Avodart (Dutasteride) in Geriatric Patients (65+): Transition to Adult Care

Does the dose change after 65?

No. The Avodart label gives a single regimen: 0.5 mg once daily, swallowed whole, with or without food. The label says the capsules should not be chewed or opened because contact with the contents may irritate the mouth and throat [1]. When it is used with tamsulosin, the doses are dutasteride 0.5 mg plus tamsulosin 0.4 mg, each once daily [1].

Dutasteride is a 5-alpha reductase inhibitor approved for symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate, to improve symptoms, reduce the risk of acute urinary retention (AUR) and reduce the risk of BPH-related surgery [1]. It is not approved for the prevention of prostate cancer [1].

The pooled trials behind the label enrolled men aged 47 to 94 with a mean age of 66 [1].

The first thing a new care team can get wrong: PSA

The label states that dutasteride reduces serum PSA by approximately 50% within 3 to 6 months, that the drop is predictable across the PSA range but can vary between individuals, and that the drug can lower PSA even when prostate cancer is present [1]. It directs a new baseline at least 3 months after starting, with periodic monitoring after that [1]. For an isolated value in a man treated 3 months or longer, the label says to double it before comparing with ranges for untreated men [1]. Any confirmed increase from the lowest on-treatment value may signal prostate cancer and should be evaluated even if it sits inside the normal range for untreated men [1]. Percent free PSA stays constant and needs no adjustment, and co-administration with tamsulosin changes PSA the same way dutasteride alone does [1]. The label also notes that noncompliance can affect PSA results [1].

A hospital, a new primary care practice or a long-term care facility that receives a PSA number without the note that the man takes dutasteride cannot apply these rules [1].

The 5-week half-life travels with the patient

The terminal half-life is about 5 weeks at steady state, with 65% of steady state reached after 1 month and about 90% after 3 months [1]. Serum levels stay above 0.1 ng/mL for up to 4 to 6 months after the last dose [1].

The Avodart label says men being treated with Avodart should not donate blood until at least 6 months have passed since the last dose, to prevent giving dutasteride to a pregnant transfusion recipient [1].

What the record needs besides the drug name

High-grade prostate cancer warning. The label warns that 5-alpha reductase inhibitors may increase the risk of high-grade prostate cancer [1]. In the 4-year REDUCE trial of men 50 to 75 with a prior negative biopsy and a PSA of 2.5 to 10 ng/mL, Gleason 8 to 10 cancer was found in 1.0% of men on Avodart versus 0.5% on placebo [1]. Among 6,729 men who underwent biopsy or prostate surgery, cancer was detected in 659 of 3,305 men in the dutasteride group versus 858 of 3,424 in the placebo group, a relative risk reduction of 22.8% (95% CI 15.2 to 29.8); in years 3 and 4 there were 12 Gleason 8 to 10 tumors on dutasteride versus 1 on placebo (P=0.003) [2]. Dutasteride is not approved for cancer prevention [1].

Other medications. Verapamil and diltiazem decrease dutasteride clearance and raise exposure, a change the label does not consider clinically significant and which needs no dose adjustment [1]. The effect of potent CYP3A4 inhibitors has not been studied, and the label advises caution with potent, chronic inhibitors such as ritonavir [1]. Dutasteride does not alter the steady-state pharmacokinetics of tamsulosin or terazosin, and it does not change digoxin or warfarin pharmacokinetics or warfarin's effect on prothrombin time [1].

Why it was started. In CombAT, combination therapy with tamsulosin was superior to tamsulosin alone but not to dutasteride alone for reducing AUR or BPH-related surgery at 4 years, and superior to either alone for symptoms and clinical progression [3].

What the BPH trials found

The three pooled two-year BPH trials enrolled 4,325 men and found a mean reduction in total prostate volume of 25.7% at 24 months, an AUA symptom score improvement of 4.5 points (21.4%), a 57% reduction in the risk of acute urinary retention and a 48% reduction in the risk of BPH-related surgery compared with placebo; symptom scores improved as early as 3 months [4].

CombAT randomized 4,844 men aged 50 and older to dutasteride, tamsulosin, or both for 4 years [3]. According to the Avodart label, mean symptom score change at month 24 was -6.2 with combination therapy, -4.9 with dutasteride and -4.3 with tamsulosin, and mean prostate volume fell 26.9%, 28.0% and 0% respectively [1]. These figures are for the whole enrolled population, whose mean age was 66 [1].

Side effects the label reports

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

Postmarketing reports in the Avodart label include male breast cancer, depressed mood, and testicular pain and swelling; the label lists depressed mood but not suicidal ideation [1]. A Swedish register cohort of 2.2 million men aged 50 to 90, which included 8,774 men who started dutasteride, found a depression hazard ratio of 1.68 (95% CI 1.43 to 1.96) that was constant over time, and no association with suicide (HR 0.98, 95% CI 0.62 to 1.54) [5]. It is an observational study of mostly older men with BPH [5].

Cardiac failure (a composite term) was numerically higher with combination therapy in CombAT (0.7%, 12 of 1,610) than with dutasteride alone (0.1%, 2 of 1,623) or tamsulosin alone (0.6%, 9 of 1,611), and 0.6% (26 of 4,105) versus 0.4% (15 of 4,126) on placebo in REDUCE; the label states that the clinical significance is unknown and that no causal relationship has been established [1].

What to carry across a handoff

For a man on dutasteride moving between practices or facilities, the useful details are the 0.5 mg dose, whether it is taken alone or with tamsulosin 0.4 mg, and, if it was stopped, the date of the last dose, since the label's 6-month blood donation deferral counts from that date [1]. For PSA, the label's interpretation rules rely on the on-treatment baseline set at least 3 months after starting and the lowest on-treatment value, so those results are worth passing along with the pre-treatment value [1]. The label's interaction section names verapamil, diltiazem and potent, chronic CYP3A4 inhibitors such as ritonavir [1].

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