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Finasteride
Systematic (IUPAC) name
N-(1,1-dimethylethyl)-3-oxo-
(5α,17β)-4-azaandrost-1-ene-17-carboxamide
Identifiers
CAS number 98319-26-7
ATC code G04CB01 D11AX10
PubChem 194453
DrugBank APRD00632
ChemSpider 51714
Chemical data
Formula C23H36N2O2 
Mol. mass 372.549 g/mol
Pharmacokinetic data
Bioavailability 63%
Metabolism Hepatic
Half life Elderly: 8 hours
Adults: 6 hours
Excretion Feces (57%) and urine (39%) as metabolites
Therapeutic considerations
Pregnancy cat. X (will cause birth defects in an unborn baby)
Legal status POM (UK) -only (US)
Routes Oral
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Finasteride (marketed as Proscar, Propecia, Fincar, Finpecia, Finax, Finast, Finara, Finalo, Prosteride, Gefina, Appecia, Finasterid IVAX, Finasterid Alternova, Hyplafin, Penester, Finpros, Tectum, Prezepa) is a synthetic antiandrogen that acts by inhibiting type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT). Finasteride was initially approved by the U.S. Food and Drug Administration (FDA) in 1992 under the brand name Proscar, a treatment for benign prostatic hyperplasia (BPH). In 1997, the FDA approved finasteride to treat male pattern baldness (MPB), under the brand name Propecia.

Contents

Uses

Finasteride is used in the treatment of prostate cancer, benign prostatic hyperplasia, and androgenetic alopecia (male pattern baldness).

Benign prostatic hyperplasia

Finasteride is used for the treatment of benign prostatic hyperplasia (BPH) (also known as enlarged prostate) at a dose of 5 mg once a day. It may take six months or more to see the full effects of finasteride. If the drug is discontinued, any therapeutic benefits will be reversed. Finasteride may improve the symptoms associated with BPH such as difficulty urinating, getting up during the night to urinate, hesitation at the start of urination, and decreased urinary flow.[1]

Hair loss

Propecia 1 mg tablets (AU)

In a 5-year study of men with mild to moderate hair loss, 48% of those treated with Propecia (finasteride 1 mg) experienced some regrowth of hair, and a further 42% had no further loss. Average hair count in the treatment group remained above baseline, and showed an increasing difference from hair count in the placebo group, for all five years of the study.[2] Propecia is effective only for as long as it is taken; the hair gained or maintained is lost within 6–12 months of ceasing therapy.[3] In clinical studies, Propecia, like minoxidil, was shown to work on both the crown area and the hairline,[4] but is most successful in the crown area.

Some users, in an effort to save money, buy Proscar instead of Propecia, and split the Proscar pills to approximate the Propecia dosage. Doing so is considered unadvisable if women of pregnancy age are in the household; this is because finasteride, even in small concentrations, can cause birth defects in a developing male fetus. The birth defects involve the development of male genitalia (no such effects have been noted in developing female fetuses). On most product inserts, it will be mentioned that the dust or crumbs from broken Proscar tablets should be kept away from pregnant women.

Propecia has been shown to be ineffective for treating hair loss in women.[5] However, Propecia's supporters respond that the study was on post-menopausal women whose hair loss was more likely related to the loss of estrogen versus a sensitivity to DHT. Doctors may prescribe it for women, but not without sufficient birth control measures in place or assurance that the woman cannot become pregnant.

Prostate cancer

The 2005 Prostate Cancer Prevention Trial (PCPT) showed at a dosage of 5 mg per day, as is commonly prescribed for BPH, participants taking finasteride were 25% less likely to have developed prostate cancer at the end of the trial compared to those taking a placebo.[6] It appeared (incorrectly) that finasteride increased the specificity and selectivity of prostate cancer detection, thus creating an apparently increased rate of high Gleason grade tumor. A 2008 update of this study found that finasteride reduces the incidence of prostate cancer by 30%. In the original study, it turns out that the smaller prostate caused by finasteride means that a doctor is more likely to hit upon cancer nests and more likely to find aggressive-looking cells. Most of the men in the study who had cancer — aggressive or not — chose to be treated, and many had their prostates removed. A pathologist then carefully examined each of those 500 prostates and compared the kinds of cancers found at surgery to those initially diagnosed at biopsy. This study concluded that Finasteride did not increase the risk of high-grade prostate cancer.[7][8]

Side effects

Side effects of finasteride include impotence (1.1% to 18.5%), abnormal ejaculation (7.2%), decreased ejaculatory volume (0.9% to 2.8%), abnormal sexual function (2.5%), gynecomastia (2.2%), erectile dysfunction (1.3%), ejaculation disorder (1.2%) and testicular pain. Resolution occurred in men who discontinued therapy with finasteride due to these side effects and in most of those who continued therapy.[9]

In December 2008, the Swedish Medical Products agency concluded a safety investigation of Propecia and subsequently advised that the use of Propecia may result in irreversible sexual dysfunction. The Agency's updated safety information lists difficulty in obtaining an erection that persists indefinitely, even after the discontinuation of Propecia, as a possible side effect of the drug.[10]

The UK's Medical and Healthcare Products Regulatory Agency (MHRA) say that erectile dysfuction that persists once use of Propecia has stopped has been reported to them. [11]

Finasteride is not indicated for use by women. Finasteride is in the FDA pregnancy category X. This means that it is known to cause birth defects in an unborn baby. Women who are or who may become pregnant must not handle crushed or broken finasteride tablets, because the medication could be absorbed through the skin. Finasteride is known to cause birth defects in a developing male baby. Exposure to whole tablets should be avoided whenever possible, however exposure to whole tablets is not expected to be harmful as long as the tablets are not swallowed.

It is not known whether finasteride passes into breast milk, and thus should not be taken by breastfeeding women. Finasteride may pass into the semen of men, but Merck states that a pregnant woman's contact with the semen of a man taking finasteride is not an issue for concern.[12] Finasteride is known to affect blood donations, and potential donors are typically restricted for at least a month after their most recent dose.[13]

Many sports organizations have banned finasteride because it can be used to mask steroid abuse.[14] Since 2005, finasteride has been on the World Anti-Doping Agency's list of banned substances. However, it was removed from the list in 2009.[15] Notable athletes who used finasteride for hair loss and were banned from international competition include skeleton racer Zach Lund, bobsledder Sebastien Gattuso, footballer Romário and ice hockey goaltender José Théodore.[16]

In December 2009, the Medicines and Healthcare products Regulatory Agency in the UK announced new drug safety advice on finasteride and the potential risk of male breast cancer. The agency concluded that, although overall incidence of male breast cancer in clinical trials for finasteride 5mg was not significantly increased, a higher risk of male breast cancer with finasteride use cannot be excluded. A warning on this risk will be included in the product information.[17]

Mechanism of action

Testosterone is produced in the testicles and the adrenal glands and carried in the bloodstream by sex hormone-binding globulin, a protein produced in the liver, which delivers it to the tissues. Inside the cells, testosterone is converted into dihydrotestosterone (DHT), which is required for its functioning because DHT has a much higher affinity to the androgen receptor, an intracellular receptor which mediates the effect of the hormones on numerous functions. The conversion of testosterone to DHT is done by two isoforms of the enzyme 5-alpha reductase.

In the prostate, inhibition of 5-alpha reductase leads to a reduction of prostate volume and hence improves the symptoms of benign prostatic hyperplasia and reduces the risk of prostate cancer. In hair follicles, DHT is needed for the initiation and progression of follicular miniaturization and eventual destruction of hair follicles in male pattern baldness.

Preparations

Drug trade names include Propecia and Proscar, both products of Merck & Co. (the former is marketed for hair loss in male pattern baldness, and the latter for BPH). There is 1 mg of finasteride in Propecia and 5 mg in Proscar. Merck's patent on finasteride (for the treatment of BPH) expired on June 19, 2006.[18] Merck was awarded a separate patent for the use of finasteride to treat male pattern baldness. This patent is set to expire in November 2013.[19] Some studies have shown that the dose of finasteride needed to treat male pattern baldness may be smaller than 1 mg.[20] Petitions to the FDA to re-examine the approved dosage in light of the statistical evidence and possible long-term risks,[21] were met with the response that a study had shown increased effect of a 1 mg dose compared to 0.2 mg without added risks; the same study also concluded that doses of 0.01 mg per day were found to be ineffective in treating hair loss.[21]

Several companies outside the US currently manufacture generic finasteride:

  • Ajanta Pharma (trade name Appecia)
  • Aleppo Pharmaceutical (trade name Prosteride)
  • Cipla (trade names Fincar and Finpecia)
  • Dr. Reddy's (trade names Finax and Finast),
  • Intas Pharmaceuticals (trade name Finalo)
  • Ranbaxy (trade name Finara)
  • Zentiva (trade name Penester)
  • Actavis (trade name Hyplafin)
  • Zentiva (trade name Finpros)
  • Hemofarm (trade name Tectum)
  • Teva (trade name Prezepa)

Chemistry

Finasteride Synth.png

See also

References

  1. ^ Drugs Factsheet (Proscar) - C-Health
  2. ^ Selected Safety Information About PROPECIA - MERCK
  3. ^ Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
  4. ^ Layden J, Dunlap F, Miller B, Winters P, Lebwohl M, Hecker D, et al. (in press). "Finasteride in the treatment of men with frontal male pattern hair loss". J Am Acad Dermatol. 
  5. ^ The Drug Propecia and Hair Loss - HealthGuidance
  6. ^ "Can Prostate Cancer Be Prevented?" American Cancer Society, May 25, 2005.
  7. ^ Gine Kolata (June 15, 2008). "New Take on a Prostate Drug, and a New Debate". NY Times. http://www.nytimes.com/2008/06/15/health/15prostate.html?ei=5087&em=&en=813eaa4e10f57756&ex=1213675200&adxnnl=1&adxnnlx=1213503418-GD4DbGjYsDxqV/xuGWnE1A. Retrieved 2008-06-15. 
  8. ^ Potosky A, Miller B, Albertsen P, Kramer B (Aug 2008). "Finasteride Does Not Increase the Risk of High-Grade Prostate Cancer: A Bias-Adjusted Modeling Approach". Cancer Prevention Research 1: 174–81. doi:10.1158/1940-6207.CAPR-08-0092. http://cancerpreventionresearch.aacrjournals.org/cgi/rapidpdf/1940-6207.CAPR-08-0092v1. 
  9. ^ Propecia Side Effects - Drugs.com
  10. ^ Package Leaflet Information for the User, Swedish package insert for Propecia 1mg
  11. ^ [1]
  12. ^ Male hair-loss treatment, indication, and safety information at propecia.com
  13. ^ "FDA guidance on blood donors and medications" (pdf). U.S. Food and Drug Administration. http://www.fda.gov/Cber/bldmem/072893.pdf. Retrieved 01-02-2009. 
  14. ^ Skin Deep; Fighting Baldness, and Now an Olympic Ban - New York Times
  15. ^ World Anti-Doping Agency Q&A: Status of Finasteride
  16. ^ "Theodore's hair tonic causes positive test". TSN. 2006-02-10. http://tsn.ca/nhl/story/?id=154231. Retrieved 2006-07-22. 
  17. ^ "MHRA drug safety advice: Finasteride and potential risk of male breast cancer". 04 December 2009. http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Patient-Safety/MHRA-drug-safety-advice-Finasteride-and-potential-risk-of-male-breast-cancer/. Retrieved 04 December 2009. 
  18. ^ Primary Patent Expirations for Selected High Revenue Drugs
  19. ^ fda.gov - Patent Expiration for Propecia
  20. ^ "Center for Drug Evaluation and Research, Application Number NDA 20-788" (PDF). U.S. Food and Drug Administration. http://www.fda.gov/cder/foi/nda/97/20788_PROPECIA%20TABLETS,%201MG_BIOPHARMR.PDF. 
  21. ^ a b "Letter to Dr. Sherman Frankel, University of Pennsylvania" (PDF). U.S. Food and Drug Administration. http://www.fda.gov/ohrms/dockets/dailys/00/Dec00/121800/pav0001.pdf. 

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