatic hyperplasia
Dutasteride is approved for the treatment of benign prostatic hyperplasia (BPH) (also known as enlarged prostate).
[edit] 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 unknown.
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.[1]
Phase II study 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 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.[2][3] Future intentions by GlaxoSmithKline to continue or abandon plans for FDA approval of dutasteride in treatment of MPB remain unknown.
[edit] 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 dusteride are identical 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 inactivates 5-alpha reductase type II developing males would have the same adverse effects as a result of the drug as they would have with the 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 in a pregnant woman who receives a transfusion with blood that contains dutasteride.[4]
[edit] Adverse effects
[edit] Clinical trial results
Month 0-6 ( n = 2,167 ) [5]
- Impotence: 4.7%
- Decreased libido: 3%
- Ejaculation disorders: 1.4%
- Breast disorders: 0.5%
Month 7-12 ( n = 1,901 ) [5]
- Impotence: 1.4%
- Decreased libido: 0.3%
- Ejaculation disorders: 0.5%
- Breast disorders: 1.1%
Month 13-18 ( n = 1,725 ) [5]
- Impotence: 1%
- Decreased libido: 0.1%
- Ejaculation disorders: 0.4%
- Breast disorders: 0.8%
Month 19-24 ( n = 1,605 ) [5]
- Impotence: 0.8%
- Decreased libido: 0.3%
- Ejaculation disorders: 0.1%
- Breast disorders: 0.6%
[edit] Observed in practice
The FDA has added warning to dutasteride about an increased risk of high-grade prostate cancer.[6] Whilst 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]
[edit] Development
[edit] 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). Finasteride, which is also approved for the treatment of benign prostatic hyperplasia (BPH), in addition to the treatment of male pattern baldness (MPB), belongs to this class of drugs. Dutasteride inhibits both isoforms of 5-alpha reductase, type I and type II, whereas finasteride only inhibits type II. There are no long-term randomized trials comparing the effects of dutasteride and finasteride in patients with BPH. The EPICS trial, a 12-month clinical study 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.[8] Finasteride is marketed by Merck under trademark names Proscar (5 mg/day finasteride) for BPH and Propecia (1 mg/day finasteride) for MPB. Published data from controlled clinical trials demonstrated the 5 mg dose of finasteride did not produce better results than the 1 mg dose.[9]
[edit] Chemical synthesis
Batchelor, K. W.; Frye, S. V.; Dorsey, G. F.; Mook, R. A.; 1996, U.S. Patent 5,565,467.
[edit] See also
- Finasteride, related 5-alpha reductase inhibitor.
[edit] References
- ^ 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.
- ^ ClinicalTrials.gov NCT00441116
- ^ Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: A randomized, double-blind, placebo-controlled, phase III study | Journal of the American Academy of Dermatology (JAAD)
- ^ Avodart Information | Drugs.com
- ^ a b c d Avodart Side Effects | Drugs.com
- ^ 5-alpha reductase inhibitors (5-ARIs): Label Change - Increased Risk of Prostate Cancer | U.S. Department of Health & Human Services
- ^ Walsh, PC (2010 Apr 1). "Chemoprevention of prostate cancer.". The New England journal of medicine 362 (13): 1237–8. doi:10.1056/NEJMe1001045. PMID 20357287.
- ^ Managing the progression of lower urinary tract symptoms/benign prostatic hyperplasia: therapeutic options for the man at risk | UroToday
- ^ Propecia (Finasteride) - See "Increasing the Dose" | Bernstein Medical Center for Hair Restoration
[edit] External links
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