Finasteride - Drug Monograph

Introduction

Finasteride is a synthetic 4-azasteroid compound that functions as a specific, competitive inhibitor of Type II 5α-reductase, an intracellular enzyme that converts testosterone to the more potent androgen dihydrotestosterone (DHT). It is widely used in clinical practice for the treatment of benign prostatic hyperplasia (BPH) and androgenetic alopecia (male pattern hair loss).

Mechanism of Action

Finasteride exerts its therapeutic effects through selective inhibition of Type II 5α-reductase, the predominant isoenzyme found in the prostate gland, seminal vesicles, and hair follicles. By blocking the conversion of testosterone to DHT, finasteride significantly reduces serum and tissue DHT concentrations by approximately 70%. This reduction in DHT leads to decreased stimulation of androgen receptors in prostate tissue (resulting in reduced prostate volume) and hair follicles (promoting hair retention and regrowth).

Indications

• Benign Prostatic Hyperplasia (5 mg dose): Treatment of symptomatic BPH to improve symptoms, reduce the risk of acute urinary retention, and reduce the need for surgery
• Androgenetic Alopecia (1 mg dose): Treatment of male pattern hair loss in men only

Dosage and Administration

• Renal impairment: No dosage adjustment necessary
• Hepatic impairment: No dosage adjustment necessary, but caution advised in severe impairment
• Geriatric patients: No dosage adjustment necessary
• Pediatric patients: Not indicated for use in children
• Women: Contraindicated in women, particularly those who are or may become pregnant

Pharmacokinetics

• Absorption: Bioavailability approximately 80%, not significantly affected by food
• Distribution: Volume of distribution 76 L, extensively bound to plasma proteins (approximately 90%)
• Metabolism: Extensively metabolized in the liver via cytochrome P450 3A4
• Elimination: Terminal half-life approximately 6-8 hours; excreted in feces (57%) and urine (39%)
• Steady-state: Achieved within 24 hours; DHT suppression maintained with once-daily dosing

Contraindications

• Hypersensitivity to finasteride or any component of the formulation
• Use in women, particularly pregnant women or women who may become pregnant (due to risk of fetal abnormalities)
• Use in pediatric patients

Warnings and Precautions

• Pregnancy exposure risk: Women who are or may become pregnant should not handle crushed or broken tablets due to risk of absorption and potential fetal harm
• Prostate cancer: May increase risk of high-grade prostate cancer; patients should be appropriately evaluated prior to initiating therapy and monitored during treatment
• Effects on PSA: Reduces serum PSA concentrations by approximately 50% after 6 months of treatment; PSA values should be doubled for comparison to normal ranges in untreated men
• Depression: Postmarketing reports of depression and suicidal ideation; monitor for mood changes
• Sexual dysfunction: May cause decreased libido, erectile dysfunction, and ejaculation disorders

Drug Interactions

• Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): May increase finasteride concentrations
• 5α-reductase inhibitors: Avoid concomitant use with other 5α-reductase inhibitors (e.g., dutasteride)
• Herbal supplements: Saw palmetto may have additive effects

Adverse Effects

• Decreased libido (3.4-3.8%)
• Erectile dysfunction (4.9-8.1%)
• Ejaculation disorders (2.2-3.7%)
• Gynecomastia (2.2%)

• Depression
• Skin rash
• Testicular pain
• Breast tenderness

• Allergic reactions including lip swelling
• Male breast cancer
• Suicidal ideation

Monitoring Parameters

• BPH patients: Symptom score (IPSS), urinary flow rate, prostate volume, PSA (with appropriate interpretation)
• Sexual function: Baseline and periodic assessment of libido and sexual function
• Mood: Monitor for depression or changes in mood
• Breast changes: Regular breast examination for tenderness or masses
• Prostate cancer screening: Appropriate monitoring as clinically indicated

Patient Education

• Take medication exactly as prescribed; do not crush or break tablets
• Women who are pregnant or may become pregnant should not handle crushed or broken tablets
• Results for hair loss may take 3-6 months to become apparent; continued use is necessary to maintain benefits
• Be aware of potential sexual side effects and discuss any concerns with your healthcare provider
• Regular follow-up appointments are important for monitoring effectiveness and safety
• Inform all healthcare providers about finasteride use, especially when having PSA tests
• Report any breast changes, testicular pain, or mood changes promptly

References

1. Roehrborn CG, Boyle P, Nickel JC, et al. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology. 2002;60(3):434-441. 2. Kaufman KD, Olsen EA, Whiting D, et al. Finasteride in the treatment of men with androgenetic alopecia. J Am Acad Dermatol. 1998;39(4 Pt 1):578-589. 3. FDA Prescribing Information: Proscar (finasteride) and Propecia (finasteride). 4. Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003;349(3):215-224. 5. Hirshburg JM, Kelsey PA, Therrien CA, et al. Adverse effects and safety of 5-alpha reductase inhibitors (finasteride, dutasteride): a systematic review. J Clin Aesthet Dermatol. 2016;9(7):56-62. 6. Zito PM, Bistas KG, Syed K. Finasteride. [Updated 2023 Aug 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.