Avodart (Dutasteride) After Bariatric Surgery: What Patients and Clinicians Need to Know

Is there any evidence on dutasteride specifically after bariatric surgery?

Dutasteride-specific data after bariatric surgery are not established. The closest evidence is a systematic review of drug absorption after weight-loss surgery that covered 26 studies, including 15 case reports or case series and 11 non-randomized controlled studies [2].

In that review, diminished absorption was most consistently reported for cyclosporine, thyroxine, phenytoin and rifampin, and the effect of surgery was drug-specific rather than uniform. The authors noted that drugs that are intrinsically poorly absorbed, highly lipophilic, or subject to enterohepatic recirculation had the greatest potential for malabsorption, and they called for controlled studies of modern procedures [2].

Avodart's label reports an absolute bioavailability of about 60% [1]. Whether bariatric surgery changes dutasteride exposure enough to matter is unknown.

What the label says about absorption

Dutasteride 0.5 mg capsules reach peak serum concentration in 2 to 3 hours and have an absolute bioavailability of about 60% [1]. Food lowers the peak concentration by 10 to 15%, a change the label does not consider clinically significant, and the capsule may be taken with or without food [1]. The drug is 99.0% bound to albumin and 96.6% to alpha-1 acid glycoprotein, has a volume of distribution of 300 to 500 L, and is metabolized by CYP3A4 and CYP3A5 [1]. At steady state the terminal half-life is about 5 weeks; the label notes that 65% of steady state is reached after 1 month and about 90% after 3 months, and that serum levels stay detectable above 0.1 ng/mL for up to 4 to 6 months after the last dose [1].

Can the capsule be opened, crushed or split after surgery?

The label says the capsule should be swallowed whole and not chewed or opened, because contact with the contents may irritate the lining of the mouth and throat [1]. The label does not provide an alternative way to take the capsule if swallowing it whole is difficult [1]. It does allow the capsule with or without food [1].

Does the long half-life change anything?

The label gives one concrete rule tied to slow elimination: men being treated with Avodart should not donate blood until at least 6 months have passed since the last dose, to prevent a pregnant transfusion recipient from receiving dutasteride [1]. The label's explanation is that serum levels remain above 0.1 ng/mL for up to 4 to 6 months after stopping, with a terminal half-life of about 5 weeks [1].

The label does not provide instructions for handling a missed dose. It does state that noncompliance can affect PSA test results [1].

PSA on dutasteride: how the label rule works

Avodart lowers serum PSA by about 50% within 3 to 6 months of treatment [1]. The label's instructions are specific: establish a new PSA baseline at least 3 months after starting, monitor periodically after that, and double an isolated PSA value in a man who has taken dutasteride for 3 months or more when comparing it with normal ranges for untreated men [1]. Any confirmed increase from the lowest value on treatment may signal prostate cancer and should be evaluated even if the number is still within the normal range for untreated men [1]. Percent free PSA stays constant, and the label says no adjustment appears necessary [1]. Adding tamsulosin changes PSA the same way as dutasteride alone [1].

Interactions listed in the label

Dutasteride is extensively metabolized by CYP3A4 and CYP3A5, and the effect of potent CYP3A4 inhibitors on dutasteride has not been studied; the label advises caution with potent, chronic CYP3A4 inhibitors such as ritonavir [1]. Verapamil and diltiazem decrease dutasteride clearance and raise exposure, a change the label does not consider clinically significant, with no dose adjustment recommended [1]. A single 5 mg dose of Avodart followed an hour later by 12 g of cholestyramine did not affect dutasteride bioavailability [1]. Dutasteride does not alter the steady-state pharmacokinetics of tamsulosin or terazosin, digoxin, or warfarin, and it does not change warfarin's effect on prothrombin time [1].

Hair loss use, which is off-label

Avodart is not FDA-approved for hair loss; the only approved use is symptomatic BPH in men with an enlarged prostate, alone or with tamsulosin [1].

In a 24-week randomized trial of 917 men aged 20 to 50 with androgenetic alopecia, dutasteride 0.5 mg daily increased hair count and hair width more than finasteride 1 mg daily (P=.003 for hair count) and more than placebo (P<.001 for all three measures), with a similar number and severity of adverse events across groups [3]. A separate randomized trial of 153 men compared dutasteride 0.5 mg with placebo for 6 months and found hair count rose 12.2 per cm2 versus 4.7 per cm2 (P=.0319) [4]. A 2019 meta-analysis of 15 placebo-controlled trials (4,495 men) found a 1.57-fold overall relative risk of sexual dysfunction with 5-alpha reductase inhibitors; for dutasteride 0.5 mg 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 [5]. Both hair-loss trials were short, and both enrolled men with androgenetic alopecia, not post-bariatric patients.

What to watch for

In pooled two-year placebo-controlled BPH trials (2,167 men on Avodart, 2,158 on placebo, mean age 66), the rates over the first 6 months 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 6 months except for breast disorders, and the label notes that these sexual reactions may persist after stopping, with the role of dutasteride in that persistence unknown [1]. Postmarketing reports listed in the label include male breast cancer, depressed mood, and testicular pain and swelling [1].

On semen, over 52 weeks dutasteride reduced total sperm count by 23%, semen volume by 26% and sperm motility by 18% compared with placebo; concentration and morphology were unaffected and mean values stayed within the normal range, total sperm count was still 23% below baseline 24 weeks after stopping, and the clinical significance for an individual man's fertility is not known [1].

On prostate cancer, the label states that 5-alpha reductase inhibitors may increase the risk of high-grade prostate cancer; in the 4-year REDUCE trial, Gleason 8 to 10 cancer was found in 1.0% of men on Avodart versus 0.5% on placebo [1]. Dutasteride is not approved for prostate cancer prevention [1].

The label says 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 area should be washed immediately with soap and water [1].

A Swedish register cohort of 2.2 million men aged 50 to 90 found that dutasteride starters had a higher hazard of depression (HR 1.68, 95% CI 1.43 to 1.96) with no association with suicide (HR 0.98, 95% CI 0.62 to 1.54); the study was observational and most men had BPH [6].