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| Routes of administration | Oral |
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| Bioavailability | 63% |
| Metabolism | Hepatic |
| Elimination half-life | Elderly: 8 hours Adults: 6 hours |
| Excretion | Feces (57%) and urine (39%) as metabolites |
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| ECHA InfoCard | 100.149.445  |
| Chemical and physical data | |
| Formula | C23H36N2O2 |
| Molar mass | 372.549 g/mol g·mol |
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Finasteride (marketed by Merck under the trademark names Proscar and Propecia, also available under several generic names) is a synthetic antiandrogen that inhibits 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, as treatment for benign prostatic hyperplasia (BPH). In 1997, the FDA approved finasteride to treat male pattern baldness (MPB) under the brand name Propecia.
Uses
Finasteride is used in the treatment of benign prostatic hyperplasia (BPH), and male pattern baldness (MPB).
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.
Hair loss
In a 5-year study of men with mild to moderate hair loss, 2 out of 3 of the men who took Propecia (finasteride 1 mg) daily regrew some hair, as measured by hair counts. In contrast, all of the men in the study who were not taking finasteride lost hair. In the same study, based on photographs that were reviewed by an independent panel of dermatologists, 48% of those treated with Propecia experienced visible 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. 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. In clinical studies, Propecia, like minoxidil, was shown to work on both the crown area and the hairline, but is most successful in the crown area.
Some users, in an effort to save money, buy Proscar (finasteride 5 mg) instead of Propecia, and split the Proscar pills into several parts to approximate the Propecia dosage. The pills are coated to prevent contact with the active ingredient during handling, and the dust or crumbs from broken Proscar tablets should be kept away from pregnant women or women who may become pregnant.
Propecia has been shown to be ineffective for treating hair loss in women. 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 use of finasteride to prevent prostate cancer is controversial. Some urologists believe it can prevent prostate cancer, while others believe that it merely shrinks low-grade tumors that would not be lethal, and may even delay detection of cancers until they become high-grade and are difficult to treat.
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. 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.
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 men who continued therapy.
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.
The UK's Medical and Healthcare Products Regulatory Agency (MHRA) say that erectile dysfunction that persists once use of Propecia has stopped has been reported to them.
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.
Finasteride is known to affect blood donations, and potential donors are typically restricted for at least a month after their most recent dose.
Many sports organizations have banned finasteride because it can be used to mask steroid abuse. 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. 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.
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 5 mg 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.
Mechanism of action
Testosterone in males is produced primarily in the testicles, but also in the adrenal glands. The majority of testosterone in the body is bound to sex hormone-binding globulin (SHBG), a protein produced in the liver that transports testosterone in the bloodstream, prevents its metabolism, and prolongs its half-life. Once it becomes unbound from SHBG, free testosterone can enter cells throughout the body. In certain tissues, the most notable ones being the scalp, skin, and prostate, testosterone is converted into dihydrotestosterone (DHT) by the enzyme 5-alpha reductase. DHT is a more powerful androgen than testosterone (as it has a much higher affinity for the androgen receptor), so, by converting testosterone to DHT, 5-alpha reductase, in essence, amplifies the androgenic effect of testosterone in the tissues in which it is found.
Finasteride is an inhibitor of 5-alpha reductase. By blocking this enzyme, finasteride blocks the conversion of testosterone into the more powerful androgen DHT. This reduces androgenic activity in the scalp, treating hair loss at its hormonal source. In the prostate, inhibition of 5-alpha reductase leads to a reduction of prostate volume, which improves the symptoms of benign prostatic hyperplasia (BPH) and reduces the risk of prostate cancer.
Preparations
Drug trade names include Propecia and Proscar, the former marketed for male pattern baldness (MPB) and the latter for benign prostatic hyperplasia (BPH), both are products of Merck & Co. 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. Merck was awarded a separate patent for the use of finasteride to treat MPB. This patent is set to expire in November 2013.
Some studies have shown that the dose of finasteride needed to treat male pattern baldness may be smaller than 1 mg. Petitions to the FDA to re-examine the approved dosage in light of the statistical evidence and possible long-term risks, 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.
Chemistry
- Rasmusson, Gary H.; Reynolds, Glenn F.; Steinberg, Nathan G.; Walton, Edward; Patel, Gool F.; Liang, Tehming; Cascieri, Margaret A.; Cheung, Anne H.; Brooks, Jerry R. (1986). "Azasteroids: structure-activity relationships for inhibition of 5.alpha.-reductase and of androgen receptor binding". Journal of Medicinal Chemistry. 29 (11): 2298. doi:10.1021/jm00161a028. PMID 3783591.
- Bhattacharya, Apurba.; Dimichele, Lisa M.; Dolling, Ulf H.; Douglas, Alan W.; Grabowski, Edward J. J. (1988). "Silylation-mediated oxidation of 4-aza-3-ketosteroids with DDQ proceeds via DDQ-substrate adducts". Journal of the American Chemical Society. 110: 3318. doi:10.1021/ja00218a062.
See also
- Dutasteride
- Dihydrotestosterone
- Male pattern baldness
- Management of baldness
- Benign prostatic hyperplasia
References
- Edwards JE, Moore RA (2002). "Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials". BMC Urol. 2: 14. doi:10.1186/1471-2490-2-14. PMC 140032. PMID 12477383.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: unflagged free DOI (link) - Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
- Leyden J, Dunlap F, Miller B; et al. (1999). "Finasteride in the treatment of men with frontal male pattern hair loss". J. Am. Acad. Dermatol. 40 (6 Pt 1): 930–7. doi:10.1016/S0190-9622(99)70081-2. PMID 10365924.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - Morrow, David J. (March 19, 1999). "New Profits in Old Bottles; Companies Find Bonus in Drugs That Cure Several Ills". The New York Times. Retrieved June 6, 2010.
{{cite news}}: Italic or bold markup not allowed in:|publisher=(help) - "Patient Information About Proscar" (PDF). Merck Sharp & Dohme Corp.
- The Drug Propecia and Hair Loss | HealthGuidance
- Walsh PC (2010). "Chemoprevention of prostate cancer". N. Engl. J. Med. 362 (13): 1237–8. doi:10.1056/NEJMe1001045. PMID 20357287.
{{cite journal}}: Unknown parameter|month=ignored (help) - "Can Prostate Cancer Be Prevented?" American Cancer Society, May 25, 2005.
- Gina Kolata (June 15, 2008). "New Take on a Prostate Drug, and a New Debate". NY Times. Retrieved 2008-06-15.
- Potosky A, Miller B, Albertsen P, Kramer B (2008). "Finasteride Does Not Increase the Risk of High-Grade Prostate Cancer: A Bias-Adjusted Modeling Approach". Cancer Prevention Research. 1 (3): 174–81. doi:10.1158/1940-6207.CAPR-08-0092. PMC 2844801. PMID 19138953.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - Drugs.com | Propecia Side Effects
- Package Leaflet Information for the User, Swedish package insert for Propecia 1mg
- MHRA PUBLIC ASSESSMENT REPORT | The risk of male breast cancer with finasteride
- "FDA guidance on blood donors and medications" (PDF). U.S. Food and Drug Administration. Archived from the original (pdf) on October 31, 2005. Retrieved 01-02-2009.
{{cite web}}: Check date values in:|accessdate=(help) - Sandomir, Richard (2006-01-19). "Skin Deep; Fighting Baldness, and Now an Olympic Ban". The New York Times. Retrieved 2010-05-02.
- World Anti-Doping Agency Q&A: Status of Finasteride
- "Theodore's hair tonic causes positive test". TSN. 2006-02-10. Retrieved 2006-07-22.
- "MHRA drug safety advice: Finasteride and potential risk of male breast cancer". 4 December 2009. Retrieved 4 December 2009.
- Primary Patent Expirations for Selected High Revenue Drugs
- fda.gov | Patent Expiration for Propecia
- "Center for Drug Evaluation and Research, Application Number NDA 20-788" (PDF). U.S. Food and Drug Administration.
- ^ "Letter to Dr. Sherman Frankel, University of Pennsylvania" (PDF). U.S. Food and Drug Administration.
External links
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| Drugs used in benign prostatic hyperplasia (G04C) | |
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| 5α-Reductase inhibitors | |
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