Dutasteride

Dutasteride

Systematic (IUPAC) name

Dutasteride (marketed as Avodart, Avidart, Avolve, Duagen, Dutas, Dutagen, Duprost) is a 5-alpha-reductase inhibitor, a drug which inhibits the conversion of testosterone into dihydrotestosterone (DHT). It is used to treat conditions caused by DHT, such as benign prostatic hyperplasia (BPH). Avodart is manufactured and marketed by GlaxoSmithKline.

Classification and Method of Action

Dutasteride belongs to a class of drugs called 5-alpha-reductase inhibitors, which block the action of the 5-alpha-reductase enzymes that convert testosterone into dihydrotestosterone (DHT). Finasteride also belongs to this group. Dutasteride inhibits both isoforms of 5-alpha reductase, while finasteride inhibits only one. But a clinical study done by GlaxoSmithKline, the EPICS trial, did not find dutasteride to be more effective than finasteride in treating BPH.

Uses

While dutasteride is only officially approved to treat enlargement of the prostate gland (at a dose of 0.5mg/day), phase I and II clinical trials for dutasteride as a hair loss drug were also undertaken, but called off in late 2002. The reason the trials were called off is not publicly known. Industry sources speculate that Avodart would have been seen as too similar to Propecia to have proved profitable as a hair loss treatment. However, phase II results indicated that dutasteride 2.5mg/day generated a superior hair count to finasteride 5mg at 12 and 24 weeks.

In December 2006, GlaxoSmithKline started a new Phase III, six month study in Korea to test the safety, tolerability and effectiveness of a once-daily dose of dutasteride (0.5mg) for the treatment of male pattern baldness in the vertex region of the scalp (types IIIv, IV and V on the Hamilton-Norwood scale). The future impact that this study will have on the FDA's approval or disapproval of Avodart for the treatment of male pattern baldness in the United States is yet to be determined.

Dutasteride is also in development for Prostate cancer risk reduction.

Side Effects

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.

The most common adverse reactions reported in subjects receiving AVODART were impotence, decreased libido, breast disorders (including gynecomastia), and ejaculation disorders. Study withdrawal due to adverse reactions occurred in 4% of subjects receiving AVODART and 3% of subjects receiving placebo. The most common adverse reaction leading to study withdrawal was impotence (1%).

(Before Avodart)

(After 6 months treatment with Avodart)

Teratogenic effect

The teratogenic effect from Dutasteride is a very large risk for male children. The effect would be similar to 5-alpha-reductase deficiency, where a developing male child naturally is deficient in 5-alpha reductase type 2, and thus unable to synthesize DHT Type 2. As Dutasteride blocks the same process (although type 1 and 2 DHT) a developing male would have this deficiency as a result of medication, rather than simply naturally.

Women who are pregnant or in their childbearing years, or children should not be allowed to handle the capsules. This can cause major birth defects.