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 | 98319-26-7 |
| ATC code | G04CB01 |
| PubChem | 194453 |
| DrugBank | APRD00632 |
| Chemical data | |
| Formula | C23H36N2O2 |
| Mol. weight | 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, Prosteride) is an antiandrogen which acts by inhibiting 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone. It is used in benign prostatic hyperplasia (BPH) in low doses, and in prostate cancer in higher doses. 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 male-pattern baldness.
 Propecia Finasteride |
 Proscar Finasteride |
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 December 22, 1997, FDA approved finasteride to treat male pattern hair loss.
The Prostate Cancer Prevention Trial (PCPT) showed at a dosage of 5mg per day, as is commonly prescribed for BPH, though much higher than the 1mg 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.[1] However, the cancers that developed in the men taking finasteride looked like they were more likely to grow and spread. The reason for this is not known. The study researchers are continuing to watch these men to see if these cancers truly are more aggressive. At lower doses, this effect is less well-defined.
Recognised side-effects, experienced by around 6%-19% of users, include erectile dysfunction, and less often gynecomastia (breast gland enlargement). [1] In trial studies, side effects ceased after dosage was discontinued.
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[edit] 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
Cipla is also manufacturing finasteride (trade names Fincar and Finpecia), as is Dr. Reddy's (trade names Finax and Finast), Ranbaxy (trade name Finara), and Aleppo Pharmaceutical (trade name Prosteride).
On June 19, 2006, Merck's patents on Proscar and Propecia expired and the FDA approved a first-time generic formulation for finasteride 5 mg tablets.
[edit] Side effects
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. It appears that finasteride can pass into the semen of men, thus, at certain dosages, caution should be used to avoid ingestion of semen during oral sex if a woman is pregnant or may become pregnant.
Finasteride can also be used to mask steroid abuse, and many professional sports have banned finasteride use for this reason.
[edit] Use as a treatment for hair loss
Finasteride is taken orally and has a reported 29–68% success rate (vs 17-45% in patients receiving a placebo). It is effective only for as long as it is taken; the hair gained or maintained is lost within 6-12 months of ceasing therapy (Rossi, 2004). In clinical studies, Propecia, like minoxidil, was shown to work on both the crown area and the hairline,[2] 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.
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 hairloss was more likely related to the loss of estrogen versus a sensitivity to testosterone. Other studies[citation needed] have shown that Propecia is effective for many women with follicular sensitivity to androgens. Many doctors do prescribe it for women, but not without either careful birth control measures or assurance that the woman cannot become pregnant.
[edit] 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.[3] 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 statisticially small.[4] Some people have unsuccessfully petitioned the FDA to re-examine the approved dosage in light of the statistical evidence and unknown long-term risks.[5] The FDA responded and said that just because the level of DHT found in the scalp was not signifigantly 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.[5]
Supporters of Propecia respond that while the drug must be taken for a lifetime in order to avoid losing hair, future treatments are widely expected by baldness specialists to replace Propecia, which would end the need for continued use. In addition, Propecia is widely considered safe enough to prescribe by health professionals, and is one of the only two FDA-approved baldness treatment products on the market.
[edit] 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) cause 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.
- 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, Pat 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]
[edit] References
- http://www.phc.vcu.edu/Feature/oldfeature/finasteride/finasteride.html by Cynthia S. Dowd, Ph.D.
- ^ "Can Prostate Cancer Be Prevented?" American Cancer Society, May 25, 2005.
- ^ 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.
- ^ UC Berkeley Wellness Letter. Avacor. Retrieved on 2006-08-09.
- ^ Center for Drug Evaluation and Research, Application Number NDA 20-788 (PDF). U.S. Food and Drug Administration.
- ^ a b Letter to Dr. Sherman Frankel, University of Pennsylvania (PDF). U.S. Food and Drug Administration.
[edit] See also
[edit] External links
- Propecia (manufacturer's website)
- Proscar (manufacturer's website)
- Rogaine (manufacturer's website)
- Avacor (manufacturer's website)
| Merck & Co., Inc. |
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Corporate Directors: Lawrence Bossidy | William Bowen | Richard Clark | Johnnetta Cole | William Harrison | William Kelley | Rochelle Lazarus | Thomas Shenk | Anne Tatlock | Samuel Thier | Wendell Weeks | Peter Wendell |
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Key products: Indinavir | Aprepitant | Alendronate | Rizatriptan | Finasteride | Montelukast | Rofecoxib | Ezetimibe/simvastatin | Ezetimibe | Simvastatin | The Merck Index | The Merck Manual |
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Annual Revenue: $22.9 billion USD ( |
| Urologicals (G04) edit | ||
|---|---|---|
| Acidifiers: | ||
| Urinary antispasmodics: |
Darifenacin, Emepronium, Flavoxate, Meladrazine, Oxybutynin, Propiverine, Solifenacin, Terodiline, Tolterodine, Trospium |
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| For erectile dysfunction: |
Alprostadil, Apomorphine, Moxisylyte, Papaverine, Phentolamine, Sildenafil, Tadalafil, Vardenafil, Yohimbine |
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| Other urologicals: |
Acetohydroxamic acid, Collagen, Dimethyl sulfoxide, Magnesium hydroxide, Phenazopyridine, Phenyl salicylate, Succinimide |
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| For benign prostatic hypertrophy: |
5α-reductase inhibitors: Dutasteride, Finasteride |
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