What is the recommended starting dose of sildenafil (Viagra) for an adult man with erectile dysfunction, and how should it be adjusted in hepatic or renal impairment?

Sildenafil (Viagra) Dosing for Erectile Dysfunction

Start with sildenafil 50 mg taken approximately 1 hour before sexual activity, then titrate to 100 mg if inadequate response or reduce to 25 mg if side effects occur or in special populations (hepatic/renal impairment, elderly >65 years, or concurrent CYP3A4 inhibitor use). 1, 2, 3

Standard Dosing Protocol

• Initial dose: 50 mg taken 1 hour before anticipated sexual activity, maximum once daily 1, 2, 3
• Titration upward: Increase to 100 mg (maximum dose) if 50 mg provides insufficient erectile improvement after completing an adequate trial of at least 5 separate attempts with proper technique 1, 2
• Titration downward: Reduce to 25 mg if side effects are bothersome at 50 mg 1, 3
• Dose-response relationship: Sildenafil demonstrates dose-dependent efficacy, with 50 mg superior to 25 mg, though the incremental benefit of 100 mg over 50 mg is less pronounced 4, 2

Special Population Dosing Adjustments

Hepatic Impairment

• Mild to moderate impairment: No dose adjustment required 5
• Severe hepatic impairment: Start with 25 mg; use is generally not recommended per AUA guidelines 6, 1

Renal Impairment

• All degrees of renal impairment (including severe CrCl <30 mL/min): Start with 25 mg for initial caution, though FDA labeling states no adjustment is strictly required 1, 5, 3
• Practical approach: Begin at 25 mg in moderate-to-severe renal disease given potential for delayed metabolism 6

Drug Interactions Requiring Dose Reduction

• CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, erythromycin, cimetidine): Start with 25 mg due to increased sildenafil plasma levels 1, 3

Elderly Patients (≥65 years)

• Starting dose: 25 mg is prudent given greater frequency of decreased hepatic/renal function and concurrent medications, though efficacy is maintained across all age groups including men ≥75 years 5, 3, 7

Critical Safety Requirements Before Prescribing

Absolute Contraindications

• Concurrent nitrate use (organic nitrates, glyceryl trinitrate, isosorbide dinitrate) due to potentially fatal hypotension 1, 8
• Emergency nitrate protocol: Wait at least 24 hours after sildenafil before administering nitrates under close medical supervision 4, 1

High-Risk Cardiovascular Conditions Requiring Stabilization First

• Unstable or refractory angina 1, 8
• Uncontrolled hypertension 1, 8
• Recent myocardial infarction or stroke (within 2 weeks to 6 months depending on severity) 1, 8
• Severe heart failure (NYHA class II or higher) 1
• Severe cardiac failure or impaired cardiac reserve 8

Pre-Treatment Cardiovascular Screening

• Assess functional capacity: Ask if patient can walk 1 mile in 20 minutes or climb 2 flights of stairs without symptoms 4
• Refer to cardiology if unable to perform moderate physical activity or cardiovascular risk is indeterminate 4

Patient Education for Optimal Efficacy

Requirements for Effectiveness

• Sexual stimulation is mandatory—sildenafil enhances but does not replace natural arousal 1, 3
• Timing: Take approximately 1 hour before sexual activity 1, 2, 3
• Avoid large or fatty meals: Food delays absorption and reduces efficacy 4, 1
• Limit alcohol consumption: Heavy alcohol impairs erectile function independent of medication 4

Defining an Adequate Trial Before Declaring Failure

• Minimum requirement: At least 5 separate attempts at the prescribed dose with proper technique (adequate sexual stimulation, correct timing, limited alcohol, no large meals) 4, 1
• Common pitfall: Many "treatment failures" result from incorrect usage rather than true medication inefficacy—up to 30% of apparent non-responders become successful after re-education and proper technique 4, 1

Expected Efficacy and Adverse Effects

Efficacy Outcomes

• Success rate: Approximately 69% report successful sexual intercourse attempts vs. 35.5% with placebo 2, 7
• Improvement in erections: 73-88% vs. 26-32% with placebo 4
• Age-related response: Efficacy maintained across all ages, though percentage reporting improvement decreases slightly with age (<65 years: 80%; 65-74 years: 69%; ≥75 years: 59%) 7

Special Populations with Reduced Response

• Diabetes and post-prostatectomy patients have more severe baseline ED and respond less robustly to PDE5 inhibitors, though sildenafil remains significantly superior to placebo 6, 1, 3
• Spinal cord injury: 76-78% report improved erections and prefer sildenafil to placebo 9

Common Adverse Effects

• Most frequent: Headache, flushing, dyspepsia, nasal congestion, abnormal vision—all transient and mild-to-moderate 1, 3, 7, 8
• Dose-response pattern: Higher doses increase adverse event rates, particularly headache and flushing 6, 7
• Tolerability: Well-maintained in long-term studies; low discontinuation rate (2% vs. 1% placebo) 3, 9

Dose Escalation Strategy

When to Increase from 50 mg to 100 mg

• Erectile function remains suboptimal after completing at least 5 attempts at 50 mg with proper technique 4, 1
• Medication is well-tolerated without bothersome side effects 6, 1
• All modifiable factors addressed: Verify adequate sexual stimulation, proper timing, no large meals, limited alcohol, no relationship issues, and normal testosterone levels 4, 1

Before Escalating Dose, Systematically Evaluate

• Hormonal status: Check testosterone levels—men with testosterone deficiency (<300 ng/dL) respond less robustly; combining sildenafil with testosterone therapy may be more effective than dose escalation alone 4, 1
• Medication interactions: Review for drugs that worsen ED (antihypertensives, antidepressants, opioids) or interact with sildenafil (CYP3A4 inhibitors) 4
• Psychological factors: Screen for depression, anxiety, relationship conflict 4
• Technique errors: Confirm sexual stimulation is occurring, timing is correct, and meals are not interfering 4, 1

When to Switch to Alternative PDE5 Inhibitor

• After failure of sildenafil 100 mg for at least 5 attempts with proper technique and all modifiable factors addressed 4, 1
• Individual response variability: Some men who fail one PDE5 inhibitor achieve success with another (tadalafil or vardenafil), though head-to-head trials show comparable efficacy (~69% response vs. 33% placebo) 4
• Consider tadalafil if patient values sexual spontaneity (36-hour duration) or has coexisting benign prostatic hyperplasia 4

Second-Line Therapies After PDE5 Inhibitor Failure

• Proceed to second-line options only after failure of at least two different PDE5 inhibitors at maximum dose with proper technique 4
• Options include: Intraurethral alprostadil suppositories, intracavernosal injection therapy (most effective non-surgical option), vacuum erection devices, or penile prosthesis implantation 4

Ongoing Management and Follow-Up

• Periodic assessment: Verify cardiovascular health stability, review new medications (especially CYP3A4 inhibitors or nitrates), assess treatment effectiveness, and evaluate side effects 1, 2
• Re-evaluate before switching: Address hormonal abnormalities, drug interactions, timing/frequency of dosing, adequacy of sexual stimulation, heavy alcohol use, and relationship issues 4, 1