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ABSTRACT

Finasteride 1 mg (Propecia®, Merck) was approved by the US FDA December, 1997 for the treatment of male pattern hair loss (androgenetic alopecia, AGA) in men only. Safety and efficacy were demonstrated in men between 18 and 41 years of age with mild to moderate hair loss of the vertex and anterior mid-scalp area. Efficacy in bi-temporal recession has not been established.¹ Propecia® is not approved for use in women or children. Finasteride has been approved for this same indication in Australia, Argentina, Mexico and New Zealand and approval is being sought in more than 20 other countries.

Key Words: hair loss, Finasteride, Propecia, dihydrotestosterone

Hair loss has a significant psychosocial effect on some men. In these men, safe and effective treatment of hair loss is important to quality of life.²

Efficacy of finasteride¹

Efficacy has been demonstrated in three double-blind, randomized, placebo-controlled studies in 1,879 men between 18–41 years of age with mild to moderate androgenetic alopecia. Two of the studies enrolled men with mild to moderate vertex loss, the third investigated mild to moderate loss in the anterior mid-scalp area with or without vertex balding. Primary end-points were hair count (assessed by photographic enlargements of a representative area of active hair loss) and patient selfassessment; secondary end-points were investigator assessment and ratings of global photography.

Clinical improvement was seen as early as three months in the patients treated with finasteride and led to a net increase in scalp hair count and hair regrowth. These effects have been maintained through two years in these studies and for up to three years in open-extension studies. Improvements have been seen across all racial groups.

Side effects

Adverse effects are minimal. Results in men treated with finasteride for benign prostatic hyperplasia, where five times the dose has been studied in men for up to 6 years, have revealed no long-term problems or new effects over the longer period. In patients with AGA treated with 1 mg of finasteride daily for 12 months in controlled studies, 1.4% of finasteride treated patients versus 1.6% of placebo treated patients discontinued therapy because of adverse drug experiences, and 1.2% of finasteride treated patients versus 0.9% of placebo treated patients discontinued because of drug-related sexual experiences. Sexually related adverse effects reported as possibly, probably or definitely drug or placebo related were decreased libido, erectile dysfunction and ejaculation disorder. Analysis showed that 4% of 945 men treated with finasteride and 2% of 934 men treated with placebo reported one or more of these adverse effects (p= 0.04). These problems resolved in all men who stopped therapy with finasteride because of these effects, and in 58% of those who continued therapy.¹

In older men with benign prostatic hyperplasia, PSA levels are decreased by 50% with finasteride therapy and consideration should be given to doubling the test level returned by men undergoing this test while taking finasteride.¹

Contraindications

Finasteride is not indicated for use in women.¹

Pregnancy Use of finasteride is contraindicated in women when they are pregnant or potentially may be pregnant, because of the risk to a male fetus.¹

Precautions1

Liver function abnormalities Finasteride is metabolized extensively in the liver and caution should be used when treating patients with liver function abnormalities.

Handling Pregnant or potentially pregnant women should not handle crushed or broken Propecia® tablets because of the possibility of absorption of drug and subsequent potential risk to a male fetus.¹

Pharmacokinetics

The bioavailability of finasteride is not affected by food. Following oral dosage of finasteride, a mean of 39% (almost entirely as metabolites) is excreted in the urine and 57% in the feces. The metabolites in the urine possess no more than 20% of the 5α-reductase inhibitory activity of finasteride.3 At steady state, the mean terminal half-life of elimination is approximately 5–6 hours in men 18–60 years of age, increasing to 8 hours in men more than 70 years of age. No dosage adjustment is necessary in the elderly or in patients with renal insufficiency.¹

Drug interactions

No drug interactions of clinical importance have been identified. Finasteride does not appear to affect the cytochrome P450-linked drug metabolizing system.¹

Mechanism of action

It is thought that finasteride interrupts a key step in the pathogenesis of AGA, in those patients who are genetically predisposed. Finasteride is a preferential, competitive inhibitor of the intracellular, Type II, 5α-reductase isoenzyme which converts testosterone into dihydrotestosterone (DHT), a more potent androgen. In humans, the Type II 5α-reductase isoenzyme is primarily found in the root sheath of the hair follicle, prostate, seminal vesicles, epididymis, fetal genital skin and in fibroblasts from normal adult genital skin^1,3, as well as liver, and is responsible for two-thirds of circulating DHT. In target organs, finasteride treatment is thought to result in selective androgen deprivation affecting DHT without lowering circulating levels of testosterone, thus preserving the desired androgen mediated effects on muscle strength, bone density and sexual function.⁴ In AGA, the balding scalp contains miniaturized hair follicles and increased amounts of DHT compared with non balding scalp, and finasteride treatment produces inhibition of the isoenzyme, resulting in a rapid reduction in scalp and serum DHT concentrations.¹

Finasteride has no affinity for the androgen receptor, no androgenic, anti-androgenic, estrogenic, anti-estrogen or progestational effects, no effect on cortisol, thyroidstimulating or thyroxine levels, and no effect on plasma lipid profile or bone mineral density. Circulating levels of testosterone and estradiol are increased by 15% but remain within the physiologic range.¹

Dosage and administration

The recommended dosage is one mg once a day. Because of the psychosocial impact of hair loss, it is important to explain what the patient may expect in terms of continuing hair loss. The response to any therapy may be slow and may include hair regrowth and/or retardation of further thinning. ^5,6 In general, daily use for at least three months or more is necessary before benefit is observed. Continued use is recommended to sustain benefit as withdrawal of treatment leads to reversal of effect within 12 months.¹

Treatment of male pattern hair loss		Cost to the Pharmacist
Finasteride, Propecia®	1 mg tablet / day	US$47 / month7,8
Minoxidil 2%, Rogaine®, & others	apply lotion twice daily	US$11-23 / month7,8
5%, Rogaine Extra Strength for Men®		US$28 per month
Hair transplants	multiple sessions are usual	US$3500-10,000 / session6

There has been some controversy in newspapers and on the Internet about the cost of 1mg tablets of Propecia® compared to the cost of 5mg tablets of Proscar.® The New York Times on January 20th, 1998 used the heading, “New Baldness Drug Is Older Product at a Premium Price” and highlighted the statement that “A prostate treatment grows in value when it grows hair.” Some price difference is reasonable, as Merck has had to finance development and clinical trials for this new indication and their costs must amount to at least tens of millions of dollars. While some user groups have been advocating splitting the 5 mg tablets, there is no data on the stability of tablet fragments, or the efficacy of this approach as Proscar® tablets have only been approved for the treatment of benign prostatic hyperplasia.

Future developments

Finasteride may hold promise for other DHT-mediated disorders such as facial hirsutism and frontal alopecia.⁹ Several companies are developing combination Type I and Type II 5α-reductase inhibitors which may be regarded as candidates for treatment of androgen-dependent skin disorders such as seborrhea, acne, hirsutism and/or androgenetic alopecia.⁹

The place of finasteride in therapy

A recent review in the Medical Letter™ concluded that finasteride can produce a modest increase in hair on the scalps of young men with mild-to-moderate hair loss.7 They also note that treatment must be continued indefinitely to maintain the effect.⁷

There is no question that oral finasteride (Propecia®) is effective in the oral treatment of AGA. Oral finasteride has now become the standard against which all future therapies for male AGA should be compared.
Dr. Jerry Shapiro, Vancouver

This is the first time that a systemic agent has been approved for use to treat male pattern hair loss. On the basis of our experience with minoxidil, if patients get sufficient hair growth for a cosmetic improvement, they will use finasteride on a continuing basis. In this respect, treating male pattern hair loss is little different to treating many other chronic diseases!
Dr. Stuart Maddin, Editor

Drug Treatments Introduced in 1997

Indication	Generic / Trade Name		Company	Country
Actinic Keratosis	Hyal-CT-1101	Solarase	Hyal Pharmaceuticals	UK
Anti-acne	Tazarotene	Tazorac	Allergan	USA
	Tretinoin	Retin-A-micro	Advanced Polymer System & Ortho-McNeil	USA
	Tretinoin	Avita	Penederm	USA
Anti-eczema	Fluticasone	Fluticasone	Glaxo Wellcome	USA
Antifungal	Amphotericin B	Abelcet	The Liposome Co.	Austria, France
Antiherpetic	Penciclovir	Vectavir	SmithKline Beecham	Germany
Antipsoriatic	Acitretin	Soriatane	Roche	USA
	Tazarotene	Tazorac	Allergan	Canada, Germany, Italy, UK, USA
(severe recalcitrant)	Cyclosporine	Neoral	Novartis	USA
Antiviral	Imiquimod	Aldara	3M Pharmaceuticals	USA
	Penciclovir	Denavir	SmithKline Beecham	USA
	Valaciclovir	Valtrex	Glaxo Wellcome	Australia, Spain
Aphthous ulcer	Amlexanox	Apthasol	Block Drugs	USA
Kaposi’s Sarcoma	Daunorubicin	DaunoXome	Nexstar	Russia
Male pattern baldness	Finasteride	Propecia	Merck & Co.	USA
	Minoxidil 5%	Rogaine	Pharmacia Upjohn	USA
Malignant melanoma	Virulizin	Virulizin	Imutec Pharma	Mexico
Wound healing	Human Skin Equivalent	Apligraf	Novartis	Canada
	Skin substitute	Dermagraft-TC	Advanced Tissue Sciences	USA
(diabetic foot ulcer)	Becaplermin	Regranex	Rhone-Poulenc Rorer / J&J / Chiron	USA
(diabetic foot ulcers)	Artificial skin	Dermagraft	Smith & Nephew	Canada

References

1. US Physician Package Insert.
2. Cash TF. The psychological effects of androgenetic alopecia in men. J Am Acad Dermatol 1992; 26: 926-931.
3. Sudduth SL, Koronkowski MJ. Finasteride: the first 5 alpha-reductase inhibitor. Pharmacotherapy 1993; 13: 309-25.
4. Gormley GJ. Finasteride: a clinical review. Biomed Pharmacother 1995; 49: 319-24.
5. Drake LA, Dinehart SM, Farmer ER et al. Guidelines of care for androgenetic alopecia. J Am Acad Dermatol 1996;35: 465-9.
6. Maddin SM. Editor.
7. Propecia and Rogaine Extra Strength for alopecia. Med Letter 1998; 40: 25-27.
8. Drug Topics Red Book Update, February 1998.
9. Chen W, Zouboulis CC, Orfanos CE. The 5 alpha-reductase system and its inhibitors. Recent developments and its perspective in treating androgendependent skin. Dermatology 1996; 193: 177-184.

In this issue:

1. Finasteride for Male Pattern Hair Loss
2. Tinea capitis
3. Update on Drugs and Drug News - Number 4 1998