Avodart Side Effects Severity Distribution by Patient Phenotype

Side effects in months 0 to 6, Avodart vs placebo [1]

What the rates by time on treatment show

The pooled population was aged 47 to 94 years (mean 66) and more than 90% white [1].

• Months 0 to 6: impotence 4.7% vs 1.7%, decreased libido 3.0% vs 1.4%, ejaculation disorders 1.4% vs 0.5%, breast disorders 0.5% vs 0.2% [1].
• Months 7 to 12: impotence 1.4% vs 1.5%, decreased libido 0.7% vs 0.6%, ejaculation disorders 0.5% vs 0.3%, breast disorders 0.8% vs 0.3% [1].
• Months 13 to 18: breast disorders 1.1% vs 0.3%, the highest breast-disorder rate in the table [1].
• Months 19 to 24: every category was within about one percentage point of placebo [1].

A footnote to those sexual reactions says they may persist after treatment is stopped and that the role of dutasteride in that persistence is unknown [1]. Withdrawal because of adverse reactions was 4% on dutasteride vs 3% on placebo, most often for impotence at about 1% [1].

Tamsulosin co-treatment shifts the numbers

In the 4-year CombAT trial of more than 4,800 men with BPH (mean age 66), ejaculation disorders occurred in 11% on dutasteride plus tamsulosin, 2% on dutasteride alone and 4% on tamsulosin alone [1]. In the first six months: ejaculation disorders 7.8% vs 1.0% vs 2.2%, impotence 5.4% vs 4.0% vs 2.6%, decreased libido 4.5% vs 3.1% vs 2.0% and dizziness 1.1% vs 0.5% vs 0.9% [1]. Withdrawal for adverse reactions was 6% on combination vs 4% on either single drug, most often erectile dysfunction at 1% to 1.5% [1].

Younger men taking it for hair loss

Dutasteride is not FDA-approved for hair loss; the only approved use is symptomatic BPH, alone or with tamsulosin [1]. A 2019 meta-analysis of 15 randomized placebo-controlled trials (4,495 men) found a 1.57-fold overall risk of sexual dysfunction with 5-alpha reductase inhibitors; the dutasteride-specific relative risk was 1.37 (95% CI 0.81 to 2.32), which was not statistically significant, and the authors noted that dutasteride trials were few [2]. In a 24-week trial of 917 men aged 20 to 50 with androgenetic alopecia, the number and severity of adverse events were similar across dutasteride doses, finasteride and placebo [3].

CYP3A4 inhibitors and dutasteride exposure

Dutasteride is extensively metabolized by CYP3A4 and CYP3A5, and the effect of potent CYP3A4 inhibitors has not been studied; the label advises caution with potent, chronic inhibitors such as ritonavir [1]. Verapamil and diltiazem reduce dutasteride clearance and raise exposure, a change the label does not consider clinically significant and which needs no dose adjustment [1].