USE OF AVODART IN ANDROGENETIC ALOPECIA OR MALE PATTERN BALDNESS (HAIRLOSS)


SUMMARY 1. The treatment of androgenetic alopecia is not an FDA-approved indication for Avodart (dutasteride). LTherefore, GlaxoSmithKline may not make recommendations on the use of Avodart for the purpose. 2. Avodart inhibits the conversion of testosterone to dihydrotestosterone (DHT) resulting in decreased serum DHT concentrations. By this mechanism, Avodart appears to interrupt a key process in the development of androgenetic alopecia (AGA), also known as male pattern hari loss (MPHL). 3. A phase II, multi-center double blind, placebo controlled study was conducted in 416 males with AGA, ages 21-45 years, to evaluate the dose response relationship of Avodart on hair growth. Repeated doses of Avodart (0.05mg), 0.5mg, and 2.5mg daily) were compated to placebo for 6 months. Safety and tolerability of the varying doses of Avodart and finasteride 5mg daily compared with placebo were also investigated. 4. A dose related increase in hair count was seen at week 12 and 24 in patients receiving Avodart, significant increases were also observed in the finasteride treatment group. The increase in hari count was maintained after the cessation of treatment aw=t week 36 (12 weeks after medication discontinuation) in the Avodart 0.5mg and 2.5mg treatment groups, but not in the finasteride or Avodart 0.05mg and 0.1mg treatment groups. 5. The most common drug-related adverse events were decreased libido experienced by 13% of subjects receiving Avodart 2.5mg/day, followed by headaches experienced by 8% of the Avodart 0.1mg/day group and 6% of the Avodart 0.5mg/day and 2.5mg/day group. 6. No large, prospective clinical trials have evaluated the use of avodart for AGA. 7. Avodart is indicated for the treatment of sympotoatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve symptoms, reduce the risk of acute urinary tetention, and reduce the risk of the neeed for BPH-related surgery. Avodart is contraindicated for use in women and children and for patients with knowhn hypersensitivity to dutasteide, other 5?-reductase inhibitors, or any component of the preparation.

Some information contained in this response may be outside the approved prescribing information for Avodart . This response is not intended to offer recommendations for administerin Avodart in a manner inconsistent with its approved labeling. In order for GlaxoSmithKline to monitor the safety of avodart, we encourage healthcare professionals to report adverse events or suspected overdoses to the company at 888-825-5249. Please consult the Prescribing Information for Avodart.

Background

Androgenetic alopecia (AGA), also known as male pattern hair loss (MPHL), is the most common form of hair loss, affecting approximately 50% of Caucasians over the age of 40 years (1). In males, AGA can begin as early as late adosescence; however, the usual onset is at around the age of 30 years (1). AGA results from naturally circulating androgens which progressively transform large terminal scalp follicles to smaller vellus ones, thus resulting in a visibly less dense scalp (2).

Testosterone is the major circulating androgen in the body, but must be converted to dihydrotestosterone (DHT) via the enzyme 5 a -reductase in order to be active in the skin (3). Studies have shown that men with 5 a -reductase deficiency do not develop AGA (*3,4). Therefore, 5 a -reductase inhibitors have been evaluated for the treatment of AGA due to their ability to inhibit the conversion of testosterone to dihydrotestosterone (3,5). Two isoforms of 5 a -reductase are known, type 1 and type 2. Type 2 is predominately located in human genital tissue. Type 1 is distributed throughout the body, and predominates in the skin and scalp (3).

Avodart is a competitive inhibitor of 5 a -reductase, the enzyme responsible for the conversion of testosterone eo dihydrotestosterone (DHT) in the prostate. It inhibits both enzyme types 1 and 2 and is incdicated for the treatment of symptomatic BPH in men with an enlarged prostate to improve symptoms, reduce the risk of acute urinary retention, and reduce the risk of the need for BPH-related sur4gery. Avodart is contraindicated for use in women and children and for patients with known hypersensitivity to dutatsteride, other 5 a -reductase inhibitors, or any component of the preparation (6).

One clinical trial evaluating the use of Avodart in AGA has been conducted and is discussed below. No large, prospective clinical trials have evaluated the use of Avodart for this use.