What is the recommended starting dose of sildenafil (phosphodiesterase type 5 inhibitor) for a patient with erectile dysfunction (ED)?

Sildenafil Starting Dose for Erectile Dysfunction

The recommended starting dose of sildenafil for erectile dysfunction is 50 mg, taken approximately 1 hour before sexual activity, with subsequent titration to 100 mg if inadequate or reduction to 25 mg based on tolerability. 1

Standard Dosing Protocol

• Start with 50 mg taken approximately 1 hour before sexual activity, not more than once daily. 1, 2
• Sexual stimulation is mandatory for the medication to work—this is a critical point that must be emphasized to patients. 1
• If the 50 mg dose proves inadequate after proper use, titrate up to 100 mg (the maximum dose). 1
• If side effects are problematic at 50 mg, reduce to 25 mg. 1

Special Populations Requiring 25 mg Starting Dose

Lower your starting dose to 25 mg in the following situations:

• Severe hepatic impairment (severe hepatic disease is generally a contraindication). 1
• Renal impairment (creatinine clearance <30 mL/min). 1
• Concurrent CYP3A4 inhibitors including ritonavir, saquinavir, ketoconazole, erythromycin, or cimetidine. 1
• Age ≥65 years may warrant consideration of 25 mg initiation. 2

Critical Safety Screening Before Prescribing

Absolute contraindication: Concurrent nitrate use (organic nitrates, glyceryl trinitrate, isosorbide dinitrate) due to potentially fatal hypotension. 1

High-risk cardiovascular conditions requiring cardiac stabilization before treatment: 1

• Unstable or refractory angina
• Uncontrolled hypertension
• Recent MI or stroke (within 2 weeks)
• Severe heart failure (NYHA class II or higher)

Emergency nitrate protocol: If a patient on sildenafil requires emergency nitrates, wait at least 24 hours after the last sildenafil dose before administering nitrates under close medical supervision. 1, 3

Defining an Adequate Trial Before Declaring Failure

Before concluding that sildenafil is ineffective, ensure the following:

• At least 5 separate attempts at maximum dose (100 mg) have been completed. 1
• Address modifiable factors that account for most "treatment failures": 1
  • Inadequate sexual stimulation (required for efficacy)
  • Improper timing of dose (should be taken ~1 hour before activity)
  • Taking with large meals (delays absorption)
  • Heavy alcohol use (impairs erectile function)
  • Relationship issues with partner

Expected Efficacy

• Success rate: 69% of men achieve successful sexual intercourse attempts vs 35.5% with placebo. 1
• Erection improvement: 73-88% report improved erections vs 26-32% with placebo. 1, 3
• Efficacy is maintained across various etiologies including diabetes, cardiovascular disease, depression, spinal cord injury, and post-prostatectomy, though response rates may be lower in these populations. 1, 4

Dose-Response Relationship

• 50 mg is superior to 25 mg, but the incremental benefit of 100 mg over 50 mg is less pronounced. 1, 3
• Some studies suggest that starting with 100 mg may reduce anxiety about the next intercourse attempt (56% felt no anxiety with 100 mg vs 39% with 50 mg) and improve treatment satisfaction, without increasing adverse events. 5
• However, guideline recommendations consistently support 50 mg as the starting dose with titration as needed. 1

Common Adverse Effects

The most frequent side effects are transient and mild-to-moderate: 1

• Headache
• Flushing
• Dyspepsia
• Nasal congestion
• Abnormal vision

Practical Prescribing Pearls

• Avoid taking with large meals, which delays absorption and reduces efficacy. 1
• Sexual stimulation is non-negotiable for effectiveness—many "failures" result from patients expecting spontaneous erections without stimulation. 1
• Consider checking testosterone levels in patients with suboptimal response, as low testosterone (<300 ng/dL) may benefit from combination therapy with testosterone replacement. 1
• Periodic follow-up should assess efficacy, side effects, cardiovascular health changes, and new medications (particularly CYP3A4 inhibitors). 1, 3

When to Switch Therapies

If sildenafil fails after an adequate trial (at least 5 attempts at 100 mg with proper use), consider: 1

• Switching to a different PDE5 inhibitor (tadalafil or vardenafil)
• Evaluating for hormonal abnormalities
• Considering alternative therapies