Dutasteride (Avodart) has been FDA-approved since 20 November 2001 and remains on the market with its approved indication intact. Its most frequently reported adverse reactions are sexual: in the pooled placebo-controlled BPH trials, impotence was reported by 4.7% of men on dutasteride during months 0-6 against 1.7% on placebo, decreased libido by 3.0% against 1.4%, and ejaculation disorders by 1.4% against 0.5%, with rates falling in each later interval. The label also carries two findings that deserve to be read rather than skipped: a higher incidence of Gleason 8-10 prostate cancer in the REDUCE trial, and a numerical imbalance in cardiac failure. Dutasteride is contraindicated in pregnancy, in women of childbearing potential, and in children. It is FDA-approved in the United States for benign prostatic hyperplasia only; use for hair loss is off-label.
FDA Approval and Clinical Trial Safety Data
Dutasteride received FDA approval on 20 November 2001 under NDA 021319. The label describes three identical 2-year, placebo-controlled, double-blind Phase 3 studies in over 4,300 men with BPH, each followed by a 2-year open-label extension. During the double-blind period 2,167 men were exposed to dutasteride, including 1,772 for 1 year and 1,510 for 2 years; counting the extensions, 1,009 were exposed for 3 years and 812 for 4 years.
Two further 4-year trials add to that base. CombAT randomised over 4,800 men to dutasteride, tamsulosin or the combination. REDUCE was a separate 4-year, placebo-controlled trial in 8,231 men aged 50 to 75 with a PSA of 2.5 to 10 ng/mL and a negative prostate biopsy, designed to test whether dutasteride reduced prostate cancer incidence. REDUCE was not an extension of the BPH trials, and dutasteride is not approved for the prevention of prostate cancer.
Common Side Effects: Incidence Rates
| Side Effect | Dutasteride (months 0-6) | Placebo (months 0-6) |
|---|---|---|
| Impotence (erectile dysfunction) | 4.7% | 1.7% |
| Decreased libido | 3.0% | 1.4% |
| Ejaculation disorders | 1.4% | 0.5% |
| Breast disorders (enlargement or tenderness) | 0.5% | 0.2% |
These are the figures from Table 1 of the label, which reports by 6-month interval rather than by year. Rates fell in each successive interval. Impotence, for example, went from 4.7% at months 0-6 to 1.4%, 1.0% and 0.8%, against placebo figures of 1.7%, 1.5%, 0.5% and 0.9%. Across the three pivotal trials the label reports no evidence of increased sexual adverse reactions or breast disorders with increased duration of treatment. Study withdrawal because of an adverse reaction occurred in 4% of men on dutasteride and 3% on placebo, and the most common reaction leading to withdrawal was impotence, at 1%.
Serious Safety Warnings
⚠️ Contraindicated in Pregnancy: The FDA label lists pregnancy and women of childbearing potential among its contraindications, alongside pediatric patients and known hypersensitivity to dutasteride or other 5-alpha reductase inhibitors. Dutasteride is absorbed through the skin, so women who are pregnant or could become pregnant must not handle the capsules; if contact is made with a leaking capsule, the area should be washed immediately with soap and water. In animal reproduction and developmental toxicity studies, dutasteride inhibited normal development of the external genitalia in male fetuses.
⚠️ Prostate Cancer Detection: Dutasteride reduces serum PSA (prostate-specific antigen) by approximately 50% within 3 to 6 months of treatment. A new PSA baseline should be established at least 3 months after starting, and PSA monitored periodically thereafter. Any confirmed increase from the lowest PSA value recorded on dutasteride should be evaluated, even if the value is still within the normal range for untreated men. To interpret an isolated PSA value after 3 months or more of treatment, the label directs that the value be doubled for comparison with normal ranges.
⚠️ High-Grade Prostate Cancer: In the 4-year REDUCE trial there was a higher incidence of Gleason score 8-10 prostate cancer in men receiving dutasteride, 1.0%, than in men on placebo, 0.5%. The label carries this in Warnings and Precautions, section 5.2; Avodart has no boxed warning. A 7-year placebo-controlled trial of finasteride 5 mg produced a similar pattern, 1.8% versus 1.1%. The label states that 5-alpha reductase inhibitors may increase the risk of developing high-grade prostate cancer, and that whether prostate-volume reduction or study-related factors influenced these results “has not been established.” Discuss the implications with your urologist before starting dutasteride if you have prostate cancer risk factors.
Long-Term Safety: What 4 Years of Data Show
REDUCE followed 8,231 men for 4 years and CombAT followed over 4,800 for the same period. Taken together with the label’s own pharmacodynamic studies, the long-term picture is this:
- Cardiac failure: a numerical imbalance was seen in both trials. In REDUCE, the composite term cardiac failure occurred in 0.6% of men on dutasteride (26 of 4,105) against 0.4% on placebo (15 of 4,126). In CombAT, it occurred in 0.7% of the combination group (12 of 1,610), 0.1% on dutasteride alone (2 of 1,623) and 0.6% on tamsulosin alone (9 of 1,611). The label states most affected subjects had co-morbidities associated with cardiac failure risk, that the clinical significance of the imbalance is unknown, that no causal relationship has been established, and that no imbalance was seen in overall cardiovascular adverse events
- Sexual adverse reactions: no evidence of an increase with increased duration of treatment across the three 4-year pivotal trials
- Bone mineral density: no change measured by DXA after 52 weeks in healthy volunteers, against either placebo or baseline
- Lipids: total cholesterol, LDL, HDL and triglycerides were unaffected after 52 weeks in healthy volunteers
- Mood: depressed mood appears among the adverse reactions identified after approval. Because such reports are voluntary and come from a population of uncertain size, the label states their frequency cannot be reliably estimated and a causal relationship cannot always be established
- Liver: the effect of hepatic impairment on dutasteride pharmacokinetics has not been studied. Because dutasteride is extensively metabolized, exposure could be higher in hepatically impaired patients
Who Should Not Take Dutasteride
- Women who are pregnant (contraindicated)
- Women of childbearing potential, including nursing women (contraindicated). The label adds that dutasteride is not indicated for use in any other woman
- Pediatric patients (contraindicated; safety and effectiveness have not been established)
- Patients with previously demonstrated, clinically significant hypersensitivity to dutasteride or other 5-alpha reductase inhibitors, including serious skin reactions and angioedema (contraindicated)
- Patients with hepatic impairment: not a contraindication, but the effect on dutasteride pharmacokinetics has not been studied and exposure could be higher. Raise it with your prescriber
Dutasteride Safety vs Finasteride
The two labels list the same broad categories of sexual adverse reaction, though the trials behind them differ in population and design and no head-to-head safety trial is cited in either. The clearest difference is pharmacokinetic. Dutasteride’s terminal elimination half-life is approximately 5 weeks, with serum concentrations detectable for up to 4 to 6 months after the last dose. The Propecia label gives a mean terminal half-life for finasteride of approximately 5 to 6 hours in men aged 18 to 60 and about 8 hours in men over 70. If you develop an adverse effect and stop, dutasteride takes months to clear where finasteride takes days. Full dutasteride vs finasteride comparison · Discontinuation guide.
Sources
- Andriole GL, et al. (REDUCE trial). N Engl J Med. 2010;362(13):1192-202. PubMed
- FDA. Avodart (dutasteride) prescribing information, NDA 021319 (revision s023/s025): Contraindications, Warnings and Precautions, Adverse Reactions and Clinical Pharmacology. accessdata.fda.gov
- FDA. Avodart (dutasteride) prescribing information, current label (revision s032), Adverse Reactions Table 1 footnote and Postmarketing Experience. accessdata.fda.gov
- Roehrborn CG, 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
- FDA. Propecia (finasteride) prescribing information, Clinical Pharmacology. accessdata.fda.gov