What is the comparison between Finasteride (5-alpha-reductase inhibitor) and Dutasteride (5-alpha-reductase inhibitor)?

From the Guidelines

Dutasteride is generally more effective than finasteride in reducing DHT levels and improving symptoms of benign prostatic hyperplasia (BPH), with a reduction of approximately 95% in serum DHT levels compared to 70% with finasteride 1.

Key Differences Between Finasteride and Dutasteride

• Finasteride selectively inhibits the 5-AR type II isoenzyme, while dutasteride inhibits both types I and II, leading to a greater reduction in DHT levels 1.
• The reduction of DHT in prostate tissues has been measured at approximately 80% with finasteride and 94% with dutasteride 1.
• Dutasteride has been shown to be more effective in reducing the risk of clinical progression of BPH, including an increase in IPSS, AUR, UTI, or BPH-related surgery, compared to finasteride 1.

Clinical Implications

• Patients with larger prostates and/or higher PSA values may benefit more from dutasteride due to its greater potency and ability to reduce DHT levels 1.
• The PLESS study suggested that 5-ARI therapy, including dutasteride, can be utilized in appropriately enlarged prostates as prevention for BPH, altering the natural history of the disease 1.
• Clinicians should consider the differences in pharmacological activity and clinical efficacy between finasteride and dutasteride when selecting a treatment option for patients with BPH 1.

Important Considerations

• Both finasteride and dutasteride can cause similar side effects, including sexual dysfunction, decreased libido, and rarely, depression 1.
• Patients should be counseled on the slow onset of action of these medications and the potential need for long-term treatment to maintain benefits 1.

From the FDA Drug Label

1. 2 Increased Risk of High-Grade Prostate Cancer Men aged 55 and over with a normal digital rectal examination and PSA ≤3.0 ng/mL at baseline taking finasteride 5 mg/day in the 7-year Prostate Cancer Prevention Trial (PCPT) had an increased risk of Gleason score 8 to 10 prostate cancer (finasteride 1.8% vs placebo 1.1%). Similar results were observed in a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor (dutasteride, AVODART) (1% dutasteride vs 0. 5% placebo).

Comparison of Finasteride and Dutasteride:

• Both finasteride and dutasteride are 5α-reductase inhibitors.
• Both drugs have been associated with an increased risk of high-grade prostate cancer.
• The increased risk of high-grade prostate cancer with finasteride was 1.8% vs 1.1% with placebo in the PCPT trial.
• The increased risk of high-grade prostate cancer with dutasteride was 1% vs 0.5% with placebo in a 4-year placebo-controlled clinical trial. Key Points:
• Both finasteride and dutasteride may increase the risk of development of high-grade prostate cancer.
• The effect of 5α-reductase inhibitors to reduce prostate volume, or study-related factors, impacted the results of these studies has not been established 2.
• Similar results were observed with dutasteride in a separate clinical trial 3.

From the Research

Comparison of Finasteride and Dutasteride

• Finasteride and dutasteride are both used to treat androgenetic alopecia, with finasteride being FDA-approved and dutasteride being used off-label 4, 5.
• Dutasteride has been shown to be more effective than finasteride in several studies, with comparable adverse effects 4, 5, 6.
• The mechanism of action of finasteride and dutasteride differs, with finasteride inhibiting 5α-reductase type II isoenzyme and dutasteride inhibiting both type I and type II isoenzymes 5.

Efficacy and Safety

• Studies have shown that dutasteride has better efficacy than finasteride in treating androgenetic alopecia, with a probable efficacy ranking of dutasteride 0.5 mg/d, finasteride 5 mg/d, minoxidil 5 mg/d, finasteride 1 mg/d, followed by minoxidil 0.25 mg/d 5.
• The safety profiles of finasteride and dutasteride are similar, with common adverse effects including sexual dysfunction and neuropsychiatric side effects 5, 7.
• Finasteride has been associated with erectile dysfunction, although the evidence is not conclusive 7.

Administration and Formulation

• Dutasteride can be administered orally, with a plasma half-life of approximately 5 weeks 5.
• Mesotherapy with dutasteride and microneedling combined with dutasteride solution can reduce adverse events caused by oral medication and exhibit certain efficacy 6.
• Liposomes or nanoparticles of dutasteride are under development and may become an efficient topical formulation 6.