Finasteride
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Finasteride
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| Systematic (IUPAC) name | |
| N-(1,1-dimethylethyl)-3-oxo- (5α,17β)-4-azaandrost-1-ene-17-carboxamide |
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| Identifiers | |
| CAS number | |
| ATC code | G04 D11 |
| PubChem | |
| DrugBank | |
| ChemSpider | |
| 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 | |
| Routes | Oral |
Finasteride (marketed as Proscar, Propecia, Fincar, Finpecia, Finax, Finast, Finara, Finalo, Prosteride, Gefina, Appecia, Finasterid IVAX, Finasterid Alternova) is a synthetic antiandrogen which acts by inhibiting type II 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone (DHT). It is used as a treatment in benign prostatic hyperplasia (BPH) in low doses, and prostate cancer in higher doses. A May, 2008 study indicates that finasteride reduces the rate of prostate cancer by 30% (see below). It is also indicated for use in combination with doxazosin therapy to reduce the risk for symptomatic progression of BPH. Additionally, it is registered in many countries for androgenetic alopecia (male-pattern baldness).
Finasteride was approved initially in 1992 as Proscar, a treatment for prostate enlargement, but the sponsor had studied 1 mg of finasteride and demonstrated hair growth in male pattern hair loss. In 1997, the U.S. Food and Drug Administration approved finasteride to treat male pattern hair loss. Merck sells it under the brand name Propecia.
In December of 2008, the Swedish Medical Products agency concluded a safety investigation of Propecia. The Agency's updated safety information lists difficulty in obtaining an erection that persists even after discontinuing Propecia as a possible side effect.[1]
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Brand names
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.
Generic versions
Merck's patent on finasteride (for the treatment of BPH) expired on June 19, 2006.[2] 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.[3]
Several companies outside the US currently manufacture generic finasteride and sell it at a significantly lower cost than Merck:
- 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)
Side effects
The Swedish Medical Products agency advise that use of Propecia may result in persistent sexual side effects. The Agency lists difficulty in obtaining an erection even after discontinuation of Propecia as a possible side effect.
Recognized side effects, experienced by around >1% of users, include erectile dysfunction, and less often gynecomastia (breast gland enlargement). [2] As expected from its short 6-8 hour half-life, in trial studies, side effects ceased after dosage was discontinued.[specify]
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.[4] Finasteride is known to affect blood donations, and potential donors are typically restricted for at least a month after their most recent dose.[5]
Finasteride has been linked with depression.[6] The drug also caused reductions in allopregnanolone, a potent, endogenous positive modulator of the GABA-A receptor, in very large doses in rodent studies.[7]
Many sports organizations have banned finasteride because it can be used to mask steroid abuse.[8] Since 2005, finasteride has been on the World Anti-Doping Agency's list of banned substances. 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.[9]
Use as a treatment for hair loss
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.[10] 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.[11] In clinical studies, Propecia, like minoxidil, was shown to work on both the crown area and the hairline,[12] 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 generally 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.[citation needed] 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 testosterone. Many doctors prescribe it for women, but not without either careful birth control measures or assurance that the woman cannot become pregnant.
Possible health concerns
The UC Berkeley Wellness Letter expressed concern in March 2003 about the unproven long-term safety of Propecia and recommended cutting a standard 1 milligram dose of Propecia into quarters to reduce the cost without reducing its effectiveness. This claim appears to be supported by clinical pharmacological data reviewed by the FDA during Propecia's approval process that suggested that the advantage of taking 1 mg per day over 0.2 mg per day is statistically small.[13] Some people have unsuccessfully petitioned the FDA to re-examine the approved dosage in light of the statistical evidence and unknown long-term risks.[14] The FDA responded and said that just because the level of DHT found in the scalp was not significantly different does not mean there is a correlation with hair loss. A study would have to show that the benefits of using 0.2 mg and 1 mg were not statistically different. According to the FDA such a study has been performed and a 1 mg dose has a greater benefit whilst remaining equally safe. The same study also concluded that doses of 0.01 mg per day were found to be ineffective in treating hair loss.[14]
The 2005 Prostate Cancer Prevention Trial (PCPT) showed at a dosage of 5 mg per day, as is commonly prescribed for BPH, though much higher than the 1 mg generally prescribed for hair loss, participants taking finasteride were 25% less likely to have developed prostate cancer at the end of the trial compared to those taking a placebo.[15] It appeared (incorrectly) that finasteride increased the specificity and selectivity of prostate cancer detection, thus, a seemly 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. Finasteride did not increase the risk of high-grade prostate cancer.[16][17]
Propecia's effects in detail
DHT is a derivative hormone (metabolite) of testosterone that has been shown to be critical to the initiation and progression of follicular miniaturization and eventual destruction of hair follicles in male pattern baldness. DHT is a steroid hormone just like testosterone but with greater affinity for the androgen receptor. Converting testosterone to DHT thus increases many of its effects.
While the mechanism by which DHT is involved in hair loss is not confirmed, many dermatologists and research scientists specializing in hair loss believe DHT molecules may diffuse into the interior of hair follicle cells (the cytoplasm or cytosol) and bind with androgen receptors. This complex, both the receptor and the DHT molecule, then enters the nucleus of the cell. In the nucleus of the hair follicle cell this complex could then alter the rate of protein synthesis in men who are genetically predisposed to baldness.[citation needed]
However, DHT also plays an important role in the functioning of the central nervous system (the brain), the testicles and prostate, and almost everything but muscle tissue. In muscle tissue testosterone is the dominant hormone, which is why some bodybuilders inject testosterone derivatives to aid in muscular development.
- Propecia (and other products containing finasteride) causes a rise in testosterone levels, because testosterone that would normally be converted into DHT remains testosterone. Continual high levels of testosterone in the body could possibly have negative side effects.[specify]
- Artificially low levels of DHT in the body could cause some unwanted conditions. DHT is an antagonist of estrogen. Men’s bodies also produce the female hormone estrogen in the adrenal glands, although this is just one-tenth of the estrogen that premenopausal women produce in their ovaries. By reducing DHT with drugs, a man’s protection from the effects of estrogen may also be reduced. This could result in gynecomastia.
- Even though both finasteride and dutasteride were developed to combat benign prostatic hyperplasia by reducing DHT in prostate tissue, some scientists question the wisdom of using these 5-alpha reductase inhibitors in younger men who have no problem with their prostates. A research chemist, Patrick Arnold, says “Evidence is mounting that the existence of a high estrogen/androgen ratio – a condition common in older men – is highly correlated with the development of benign prostatic hyperplasia.”[citation needed] However, in apparent contradiction, individuals with 5-alpha-reductase deficiency (and thus a similar hormonal profile to users of DHT inhibitors) do not experience BPH.
Notes and references
- ^ [1]
- ^ Primary Patent Expirations for Selected High Revenue Drugs
- ^ fda.gov - Patent Expiration for Propecia
- ^ Male hair-loss treatment, indication, and safety information at propecia.com
- ^ "FDA guidance on blood donors and medications" (pdf). U.S. Food and Drug Administration. http://www.fda.gov/Cber/bldmem/072893.pdf. Retrieved on 01-02-2009.
- ^ Rahimi-Ardabili B, Pourandarjani R, Habibollahi P, Mualeki A (2006). "Finasteride induced depression: a prospective study". BMC Clin Pharmacol 6: 7. doi:. PMID 17026771.
- ^ Verleye M, Akwa Y, Liere P, et al (Dec 2005). "The anxiolytic etifoxine activates the peripheral benzodiazepine receptor and increases the neurosteroid levels in rat brain". Pharmacol Biochem Behav. 82 (4): 712–20. doi:. PMID 16388839.
- ^ Skin Deep; Fighting Baldness, and Now an Olympic Ban - New York Times
- ^ "Theodore's hair tonic causes positive test". TSN. 2006-02-10. http://tsn.ca/nhl/story/?id=154231. Retrieved on 2006-07-22.
- ^ http://www.propecia.com/finasteride/propecia/consumer/facts/clinical_study.jsp
- ^ Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
- ^ 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.
- ^ "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.
- ^ 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.
- ^ "Can Prostate Cancer Be Prevented?" American Cancer Society, May 25, 2005.
- ^ 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 on 2008-06-15.
- ^ 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:. http://cancerpreventionresearch.aacrjournals.org/cgi/rapidpdf/1940-6207.CAPR-08-0092v1.
See also
External links
- Propecia Manufacturer's website
- Proscar Manufacturer's website
- Propecia Research Latest studies
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