Avodart Month-by-Month: What to Expect in the First 3 Months

Month 1: the hormone effect comes first

Median serum DHT is down 85% after one week and 90% after two weeks of 0.5 mg once daily, and median serum testosterone rises about 19% to 26% while staying within the physiologic range [1]. Blood levels of the drug itself keep climbing after that: dutasteride reaches about 65% of steady state after one month and about 90% after three months, with a terminal half-life of roughly five weeks at steady state [1].

The Avodart label reports adverse reactions by multi-month blocks rather than by week. In months 0 to 6, impotence was reported in 4.7% on dutasteride versus 1.7% on placebo, decreased libido in 3.0% versus 1.4%, and ejaculation disorders in 1.4% versus 0.5%. Breast disorders (enlargement or tenderness) were 0.5% versus 0.2% in that block, with their highest reported rate later, at months 13 to 18 (1.1% versus 0.3%) [1]. The label does not say which week inside the first block those reactions appear.

The 2014 hair-loss trial in 917 men used hair count at week 24 as its primary endpoint [3].

Month 2: accumulation

Between the one-month and three-month marks, dutasteride moves from roughly 65% to roughly 90% of steady state, and average steady-state serum concentration is about 40 ng/mL after a year of dosing [1].

The hair-loss trial abstracts report hair count and width at set endpoints, and neither describes a shedding phase [3][2].

For side effects, the label reports sexual and breast-related reactions during months 0 to 6 without identifying which occurred in month two, and it adds that the sexual reactions may persist after treatment is stopped, with the role of dutasteride in any persistence unknown [1]. A meta-analysis of 15 randomized placebo-controlled trials (4,495 men) of finasteride 1 mg or dutasteride 0.5 mg for hair loss found a 1.57-fold overall relative risk of sexual dysfunction; for dutasteride 0.5 mg alone the 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 [4].

Month 3: near steady state, and a PSA baseline

By three months the drug is about 90% of the way to steady state [1], and the label's PSA instruction applies. The Avodart label says serum PSA falls by about 50% within 3 to 6 months of treatment and that a new PSA baseline should be established at least 3 months after starting [1]. For an isolated PSA in a man treated 3 months or longer, the label says the value should be doubled for comparison with normal ranges in untreated men, and any confirmed increase from the lowest on-treatment value should be evaluated even when the number is still within the normal range [1]. Percent free PSA remains constant [1].

For hair, the 0.5 mg trial reported its primary result at week 24, not at month three. That 2014 trial randomized 917 men aged 20 to 50 to dutasteride 0.02, 0.1 or 0.5 mg, finasteride 1 mg or placebo for 24 weeks: hair count and width rose dose-dependently, and dutasteride 0.5 mg increased hair count more than finasteride (P=.003) and more than placebo (P<.001) at week 24 [3]. The 2006 trial randomized 416 men aged 21 to 45 to dutasteride 0.05, 0.1, 0.5 or 2.5 mg, finasteride 5 mg or placebo for 24 weeks: dutasteride 2.5 mg was superior to finasteride at both 12 and 24 weeks, and dutasteride raised target-area hair count versus placebo in a dose-dependent way [2]. The 2.5 mg result does not establish a 12-week result for 0.5 mg. Both trials stopped at 24 weeks [3][2].

Side effects across the first three months

The label notes that sexual reaction rates fell after the first 6 months, while breast disorders did not [1]. When dutasteride is taken with tamsulosin, the combination trial's figures for months 0 to 6 differ: ejaculation disorders 7.8% on the combination versus 1.0% on dutasteride alone and 2.2% on tamsulosin alone, impotence 5.4% versus 4.0% and 2.6%, decreased libido 4.5% versus 3.1% and 2.0%, and dizziness 1.1% versus 0.5% and 0.9% [1]. Trial withdrawal for adverse reactions was 6% on the combination versus 4% on either single drug, most often for erectile dysfunction (1% to 1.5%) [1].

Postmarketing reports listed in the Avodart label include hypersensitivity reactions (rash, itching, hives, localized edema, serious skin reactions, angioedema), male breast cancer, depressed mood, and testicular pain and swelling [1]. A Swedish register cohort of 2.2 million men aged 50 to 90 found that the 8,774 men who started dutasteride had a depression hazard ratio of 1.68 (95% CI 1.43 to 1.96) and no association with suicide (HR 0.98, 95% CI 0.62 to 1.54); it is observational and mostly older men treated for BPH [5].

Label items that matter early

• Blood donation: the label says men treated with Avodart should not donate blood until at least 6 months after the last dose, to prevent giving dutasteride to a pregnant transfusion recipient; serum levels stay above 0.1 ng/mL for up to 4 to 6 months after stopping [1].
• Handling: the label says women who are or may be pregnant should not handle Avodart capsules, because dutasteride can be absorbed through the skin and could harm a male fetus. It instructs that the contact area be washed immediately with soap and water after contact with a leaking capsule [1].
• Semen: in healthy men over 52 weeks, dutasteride reduced total sperm count by 23%, semen volume by 26% and sperm motility by 18% (placebo-adjusted); concentration and morphology were unaffected and all mean values stayed in the normal range; 24 weeks after stopping, total sperm count was still 23% below baseline, and the clinical significance for an individual's fertility is not known [1].
• High-grade prostate cancer: the label warns that 5-alpha reductase inhibitors may increase the risk of high-grade prostate cancer, with Gleason 8 to 10 cancer in 1.0% of men on Avodart versus 0.5% on placebo in the 4-year REDUCE trial [1][6].