Introduction
Dutasteride is a synthetic 4-azasteroid compound that acts as a competitive and specific inhibitor of both type 1 and type 2 5α-reductase isoenzymes. Marketed under the brand name Avodart among others, it is primarily used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate. Unlike finasteride, which selectively inhibits only type 2 5α-reductase, dutasteride's dual inhibition provides more complete suppression of dihydrotestosterone (DHT) production.
Mechanism of Action
Dutasteride works by inhibiting both type 1 and type 2 isoforms of 5α-reductase, the intracellular enzymes that convert testosterone to the more potent androgen DHT. Type 1 5α-reductase is predominantly found in the skin, liver, and prostate, while type 2 is primarily located in the prostate, seminal vesicles, and hair follicles. By blocking the conversion of testosterone to DHT, dutasteride significantly reduces serum and intraprostatic DHT levels by up to 90-94% within 1-2 weeks of therapy. This reduction in DHT leads to decreased prostate volume, improved urinary flow, and reduced risk of acute urinary retention and BPH-related surgery.
Indications
- Treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate
- Used as combination therapy with tamsulosin for BPH (marketed as Combodart/Jalyn)
- Off-label use for androgenetic alopecia (male pattern baldness), though not FDA-approved for this indication
Dosage and Administration
Standard adult dosage: 0.5 mg orally once daily Administration: Can be taken with or without food Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Use with caution in patients with severe liver disease
- Geriatric patients: No dosage adjustment required
- Women and children: Contraindicated
Treatment response for BPH may require 3-6 months of therapy. Capsules should not be handled by women who are or may become pregnant due to risk of absorption through skin.
Pharmacokinetics
Absorption: Absolute bioavailability approximately 60% (range 40-94%). Food does not affect absorption. Distribution: Volume of distribution ~300-500 L. Highly bound to plasma proteins (>99%). Metabolism: Extensively metabolized by CYP3A4 to three major metabolites. Elimination: Terminal half-life approximately 5 weeks. Excretion primarily via feces (∼40%) with lesser amounts in urine (∼5%). Steady-state: Achieved after 4-6 months of daily dosing due to long half-life.Contraindications
- Hypersensitivity to dutasteride, other 5α-reductase inhibitors, or any component of the formulation
- Use in women
- Use in children
- Pregnancy (Category X) - may cause fetal harm
Warnings and Precautions
- Pregnancy warning: Women who are or may become pregnant should not handle crushed or broken tablets due to risk of absorption through skin and potential fetal harm
- Prostate cancer risk: May increase risk of high-grade prostate cancer; patients should be evaluated to rule out prostate cancer before initiating therapy
- Blood donation: Patients should not donate blood until at least 6 months after last dose to prevent administration to pregnant women
- Hepatic impairment: Use with caution in patients with severe liver disease
- Depression: Monitor for mood changes including depression
- Sexual function: May cause decreased libido, erectile dysfunction, and ejaculation disorders
Drug Interactions
- Potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin): May increase dutasteride concentrations
- Alpha-blockers (e.g., tamsulosin): No clinically significant interactions noted
- Warfarin: No significant interaction observed
- Other 5α-reductase inhibitors: Concomitant use not recommended
Adverse Effects
Common (≥1%):- Erectile dysfunction (4.7-7.3%)
- Decreased libido (3.0-4.2%)
- Ejaculation disorders (1.4-2.2%)
- Gynecomastia (0.5-2.2%)
- Testicular pain
- Dizziness
- Allergic reactions including rash, pruritus, urticaria, and angioedema
- High-grade prostate cancer
- Depression
- Male infertility
Monitoring Parameters
- Prostate-specific antigen (PSA) levels: Baseline and periodically (PSA decreases by approximately 50% after 6 months of therapy)
- Prostate examination: Digital rectal exam at baseline and periodically
- Liver function tests: In patients with hepatic impairment
- Symptom assessment: International Prostate Symptom Score (IPSS) and urinary flow rates
- Monitoring for sexual side effects and mood changes
- Regular follow-up for prostate cancer screening
Patient Education
- Take medication exactly as prescribed; do not crush or break capsules
- Women who are or may become pregnant should not handle the medication
- Results may take 3-6 months to become apparent
- Report any breast changes, lumps, pain, or nipple discharge promptly
- Be aware of potential sexual side effects
- Do not donate blood while taking this medication and for at least 6 months after stopping
- Continue regular prostate cancer screenings as recommended by your physician
- Inform all healthcare providers about dutasteride use, especially if undergoing PSA testing
References
1. FDA Prescribing Information: Avodart (dutasteride) capsules 2. Boyle P, Gould AL, Roehrborn CG. Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology. 1996;48(3):398-405. 3. Roehrborn CG, 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. 4. Clark RV, et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004;89(5):2179-2184. 5. Andriole GL, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362(13):1192-1202. 6. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2023. Dutasteride. 7. Micromedex Solutions [Internet]. Greenwood Village (CO): Truven Health Analytics; 2023. Dutasteride.