What are the considerations for using a combination of dutasteride (5-alpha-reductase inhibitor) and tadalafil (phosphodiesterase inhibitor) in an older male patient with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED)?

Dutasteride Plus Tadalafil Combination for BPH and Erectile Dysfunction

For older male patients with BPH and erectile dysfunction, initiate dutasteride 0.5 mg once daily combined with tadalafil 5 mg once daily, as this regimen provides dual benefits for both urinary symptoms and sexual function while avoiding the contraindicated combination of tadalafil with alpha-blockers. 1, 2

Why This Specific Combination

Dutasteride Over Finasteride

• Dutasteride achieves 95% DHT suppression compared to finasteride's 70% reduction, providing more complete 5-alpha-reductase inhibition through dual type I and type II isoenzyme blockade 2
• The AUA confirms dutasteride and finasteride have equivalent clinical efficacy and safety profiles, making dutasteride's superior pharmacologic profile the deciding factor 2
• Both agents produce 15-25% prostate volume reduction after 6 months and 3-4 point IPSS improvements maintained for 6-10 years 2

Tadalafil's Dual Role

• Tadalafil 5 mg is the only PDE5 inhibitor licensed specifically for male LUTS treatment 1
• Provides modest but meaningful IPSS reduction of -1.74 points versus placebo 1
• Simultaneously improves erectile function in men with or without baseline ED 3, 4
• The AUA explicitly states that tadalafil should be discussed as a treatment option for LUTS/BPH irrespective of comorbid ED 1

Critical Contraindication to Avoid

Do not combine tadalafil with alpha-blockers—the AUA states this offers no advantages in symptom improvement over either agent alone 1, 2. This is why dutasteride (not an alpha-blocker) is the appropriate 5-ARI partner for tadalafil.

Patient Selection Criteria

This combination is appropriate only when:

• Prostate volume >30cc on imaging, PSA >1.5 ng/mL, or palpable enlargement on DRE 1, 2
• Using 5-ARIs in patients without prostatic enlargement is ineffective and exposes them to unnecessary side effects 2

Treatment Protocol and Timeline

Initiation

• Start both medications simultaneously: dutasteride 0.5 mg daily + tadalafil 5 mg daily 2
• Counsel that 5-ARI effects require 3-6 months to become apparent, with maximum benefit at 6-12 months 2
• Tadalafil provides more immediate symptom relief while awaiting dutasteride's full effect 4

Evidence for Combined Efficacy

• A randomized controlled trial of 695 men demonstrated that tadalafil/finasteride coadministration produced IPSS improvements of -4.0 at 4 weeks, -5.2 at 12 weeks, and -5.5 at 26 weeks, compared to -2.3, -3.8, and -4.5 with placebo/finasteride (p ≤ 0.022 at all timepoints) 4
• The same study showed IIEF-EF improvements of 3.7 at 4 weeks and 4.7 at 12 and 26 weeks with tadalafil/finasteride versus -1.1,0.6, and 0.0 with placebo/finasteride (p <0.001 at all visits) 4
• Significantly larger percentages of sexually active men with baseline ED achieved clinically meaningful IIEF-EF improvements (≥4 points) at 4,12, and 26 weeks with tadalafil/5-ARI versus placebo/5-ARI (p <0.001) 3

Monitoring Requirements

PSA Management

• PSA decreases by approximately 50% after 1 year of dutasteride therapy 2
• Double the measured PSA value after 1 year for accurate prostate cancer screening interpretation 1, 2
• Failure to adjust PSA values can lead to delayed cancer diagnosis and worse cancer-specific outcomes 1

Clinical Follow-Up

• Reassess IPSS and erectile function at 4-6 weeks and 3 months 2
• Monitor blood pressure if patient has hypertension, as tadalafil requires caution in poorly controlled hypertension 1, 2

Safety Considerations and Contraindications

Tadalafil-Specific Contraindications

• Absolute contraindications: concurrent nitrate use, guanylate cyclase stimulators, severe uncontrolled hypertension, recent stroke (<6 months), significant hepatic/renal insufficiency, or history of anterior ischemic optic neuropathy with prior PDE5I use 1, 2
• Pacemakers are NOT a contraindication to tadalafil 2
• Common adverse effects include flushing, headache, dyspepsia, back pain, and nasal congestion 1

Dutasteride-Specific Adverse Effects

• Decreased libido: 6.4% in first year (decreases to 2.6% in years 2-4) 2
• Ejaculatory dysfunction: 3.7% in first year (decreases to 1.5% in years 2-4) 2
• Sexual adverse events are typically mild and decrease after the first year 3, 4

Protective Effect on Sexual Function

• The combination of tadalafil with a 5-ARI may actually mitigate the sexual dysfunction typically associated with 5-ARI monotherapy 3, 5
• In the tadalafil/finasteride study, only 5 patients reported sexual adverse events versus 7 in the placebo/finasteride group 3
• This represents a major advantage over traditional 5-ARI/alpha-blocker combinations 5

Common Pitfalls to Avoid

1. Do not prescribe this combination without documenting prostatic enlargement (>30cc)—5-ARIs are ineffective in smaller prostates 1, 2

2. Do not combine tadalafil with alpha-blockers—this provides no additional benefit per AUA guidelines 1, 2

3. Do not fail to double PSA values after 1 year of dutasteride therapy when screening for prostate cancer 1, 2

4. Do not prescribe tadalafil to patients on nitrates or with recent stroke (<6 months)—these are absolute contraindications 1, 2

5. Do not expect immediate results from dutasteride—counsel patients that full benefit requires 6-12 months 2

6. Do not discontinue therapy prematurely—allow at least 6 months to assess dutasteride effectiveness 2

Cardiovascular Considerations

• Dutasteride has no direct cardiovascular effects and does not interfere with antihypertensive medications 2
• Tadalafil can be used cautiously in patients with controlled hypertension but requires blood pressure monitoring 2
• This combination is safer from a cardiovascular standpoint than alpha-blocker combinations, which carry orthostatic hypotension risk 2