Avodart Workplace Considerations: Living and Working With Dutasteride

Which workplace issues are real

Avodart is dutasteride 0.5 mg in a soft gelatin capsule, a prescription 5-alpha-reductase inhibitor approved for symptomatic benign prostatic hyperplasia in men with an enlarged prostate, alone or with tamsulosin [2][1]. It is not approved to prevent prostate cancer, and hair-loss use is off-label [1].

Four label facts matter most for a working life on dutasteride: PSA falls by about half, women who are pregnant or may be pregnant should not handle the capsules, blood donation is deferred for 6 months after the last dose, and the drug clears slowly, with a terminal half-life of about 5 weeks [1].

The PSA problem at an occupational health screening

Dutasteride lowers serum PSA by approximately 50% within 3 to 6 months of starting [1]. This matters for anyone whose job involves a company physical, a fitness-for-duty panel or an insurance blood draw.

The label says a new PSA baseline should be established at least 3 months after starting treatment, and that an isolated PSA value in a man treated for 3 months or more should be doubled for comparison with normal values in untreated men [1]. Any confirmed increase from the lowest PSA value while on treatment may signal prostate cancer and should be evaluated even if the number is still within the normal range [1]. Percent free PSA remains constant and needs no adjustment [1]. Adding tamsulosin changes PSA the same way dutasteride alone does [1], and the label notes that non-compliance can also affect PSA results [1].

Dizziness and safety-sensitive work

Dizziness is the listed reaction most relevant to driving or machinery work. In the first six months of CombAT it was reported by 0.5% of men on dutasteride alone, 1.1% on dutasteride plus tamsulosin and 0.9% on tamsulosin alone [1].

In the pooled 2-year monotherapy trials, 4% of men on dutasteride and 3% on placebo withdrew because of adverse reactions, most commonly impotence at 1% [1]. In CombAT, withdrawal for adverse reactions was 6% on combination therapy versus 4% on either monotherapy, with erectile dysfunction the most common reason at 1% to 1.5% [1].

Pregnant coworkers and capsule handling

Women who are pregnant or may be pregnant should not handle Avodart capsules, because dutasteride can be absorbed through the skin and could harm a male fetus; if a pregnant woman touches a leaking capsule, the label says to wash the contact area immediately with soap and water [1]. Pregnancy is a contraindication, and in animal studies dutasteride inhibited development of the male fetus's external genitalia [1].

For a pregnant partner, the label gives a human exposure estimate: the highest measured semen concentration was 14 ng/mL, and a 50-kg woman exposed to 5 mL of semen with complete absorption would have an expected blood concentration of about 0.0175 ng/mL, roughly 100 times less than blood concentrations that produced abnormalities of male genitalia in animal studies [1].

Sexual side effects: what the label counts

In the pooled 2-year placebo-controlled BPH trials (2,167 men on Avodart, 2,158 on placebo, mean age 66), months 0 to 6 brought impotence in 4.7% versus 1.7%, decreased libido in 3.0% versus 1.4%, ejaculation disorders in 1.4% versus 0.5%, and breast disorders such as enlargement or tenderness in 0.5% versus 0.2% [1]. Rates fell after the first 6 months except breast disorders, which were 1.1% versus 0.3% at months 13 to 18 [1]. The label notes these sexual reactions may persist after stopping and that the role of dutasteride in that persistence is unknown [1].

For a younger man taking dutasteride for hair loss rather than BPH, a 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; for dutasteride 0.5 mg specifically 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 [3].

Fertility and semen changes

In healthy men treated for 52 weeks, dutasteride reduced total sperm count by 23%, semen volume by 26% and sperm motility by 18% compared with placebo [1]. Sperm concentration and morphology were unaffected, mean values for all semen parameters stayed within the normal range, and after 24 weeks off treatment total sperm count was still 23% below baseline [1]. The label states that the clinical significance of these changes for an individual man's fertility is not known [1].

Blood donation: the six-month rule

Men treated with Avodart should not donate blood until at least 6 months after their last dose, to prevent giving dutasteride to a pregnant transfusion recipient [1]. Serum levels stay detectable above 0.1 ng/mL for up to 4 to 6 months after stopping, and the terminal half-life is about 5 weeks [1].

Fitting the dose around a workday

Avodart is taken as 0.5 mg once daily, swallowed whole and not chewed or opened, since contact with the capsule contents may irritate the mouth and throat, with or without food [1]. The dosing section gives no time of day [1].

Blood levels move slowly. The terminal half-life is about 5 weeks, with 65% of steady state reached after 1 month and about 90% after 3 months [1]. Peak concentration arrives 2 to 3 hours after a dose, and food lowers the peak by 10% to 15%, which the label calls not clinically significant [1].

Off-label use for hair loss

A 24-week randomized trial of 917 men aged 20 to 50 with androgenetic alopecia found that dutasteride 0.5 mg daily increased hair count more than finasteride 1 mg (P=.003) and more than placebo (P<.001) [4]. The number and severity of adverse events were similar across the treatment groups, and the study was limited to 24 weeks [4].

Drug interactions that could come up at work

Dutasteride is extensively metabolized by CYP3A4 and CYP3A5 [1]. The label advises caution with potent, chronic CYP3A4 inhibitors such as ritonavir; the effect of those inhibitors on dutasteride has not been studied [1]. Verapamil and diltiazem decrease dutasteride clearance and increase exposure, which the label does not consider clinically significant and for which no dose adjustment is recommended [1]. Dutasteride does not change the steady-state pharmacokinetics of tamsulosin or terazosin, does not alter digoxin or warfarin pharmacokinetics or warfarin's effect on prothrombin time, and its bioavailability is unchanged by cholestyramine [1].