Long-term safety data for dutasteride comes primarily from the 4-year REDUCE trial (8,231 men) and the 4-year CombAT trial (4,844 men), plus post-marketing surveillance. Sexual adverse events were the most common, and their incidence fell with time on treatment. The current FDA label adds that these reactions may persist after treatment is discontinued, and that the role of dutasteride in that persistence is unknown. Two signals did emerge over four years and are carried in the FDA label: an excess of Gleason 8-10 prostate cancer in REDUCE, and a numerical excess of composite cardiac failure whose clinical significance the label states is unknown.
REDUCE Trial Safety Data (4 Years)
- Sexual adverse events were front-loaded. In the pooled placebo-controlled BPH trials, impotence ran 4.7% on dutasteride against 1.7% on placebo in months 0-6, and 0.8% against 0.9% by months 19-24. Falling incidence during treatment is not the same as resolution: the current label states these reactions may persist after discontinuation
- Breast disorders (including breast tenderness and enlargement): 0.5%, 0.8%, 1.1% and 0.6% on dutasteride across months 0-6, 7-12, 13-18 and 19-24, against 0.2%, 0.3%, 0.3% and 0.1% on placebo
- No imbalance in overall cardiovascular adverse events, but composite cardiac failure occurred in 0.6% (26 of 4,105) on dutasteride against 0.4% (15 of 4,126) on placebo in REDUCE. The FDA label states the clinical significance is unknown and no causal relationship has been established
- Gleason 8-10 prostate cancer was found in 1.0% of men on dutasteride against 0.5% on placebo over the four years of REDUCE
- PSA reduced by approximately 50% (important for prostate cancer screening interpretation)
CombAT Trial Safety Data (4 Years)
The CombAT trial confirmed similar findings in the BPH population. The combination of dutasteride and tamsulosin had a higher rate of sexual side effects than either drug alone. Composite cardiac failure was also higher on the combination (12 of 1,610, 0.7%) than on either monotherapy (dutasteride 2 of 1,623, 0.1%; tamsulosin 9 of 1,611, 0.6%).
Long-term side effects · Side effects overview · All studies
Sources
- Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362(13):1192-202. PubMed 20357281
- Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123-31. PubMed 19825505
- FDA. Avodart (dutasteride) Prescribing Information, Sections 6.1 and 5.2. NDA 021319.
- FDA. Avodart Prescribing Information, current revision, Table 1 footnote (persistence of sexual adverse reactions). NDA 021319.