INDICATIONS

Both dutasteride and finasteride arrest the disease process of men with BPH and an enlarged prostate and are indicated to improve symptoms, reduce the risk of AUR, and reduce the need for BPH-related surgery. (14, 15)

ADVERSE EVENTS 

Without direct, comparative clinical trials, it is not possible to determine the comparative incidence of adverse events between finasteride and dutasteride. Differences in reported adverse event rates may reflect differences in patient populations, trial design, or methods of adverse event collection and coding. Please refer to the Prescribing Information for both Proscar and Avodart for reports of adverse event experienced with each agent during the clinical trials.

Since finasteride has been available in the U.S. since 1992, longer-term safety data are available with finasteride. Both agents have a wide margin of safety, as demonstrated by the short-term administration of much higher doses than those approved for the treatment of BPH. In clinical trials, doses of up to 80 mg finasteride daily or 5 mg dutasteride daily for 12 weeks have been well-tolerated (14, 15).

For both agents, the most frequently reported drug-related adverse events were related to sexual function. These included impotence, decreased libido, decreased volume of ejaculation and ejaculation disorders, and breast tenderness and /or enlargement. For both agents, the onset of drug-related sexual adverse events appears to diminish with time, and there is no evidence of increased adverse events with increased duration of therapy. (14, 15, 28)

SHORT-TERM COMPARATIVE CLINICAL TRIAL 

EPICS (Enlarged Prostate International Comparator Study) was a randomized double-blind active-controlled trial that compared 12 months of dutasteride and finasteride therapy in 27 European countries.

The study was conducted to fulfill European registration requirements. The primary objective of the study was the change in baseline prostate volume at 1 year. Safety and tolerability data were also obtained. Patients with BPH (N= 1630) were randomized to receive either dutasteride 0.5 mg once daily (n=813) or finasteride 5.0 mg once daily (n=817) for 12 months. Of the patients randomized, 1454 completed the 12-month double-blind phase (719 dutasteride and 735 finasteride). (32)

Patients enrolled were males > 50 years old with BPH according to medical history and physical examination including a DRE, an AUA-SI score > 12, prostate volume > 30cc as determined by transrectal ultrasound, and serum PSA > 1.5 but < 10ng/mL, urinary flow rate < 15 mL/sec, and a minimum voided volume > 125 mL. Patients were excluded if they had a post-void residual volume > 250 mL or a PSA < 1.5ng.mL or > 10ng/mL.

For the intent-to treat population, prostate volume was reduced from baseline in both the dutasteride and finasteride groups at month 12. The difference between the two agents was not statistically significant. Dutasteride produced numerically but not statistically significant greater improvements in symptoms and urinary flow rates compared with finasteride. PSA levels were also decreased from baseline to a similar degree in both treatment groups. (32)

Although fewer drug-related sexual adverse events occurred in patients receiving dutasteride than finasteride, there were no significant differences betwe3en the two drugs (17% in the dutasteride group compared with 20% in finasteride-treated patients). The most frequent drug-related adverse events were sexual in nature and are listed in Table 4.

Table 4. Summary of drug-Related Adverse Events after 1-year of dutasteride or finasteride (32)

Few adverse events led to patient withdrawal from the study (5% of dutasteride patients and 4% of finasteride-treated patients). (32) Thus, dutasteride appeared to be as safe as finasteride for pat9ients with BPH.

Since BPH is a long-term, gradually progressive disease, it is possible that differentiation between the two drugs may not be apparent in a shorter-term trial. It is unknown whether significant differences in clinical outcomes between dutasteride and finasteride would occur with longer treatment duration.

Finally, a brief 3-mnth prospective and consecutive study was conducted to evaluate the onset of symptom relief with Avodart versus Proscar (33). One hundred twenty men with symptomatic BPH were treated with Avodart , followed by and additional 120 men treated consecutively with Proscar for 3 months in each trial. Patients were instructed not to expect any symptomatic benefit until at least 6 months. The American Urological Association Symptom Index (AUA-SI) was used to assess symptom scores at baseline and following 3 months of therapy with each drug.

No significant differences were noted between patients at baseline in terms of age or serum levels of PSA. Among patients who received Avodart there were significantly greater reductions in AUA-SI scores compared with Proscar . Specifically, 68 (57%) of patients experienced no improvement over the 3-month period with Avodart compared with 92 (77%) of patients treated with Proscar . One unit improvements in the AUA-SI (36(30%) and 22 (18%)) and 2-unit improvements (14 (12%) and 5 (4%)) were noted in patients treated with Avodart and Proscar, respectively. A corresponding 3-unit AUA-SI score reduction was noted in 2 (2%) and 1 (1%) of Avodart and Proscar patients, respectively. The estimated difference (with 95% CI; 7.5%, 32.5%; two-sided Fisher's Exact test P < 0.0016). Conclusion drawn from this study must be considered carefully in light of the study design.

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