Avodart FDA Approval History: Complete Regulatory Timeline for Dutasteride

What exactly did the FDA approve on November 20, 2001?

The original approval for Avodart is dated November 20, 2001, under NDA 021319. Drugs@FDA records it as a type 1 new molecular entity reviewed on the standard track, marketed as a prescription-only 0.5 mg soft gelatin capsule [1]. The indication the current label carries is symptomatic benign prostatic hyperplasia in men with an enlarged prostate, to improve symptoms, reduce the risk of acute urinary retention and reduce the risk of BPH-related surgery [2].

The label's limitations section adds a line that still matters to anyone reading the approval record: Avodart is not approved for the prevention of prostate cancer [2]. The application is now held by Waylis Therapeutics [1], and the current prescribing information is effective March 12, 2025 [2].

Three identical trials in men with BPH

Three identical 2-year placebo-controlled trials enrolled 4,325 men with moderate to severe symptoms, a prostate volume of 30 cm3 or more and a PSA of 1.5 to 10 ng/mL [3]. At 24 months, serum dihydrotestosterone had fallen by a mean of 90.2%, total prostate volume by 25.7% and transition zone volume by 20.4%; the symptom score improved by 4.5 points (21.4%) and peak urinary flow rose by 2.2 mL/s [3]. Compared with placebo, the risk of acute urinary retention fell by 57% and the risk of BPH-related surgery by 48% over those 24 months [3].

Dutasteride inhibits both the type 1 and type 2 forms of 5-alpha-reductase and does not bind the androgen receptor [2]. In a 24-week dose-ranging study of 399 men with BPH, dutasteride 0.5 mg lowered serum DHT by a mean of 94.7% versus 70.8% with finasteride 5 mg [4]. The label's own figures: median serum DHT down 85% after 1 week and 90% after 2 weeks at 0.5 mg daily, 94% at 1 year and 95% at 3 and 4 years, with median testosterone up roughly 19% to 26% but still inside the physiologic range [2].

What does the supplement record for NDA 021319 show?

Drugs@FDA lists supplements to the application by action date and category [1]. Selected entries:

What does the Avodart label say about combining with tamsulosin?

The Avodart label carries a combination indication: Avodart with the alpha-adrenergic antagonist tamsulosin for the treatment of symptomatic BPH in men with an enlarged prostate, dosed as dutasteride 0.5 mg once daily plus tamsulosin 0.4 mg once daily [2].

The supporting trial, CombAT, randomized 4,844 men aged 50 or older with an IPSS of 12 or more, prostate volume of 30 cm3 or more and PSA of 1.5 to 10 ng/mL to dutasteride, tamsulosin or both for 4 years, with no placebo arm [5]. Combination therapy was superior to tamsulosin alone but not to dutasteride alone at reducing the relative risk of acute urinary retention or BPH-related surgery, and was superior to both monotherapies for BPH clinical progression and symptoms [5].

What did the REDUCE trial change in the label?

REDUCE randomized 8,231 men aged 50 to 75 with a PSA of 2.5 to 10 ng/mL and a negative biopsy to dutasteride 0.5 mg (4,105 men) or placebo (4,126 men) for up to 4 years [2]. Among the 6,729 men who had a biopsy or prostate surgery, cancer was detected in 659 of 3,305 on dutasteride and 858 of 3,424 on placebo, a relative risk reduction of 22.8% (95% CI 15.2 to 29.8) [6].

Gleason 7 to 10 tumors over years 1 to 4 numbered 220 on dutasteride versus 233 on placebo (P=0.81). In years 3 and 4 alone there were 12 Gleason 8 to 10 tumors on dutasteride versus 1 on placebo (P=0.003) [6]. The current label reports the Gleason 8 to 10 rate as 1.0% on Avodart versus 0.5% on placebo and states that 5-alpha reductase inhibitors may increase the risk of development of high-grade prostate cancer [2]. The label also notes that whether the drugs' effect of reducing prostate volume or trial-related factors influenced these results has not been established, and cites a similar finding in a 7-year finasteride 5 mg trial (1.8% versus 1.1%) [2]. Acute urinary retention in REDUCE was 1.6% on dutasteride versus 6.7% on placebo [6]. The prevention of prostate cancer remains outside the approved indication [2].

What does the current Avodart label warn about?

The current Avodart label includes warnings and precautions about high-grade prostate cancer, PSA interpretation, pregnancy exposure and blood donation [2].

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

Sexual and breast adverse reactions. In the pooled 2-year placebo-controlled BPH trials (2,167 men on Avodart, 2,158 on placebo, mean age 66), during months 0 to 6 impotence was reported 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 in 0.5% versus 0.2% [2]. Rates fell after the first 6 months except breast disorders, which were 1.1% versus 0.3% at months 13 to 18. The label notes that these sexual adverse reactions may persist after discontinuation and that the role of dutasteride in that persistence is unknown [2]. Postmarketing reports listed in the label include hypersensitivity reactions (rash, itching, hives, localized edema, serious skin reactions, angioedema), male breast cancer, depressed mood, and testicular pain and swelling [2].

PSA handling. Dutasteride lowers serum PSA by about 50% within 3 to 6 months. The label says to establish a new PSA baseline at least 3 months after starting and, for an isolated value in a man treated 3 months or more, to double it for comparison with untreated men; any confirmed rise from the lowest on-treatment value may signal prostate cancer and should be evaluated even if still within the normal range. Percent free PSA is unchanged, and giving tamsulosin alongside dutasteride changes PSA the same way as dutasteride alone [2].

Blood donation and pregnancy. The label says men being 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 detectable (above 0.1 ng/mL) for up to 4 to 6 months after stopping, with a terminal half-life of about 5 weeks [2]. The label contraindicates use in pregnancy. It says women who are or may be pregnant should not handle the capsules, since 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 area immediately with soap and water [2]. The other contraindication is previous clinically significant hypersensitivity, such as serious skin reactions or angioedema, to Avodart or another 5-alpha reductase inhibitor [2].

What has the FDA not approved dutasteride for?

Hair loss. Avodart carries no FDA approval for androgenetic alopecia, and use for hair loss in the United States is off-label [2]. One randomized study of that use assigned 917 men aged 20 to 50 with androgenetic alopecia to dutasteride 0.02, 0.1 or 0.5 mg daily, finasteride 1 mg daily or placebo for 24 weeks; dutasteride 0.5 mg increased hair count more than finasteride (P=.003) and placebo (P<.001), with similar numbers and severity of adverse events across groups [7]. A meta-analysis of 15 placebo-controlled trials covering 4,495 men found a 1.57-fold relative risk of sexual dysfunction across 5-alpha reductase inhibitors, 1.66 for finasteride 1 mg and 1.37 (95% CI 0.81 to 2.32, not statistically significant) for dutasteride 0.5 mg, with few dutasteride trials available [8].

Prostate cancer prevention is also outside the approval, despite the 22.8% relative reduction in biopsy-detected cancer in REDUCE and the label's warning about high-grade tumors [2][6].