500 microgram capsules
Approved indication: benign prostatic hyperplasia
Australian Medicines Handbook section 13.2.2
Although surgery is the definitive treatment for benign prostatic hyperplasia, some patients can be managed with drugs (see 'Drug treatment of benign prostatic hypertrophy', Aust Prescr 1995;18:30-2). The drug treatments include finasteride which inhibits the conversion of testosterone to dihydrotestosterone. This androgen is thought to be responsible for stimulating the growth of the prostate.
Like finasteride, dutasteride is a 5-alpha reductase inhibitor. Finasteride mainly inhibits the type II enzyme found in the prostate, while dutasteride also inhibits the type I enzyme found in the liver and skin. After two weeks of treatment with dutasteride there is a reduction of up to 90% in the concentration of dihydrotestosterone.
The bioavailability of the drug varies from 40% to 94% and it is extensively metabolised. Although cytochrome P450 3A4 is involved in the metabolism, few specific studies of interactions have been carried out in patients. There is a potential for interactions with other drugs metabolised by this enzyme. Most of the metabolites are excreted in the faeces. The half-life of the drug is up to five weeks so it remains in the body for several months after treatment stops. The onset of the full treatment effect is also slow.
In placebo-controlled clinical trials the efficacy of dutasteride has been evaluated using symptom scores in 4325 men. At the start of the studies the average score was 17/35. After two years of treatment this score was significantly reduced by 4.5 points. Dutasteride significantly reduced the volume of the prostate gland. It also significantly improved the urinary flow rate and reduced the risk of acute urinary retention.1 These effects continued during a two-year open-label extension of the trials.2
Dutasteride has adverse effects on sexual function. Patients may develop a decreased libido, ejaculation disorders or impotence. Serum testosterone may increase, but prostate specific antigen concentrations will be reduced by dutasteride.
As dutasteride may affect the development of a male fetus the capsules should not be handled by pregnant women.
Like finasteride (see 'The price of urine', Aust Prescr 1995;18:26-7), the effect of dutasteride is modest. A placebo can improve a patient's symptom score by 2.3 points and the statistically significant change in urinary flow rate is only 1.3 mL/second greater than placebo.1 Drug treatment should therefore only be used if self-management strategies do not work.
The Transparency Score is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.
- Hoefner K, Andriole G; ARIA3001, ARIA3002, and ARIA3003 Study Investigators. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002;60:434-41 .
- Debruyne F, van Erps P, Reis M, Tammela TLJ, Roehrborn C; ARIA3001, ARIA3002 and ARIB3003 Study Investigators. Efficacy and safety of long-term treatment with the dual 5Î±-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia. Eur Urol 2004;46:488-95 .
Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.