Drug Monograph
Dutasteride (Avodart)
dutasteride
Pharmacokinetic Profile
Half-Life
~5 weeks (steady state)
Metabolism
CYP3A4, CYP3A5
Protein Binding
99.0% (albumin), 96.6% (AAG)
Bioavailability
~60% (range 40–94%)
Volume of Distribution
300–500 L
Clinical Information
Drug Class
Dual 5α-Reductase Inhibitor
Available Doses
0.5 mg soft gelatin capsule
Route
Oral
Renal Adjustment
None required
Hepatic Adjustment
Not studied; use caution
Pregnancy
Contraindicated
Lactation
Not indicated in women
Schedule / Legal Status
Prescription only (not scheduled)
Generic Available
Yes (since 2015)
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Symptomatic BPH — symptom improvement | Adult males with enlarged prostate | Monotherapy | FDA Approved |
| BPH — reduction of acute urinary retention risk | Adult males with enlarged prostate | Monotherapy | FDA Approved |
| BPH — reduction of need for surgical intervention | Adult males with enlarged prostate | Monotherapy | FDA Approved |
| Symptomatic BPH — combination therapy | Adult males with enlarged prostate | Combination with tamsulosin 0.4 mg | FDA Approved |
Dutasteride is a cornerstone treatment for men with symptomatic benign prostatic hyperplasia (BPH) and an enlarged prostate gland. In pivotal trials involving over 4,300 men, dutasteride reduced prostate volume by approximately 25% at one year and reduced the combined risk of acute urinary retention and BPH-related surgery by roughly 50% relative to placebo over two years (FDA PI). The combination of dutasteride with the alpha-blocker tamsulosin, evaluated in the four-year CombAT trial, provides superior symptom improvement compared with either agent alone. Dutasteride is explicitly not approved for prostate cancer prevention (FDA PI).
Off-Label Uses
Male androgenetic alopecia (AGA): Dutasteride 0.5 mg daily is approved for AGA in South Korea, Japan, and Taiwan. In the US it is widely used off-label. A phase III dose-ranging trial (Gubelin Harcha et al., JAAD 2014) demonstrated that dutasteride 0.5 mg daily produced significantly greater increases in hair count and width than finasteride 1 mg daily at 24 weeks. Evidence quality: Moderate
Hirsutism in women (theoretical): As a dual 5-alpha-reductase inhibitor, dutasteride could theoretically be more potent than finasteride for this indication, but clinical evidence is lacking and the drug is teratogenic. Evidence quality: Very low
Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| BPH — monotherapy, symptom relief and disease modification | 0.5 mg once daily | 0.5 mg once daily | 0.5 mg/day | Swallow capsule whole; may take with or without food Symptom improvement may require 3–6 months; maximum effect on prostate volume at 6–12 months |
| BPH — combination with alpha-blocker (tamsulosin) | 0.5 mg + tamsulosin 0.4 mg daily | 0.5 mg + tamsulosin 0.4 mg daily | 0.5 mg/day | CombAT trial showed superior symptom improvement vs. monotherapy at 2 years Available as fixed-dose combination (Jalyn) |
| Male androgenetic alopecia (off-label) | 0.5 mg once daily | 0.5 mg once daily | 0.5 mg/day | FDA-approved in South Korea, Japan, Taiwan at this dose Improvement typically assessed at 24 weeks; superior to finasteride 1 mg in pivotal trial |
| Elderly patients (≥65 years) | 0.5 mg once daily | 0.5 mg once daily | 0.5 mg/day | No dose adjustment needed Half-life is age-dependent: ~170 h (20–49 y), ~260 h (50–69 y), ~300 h (>70 y) |
| Renal impairment | 0.5 mg once daily | 0.5 mg once daily | 0.5 mg/day | No dose adjustment; <0.1% excreted renally Applicable across all severities of renal impairment |
| Hepatic impairment | Not formally studied | Use with caution; extensive hepatic metabolism means exposure may be higher No specific dose guidance available from FDA PI | ||
Clinical Pearl — Delayed Onset of Action
Dutasteride has a markedly long time to steady state. Serum concentrations reach approximately 65% of steady state after one month and 90% after three months. Patients should be counselled that noticeable improvements in urinary symptoms may take three to six months, and maximum reduction in prostate volume occurs at six to twelve months. Premature discontinuation for perceived lack of benefit is a common pitfall.
Pharmacology
Mechanism of Action
Dutasteride is a competitive, specific inhibitor of both type 1 and type 2 isoforms of the enzyme 5-alpha-reductase. This enzyme converts testosterone to dihydrotestosterone (DHT), the principal androgen driving prostatic growth. Unlike finasteride, which inhibits only the type 2 isoform, dutasteride blocks both isoforms and forms a highly stable enzyme complex with extremely slow dissociation. At steady state, dutasteride suppresses serum DHT concentrations by approximately 90–95%, compared with approximately 70% suppression seen with finasteride. Importantly, dutasteride does not bind to the human androgen receptor. The resulting reduction in intraprostatic DHT leads to progressive shrinkage of the prostate gland, improved urinary flow, and reduced risk of acute urinary retention and surgical intervention.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability ~60% (range 40–94%); Tmax 2–3 h; food reduces Cmax by 10–15% | Food effect is not clinically significant; can be taken with or without meals |
| Distribution | Vd 300–500 L; protein binding 99% (albumin), 96.6% (AAG); 11.5% partitions into semen | Large Vd reflects extensive tissue distribution; semen levels are clinically relevant for teratogenicity counselling |
| Metabolism | Hepatic via CYP3A4 and CYP3A5; major metabolites include 4′-hydroxy, 6-hydroxy, and 1,2-dihydrodutasteride | CYP3A4 inhibitors may increase dutasteride exposure; does not inhibit major CYP isoenzymes at clinical concentrations |
| Elimination | Terminal t½ ~5 weeks at steady state; ~5% excreted in faeces as unchanged drug, ~40% as metabolites; <1% in urine | Extremely long half-life means detectable serum levels persist 4–6 months after discontinuation; blood donation must be deferred ≥6 months |
Side Effects
≥10%
Very Common (Combination Therapy)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Ejaculation disorders (combination therapy) | 11% (cumulative, CombAT) | Significantly higher than either dutasteride monotherapy (2%) or tamsulosin monotherapy (4%); includes retrograde ejaculation, reduced semen volume, and anorgasmia. Most common during the first 6 months (7.8%). No monotherapy adverse effect reaches the ≥10% threshold. |
1–10%
Common
| Adverse Effect | Incidence (Monotherapy) | Incidence (Combination) | Clinical Note |
|---|---|---|---|
| Impotence (erectile dysfunction) | 4.7% (months 0–6) | 5.4% (year 1) | Highest incidence in first 6 months; tends to decline with continued treatment; may persist after discontinuation in rare cases |
| Decreased libido | 3.0% (months 0–6) | 4.5% (year 1) | More common in combination therapy; usually resolves over time; placebo rate was 1.4% (monotherapy) |
| Ejaculation disorders | 1.4% (months 0–6) | 7.8% (year 1) | Includes retrograde ejaculation and reduced semen volume; significantly more common with combination therapy (up to 11% cumulative) |
| Breast disorders (gynecomastia, tenderness) | 0.5–1.1% (varies by time period) | 0.9–1.1% (year 1) | Incidence increases slightly with longer treatment duration; includes breast enlargement and tenderness |
| Dizziness | <1% | 1.1% (year 1) | Primarily reported in CombAT (combination therapy); may be attributable to tamsulosin component |
Serious
Serious (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| High-grade prostate cancer (Gleason 8–10) | 1.0% vs 0.5% placebo | Years 3–4 (REDUCE trial) | Ensure appropriate prostate cancer screening before and during treatment; PSA values must be doubled for comparison with untreated men |
| Cardiac failure (composite) | 0.6–0.7% | Over 4-year treatment course | Monitor patients with cardiac comorbidities; no causal relationship established per FDA |
| Angioedema / serious hypersensitivity reactions | Rare (postmarketing) | Any time during therapy | Discontinue immediately; emergency treatment; permanent discontinuation; contraindicated for re-challenge |
| Serious skin reactions (e.g., skin peeling) | Rare (postmarketing) | Variable | Discontinue; dermatology consultation; do not rechallenge |
| Male breast cancer | Very rare (postmarketing) | Long-term use | Evaluate any breast lumps or nipple discharge; relationship to dutasteride not established |
| Depressed mood | Rare (postmarketing) | Variable | Screen for mood changes at follow-up visits; consider discontinuation if significant |
| Testicular pain and swelling | Rare (postmarketing) | Variable | Evaluate to exclude torsion or other acute pathology; consider discontinuation if persistent |
Discontinuation
Discontinuation Rates
Monotherapy (Placebo-Controlled Trials)
4% vs 3% placebo
Top reason: Impotence (1%)
Combination Therapy (CombAT Trial)
6% vs 4% monotherapy
Top reason: Erectile dysfunction (1–1.5%)
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Impotence / erectile dysfunction | 1–1.5% | Most common reason across both monotherapy and combination trials |
| Ejaculation disorders | <1% | Higher in combination therapy arm |
| Breast disorders | <0.5% | Rarely the sole reason for stopping treatment |
Management — Sexual Adverse Effects
Sexual side effects are most pronounced in the first six months and tend to improve with continued therapy. Patients should be informed that these effects may persist after discontinuation in some individuals, though the role of dutasteride in persistence remains unclear (FDA PI). A frank discussion of sexual side effects before initiating treatment can improve adherence and reduce nocebo-related complaints.
Drug Interactions
Dutasteride is metabolised primarily by CYP3A4 and CYP3A5. It does not inhibit major CYP isoenzymes at clinically relevant concentrations, which limits its potential as a perpetrator of interactions. The principal concern is with potent CYP3A4 inhibitors that may increase dutasteride exposure. Dutasteride does not alter the pharmacokinetics of warfarin, digoxin, tamsulosin, or terazosin.
Major
Ritonavir & other potent CYP3A4 inhibitors
MechanismPotent CYP3A4 inhibition decreases dutasteride clearance
EffectPotentially significant increase in dutasteride serum levels (magnitude not clinically quantified)
ManagementUse with caution; no formal interaction study performed; monitor for increased side effects
FDA PI
Major
Ketoconazole (systemic)
MechanismPotent CYP3A4 inhibition
EffectExpected increase in dutasteride exposure based on in vitro data
ManagementAvoid concomitant chronic use if possible; consider alternative antifungal
FDA PI
Moderate
Verapamil
MechanismCYP3A4 inhibition reduces dutasteride clearance by 37%
EffectIncreased dutasteride exposure; not considered clinically significant per FDA PI
ManagementNo dose adjustment recommended; monitor if additional CYP3A4 inhibitors co-prescribed
FDA PI
Moderate
Diltiazem
MechanismCYP3A4 inhibition reduces dutasteride clearance by 44%
EffectIncreased dutasteride exposure; not considered clinically significant per FDA PI
ManagementNo dose adjustment recommended; amlodipine (non-CYP3A4 inhibitor) is a safe calcium channel blocker alternative
FDA PI
Moderate
CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampicin)
MechanismInduction of CYP3A4 increases dutasteride metabolism
EffectPotentially reduced dutasteride efficacy due to lower serum levels
ManagementMonitor BPH symptoms; consider whether therapeutic response is adequate
Lexicomp
Minor
Warfarin
MechanismNo pharmacokinetic interaction demonstrated
EffectNo change in S- or R-warfarin levels or prothrombin time
ManagementNo adjustment needed; safe to co-prescribe
FDA PI
Minor
Digoxin
MechanismNo pharmacokinetic interaction demonstrated
EffectNo change in digoxin steady-state levels
ManagementNo adjustment needed
FDA PI
Minor
Cholestyramine
MechanismBile acid sequestrant; potential for GI binding
EffectNo effect on dutasteride bioavailability when given 1 hour apart
ManagementNo special precautions required
FDA PIMonitoring
-
PSA
Baseline, then at 3–6 months to establish new baseline
Routine Dutasteride reduces PSA by approximately 50% within 3–6 months. A new PSA baseline must be established after at least 3 months on treatment. Any confirmed increase from the nadir while on therapy should prompt evaluation for prostate cancer, even if the absolute value appears normal for untreated men. To compare with population reference ranges, multiply the measured PSA by 2. -
Digital Rectal Exam
Baseline, then periodically
Routine Prostate cancer should be ruled out before initiation. BPH and prostate cancer can coexist. DRE remains important for screening even though dutasteride reduces prostate volume. -
BPH Symptoms (IPSS/AUA-SI)
Baseline, then every 3–6 months
Routine Quantitative symptom scoring helps track response and identify non-responders. Improvement typically begins at 3 months and plateaus by 6–12 months. -
Sexual Function
At each follow-up visit
Routine Screen for erectile dysfunction, decreased libido, and ejaculation disorders. Address early to prevent unnecessary discontinuation. -
Breast Examination
If symptoms arise
Trigger-based Evaluate any breast lumps, pain, or nipple discharge. Male breast cancer has been reported rarely in postmarketing surveillance. Relationship to dutasteride is not established. -
Hepatic Function
Baseline if clinical concern
Trigger-based Not formally required per labelling, but dutasteride is extensively hepatically metabolised. Consider baseline liver function in patients with known or suspected hepatic disease. -
Mood / Mental Health
At each follow-up visit
Trigger-based Depressed mood has been reported postmarketing. Screen for mood changes, particularly during the first year of treatment.
Contraindications & Cautions
Absolute Contraindications
- Pregnancy and women who may become pregnant: Dutasteride inhibits conversion of testosterone to DHT, which is essential for normal development of male fetal external genitalia. The drug is absorbed through the skin — capsules must not be handled by pregnant or potentially pregnant women (FDA PI).
- Known hypersensitivity: Prior clinically significant hypersensitivity to dutasteride (e.g., angioedema, serious skin reactions) or any other 5-alpha-reductase inhibitor (FDA PI).
- Paediatric patients: Not indicated and not studied in patients under 18 years of age.
Relative Contraindications (Specialist Input Recommended)
- Significant hepatic impairment: Dutasteride is extensively metabolised hepatically. Formal pharmacokinetic studies in hepatic impairment have not been performed. Patients with significant liver disease may have higher drug exposure and should be managed in consultation with a hepatologist or pharmacist with specialist knowledge.
- Active fertility goals: Dutasteride reduces total sperm count (mean 23% reduction at 52 weeks), semen volume (26%), and sperm motility (18%). Two subjects in the pivotal study experienced >90% sperm count decline. Fertility implications should be discussed with a reproductive specialist before initiating therapy in men planning conception.
Use with Caution
- Patients undergoing PSA screening: Dutasteride halves PSA values, potentially masking prostate cancer. A new baseline must be established at 3–6 months and values doubled for comparison with untreated reference ranges.
- Concomitant potent CYP3A4 inhibitors: Long-term use of drugs such as ritonavir, ketoconazole, or itraconazole may increase dutasteride exposure.
- Patients with cardiovascular comorbidities: A numerical excess of composite cardiac failure was observed in the CombAT trial (0.7% combination vs. 0.1% dutasteride monotherapy) and the REDUCE trial (0.6% dutasteride vs. 0.4% placebo). No causal relationship has been established.
- Blood donation: Patients must defer blood donation for at least 6 months after their last dose to prevent inadvertent transfusion to a pregnant recipient.
FDA Class-Wide Regulatory Warning
Increased Risk of High-Grade Prostate Cancer (5-Alpha-Reductase Inhibitors)
In the 4-year REDUCE trial, men taking dutasteride had a higher incidence of Gleason score 8–10 prostate cancer compared with placebo (1.0% vs. 0.5%). Similar findings were reported with finasteride in the 7-year PCPT (1.8% vs. 1.1%). Whether this reflects a true biological effect or detection bias related to reduced prostate volume remains debated. The FDA has determined that 5-alpha-reductase inhibitors are not approved for prostate cancer prevention (FDA PI, 2011 safety labelling update).
Patient Counselling
Purpose of Therapy
Dutasteride works by blocking the hormone that causes the prostate gland to grow. Over time — typically three to six months — the prostate shrinks, urinary symptoms improve, and the risk of needing surgery or developing a sudden inability to urinate is reduced. It is a long-term treatment; stopping early may allow symptoms to return.
How to Take
Swallow the capsule whole once daily, at any time of day, with or without food. Do not chew, crush, or open the capsule as the contents may irritate the mouth and throat. Missed doses can be taken later the same day but should not be doubled up the following day.
Sexual Side Effects
Tell patient
Some men experience reduced sex drive, difficulty getting or maintaining an erection, or changes in ejaculation. These effects are most common in the first few months and often improve with continued use. In rare cases, they may persist after stopping the medication.
Call prescriber
If sexual side effects are bothersome and do not improve after 3–6 months, or if they cause significant relationship distress.
PSA Screening & Prostate Cancer
Tell patient
This medication halves the PSA blood test value. Inform all healthcare providers and screening programmes about dutasteride use. Any increase in PSA while on treatment should be investigated, even if the number looks normal.
Call prescriber
If notified of any rising PSA value during routine screening, or if new urinary symptoms develop that differ from the original pattern.
Handling Precautions & Women’s Safety
Tell patient
Women who are pregnant or could become pregnant must not handle dutasteride capsules, as the drug can be absorbed through the skin and may harm a developing male fetus. If accidental skin contact occurs, wash the area immediately with soap and water.
Call prescriber
If a pregnant woman is inadvertently exposed to the capsule contents.
Blood Donation
Tell patient
Do not donate blood while taking dutasteride or for at least 6 months after stopping. This prevents a pregnant woman from receiving the drug through a transfusion. The drug remains in the body for several months after the last dose.
Call prescriber
Not applicable; this is a standing instruction.
Breast Changes
Tell patient
A small number of men develop breast tenderness or enlargement while taking dutasteride. This is usually mild and manageable.
Call prescriber
Promptly report any breast lumps, persistent pain, or nipple discharge for evaluation.
Mood Changes
Tell patient
Some patients have reported depressed mood while taking dutasteride. Be aware of any changes in emotional well-being.
Call prescriber
If persistent low mood, loss of interest in activities, or any thoughts of self-harm develop.
Sources
Regulatory (PI / SmPC)
- AVODART (dutasteride) soft gelatin capsules — Full Prescribing Information. GlaxoSmithKline; Revised 01/2020. FDA Label Primary source for all dosing, adverse reaction rates, pharmacokinetic parameters, and contraindications cited in this monograph.
- JALYN (dutasteride and tamsulosin hydrochloride) capsules — Full Prescribing Information. GlaxoSmithKline; Revised 2017. FDA Label Source for fixed-dose combination therapy dosing and CombAT-specific adverse event data.
- FDA Drug Safety Communication: 5-alpha reductase inhibitors may increase the risk of a more serious form of prostate cancer. U.S. FDA; June 2011. FDA.gov Regulatory basis for the class-wide warning on high-grade prostate cancer risk with 5-alpha-reductase inhibitors.
Key Clinical Trials
- Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med. 2010;362(13):1192-1202. doi:10.1056/NEJMoa0908127 The REDUCE trial: 4-year RCT of 8,231 men demonstrating 22.8% relative reduction in prostate cancer risk but increased Gleason 8–10 tumours in years 3–4.
- Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123-131. doi:10.1016/j.eururo.2009.09.035 CombAT trial: demonstrated superiority of combination therapy over monotherapy for BPH symptom improvement and risk reduction at 4 years.
- 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. doi:10.1016/S0090-4295(02)01905-2 Early pivotal trial establishing the dose-response relationship and safety profile of dutasteride in BPH.
- Gubelin Harcha W, Barboza Martínez J, Tsai TF, et al. A randomized, active- and placebo-controlled study of the efficacy and safety of different doses of dutasteride versus placebo and finasteride in the treatment of male subjects with androgenetic alopecia. J Am Acad Dermatol. 2014;70(3):489-498.e3. doi:10.1016/j.jaad.2013.10.049 Phase III dose-ranging trial showing dutasteride 0.5 mg daily was significantly superior to finasteride 1 mg for hair count and width at 24 weeks.
Guidelines
- McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793-1803. doi:10.1016/j.juro.2011.01.074 AUA guidelines recommending 5-alpha-reductase inhibitors for men with demonstrable prostate enlargement and moderate-to-severe LUTS.
- Gravas S, Cornu JN, Gacci M, et al. EAU Guidelines on Management of Non-neurogenic Male Lower Urinary Tract Symptoms (LUTS), incl. Benign Prostatic Obstruction (BPO). European Association of Urology; 2023. EAU Guidelines Current European guideline positioning dutasteride as first-line for men with moderate-to-severe LUTS and prostate volume >40 mL.
Mechanistic / Basic Science
- Clark RV, Hermann DJ, Cunningham GR, et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5-alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004;89(5):2179-2184. doi:10.1210/jc.2003-030330 Key study quantifying the degree of serum and intraprostatic DHT suppression achieved by dual 5-alpha-reductase inhibition.
Pharmacokinetics / Special Populations
- Keam SJ, Scott LJ. Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-485. doi:10.2165/00003495-200868040-00008 Comprehensive pharmacology review covering PK parameters across age groups, protein binding, and metabolic pathway characterisation.
- Debruyne F, Barkin J, van Erps P, et al. Efficacy and safety of long-term treatment with the dual 5-alpha-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia. Eur Urol. 2004;46(4):488-494. doi:10.1016/j.eururo.2004.05.008 Long-term (4-year) safety and efficacy data from the open-label extension of the pivotal BPH trials.