What is the recommended dosing for sildenafil (phosphodiesterase type 5 inhibitor) in patients with erectile dysfunction (ED)?

Sildenafil Dosing for Erectile Dysfunction

Start sildenafil at 50 mg taken approximately 1 hour before sexual activity (not more than once daily), then titrate to 100 mg if inadequate response or reduce to 25 mg if side effects occur. 1

Standard Dosing Protocol

• Starting dose: 50 mg taken approximately 1 hour before anticipated sexual activity, with a maximum frequency of once daily 1, 2
• Titration strategy: Increase to 100 mg (maximum dose) if 50 mg provides inadequate efficacy, or decrease to 25 mg if tolerability issues arise 1, 2
• Sexual stimulation is mandatory for sildenafil to be effective—the medication enhances but does not initiate erections 1

Dose-Response Relationship

• Sildenafil demonstrates dose-dependent improvement in erectile function, with 50 mg superior to 25 mg 1
• Success rates with sildenafil are 69% for successful intercourse attempts versus 35.5% with placebo 1
• Starting at 100 mg reduces anxiety about the next intercourse attempt (56% felt no anxiety with 100 mg vs 39% with 50 mg) and improves treatment satisfaction, with no increase in adverse events 3

Defining an Adequate Trial Before Declaring Failure

• Require at least 5 separate attempts at maximum dose (100 mg) before concluding treatment failure 1
• Many apparent failures result from modifiable factors: inadequate sexual stimulation, improper timing (not waiting 1 hour), taking with large meals (delays absorption), heavy alcohol use, or relationship issues 1
• Consider switching to a different PDE5 inhibitor (tadalafil or vardenafil) if sildenafil fails after an adequate trial 4

Special Population Dosing Adjustments

Start at 25 mg in the following situations: 1

• Severe hepatic impairment (though generally not recommended) 5
• Significant renal impairment
• Concurrent use of CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, erythromycin, cimetidine) 2
• Elderly patients may benefit from lower starting doses

Critical Safety Contraindications

• Absolute contraindication: Concurrent nitrate use (organic nitrates, nitroglycerin, isosorbide) due to potentially fatal hypotension 1
• Emergency protocol: Wait at least 24 hours after sildenafil before administering nitrates under close medical supervision 4, 1
• High-risk cardiovascular conditions requiring cardiac stabilization first: unstable angina, uncontrolled hypertension, recent MI or stroke (within 2 weeks), severe heart failure (NYHA class II or higher) 1

Efficacy Across Different Etiologies

• Sildenafil maintains efficacy across various causes: diabetes (56% improved erections vs 10% placebo), cardiovascular disease, depression, spinal cord injury (75% improved vs 7% placebo), and post-prostatectomy 6, 7, 8
• Men with diabetes and post-prostatectomy patients have more severe baseline ED and may respond less robustly, but still achieve significant benefit compared to placebo 1, 7

Combination Therapy for Enhanced Response

• If testosterone is <300 ng/dL: Add testosterone replacement therapy to sildenafil, as combination therapy is more effective than either alone 9, 4
• Testosterone therapy alone is not effective monotherapy for ED 5
• Check morning total testosterone, free testosterone, and SHBG in all men with inadequate response to PDE5 inhibitors 4

Common Adverse Effects

• Most frequent side effects (transient and mild-to-moderate): headache (11%), flushing, dyspepsia (9%), nasal congestion (6%), and abnormal vision 1, 6
• Cardiovascular adverse events are comparable to placebo (3% sildenafil vs 5% placebo) 6

Ongoing Management and Follow-Up

• Periodic assessment should verify: cardiovascular health stability, new medications (especially nitrates), treatment effectiveness, and side effects 1
• Before switching therapies, systematically evaluate: hormonal abnormalities, proper timing and frequency of dosing, adequacy of sexual stimulation, heavy alcohol use, and relationship issues 9, 1