What is the complete treatment for erectile dysfunction (ED) grade 2-3?

Complete Treatment for Erectile Dysfunction Grade 2-3

Start with oral PDE5 inhibitors (sildenafil, tadalafil, or vardenafil) as first-line therapy at standard doses, titrating to maximum tolerated dose over at least 5 separate attempts before considering treatment failure. 1

First-Line Pharmacotherapy: PDE5 Inhibitors

Initial Drug Selection and Dosing

• Begin with tadalafil 10 mg as needed, increasing to 20 mg if needed, as it offers a 36-hour window of opportunity and lower rates of flushing compared to other agents 1
• Alternatively, use sildenafil or vardenafil—all three agents have equivalent efficacy (69% success rate vs 35% placebo) in the general ED population 1
• An adequate trial requires at least 5 separate occasions at maximum dose before declaring treatment failure 1, 2

Critical Contraindications

• Never prescribe PDE5 inhibitors to patients taking nitrates—this combination causes potentially fatal hypotension 1
• Avoid vardenafil in patients taking Class 1A antiarrhythmics (quinidine, procainamide) or Class III antiarrhythmics (amiodarone, sotalol), or those with congenital QT prolongation 3
• Defer treatment in high-risk cardiac patients including those with unstable angina, uncontrolled hypertension, recent MI/stroke (within 2 weeks), NYHA class II or greater heart failure, or significant valvular disease 1

Dose Adjustments for Special Populations

• Moderate hepatic impairment (Child-Pugh B): Start vardenafil at 5 mg maximum 10 mg; avoid in severe hepatic impairment 3
• Moderate-to-severe renal impairment: Expect 20-30% higher drug levels; consider dose reduction 3
• Concomitant alpha-blocker use: Start PDE5 inhibitor at lowest dose due to additive hypotensive effects 1, 3
• Potent CYP3A4 inhibitors (azole antifungals, protease inhibitors, macrolides): Reduce PDE5 inhibitor dose 4

Optimizing Failed First-Line Therapy

• Before declaring PDE5 inhibitor failure, re-educate on proper use—this converts up to 30% of non-responders into responders 2
• Address food/drug interactions: high-fat meals delay sildenafil absorption; heavy alcohol impairs erectile function 2
• Measure free testosterone in patients with decreased libido, fatigue, or testicular atrophy, as hypogonadal men often fail PDE5 inhibitors until testosterone is replaced 1, 2
• Try a different PDE5 inhibitor (switch from sildenafil to vardenafil or avanafil), as some patients respond to one agent after failing another 2

Mandatory Lifestyle Modifications

• Counsel all ED patients on risk factor modification regardless of pharmacologic treatment 1
• Recommend smoking cessation, weight loss if overweight, increased physical activity, limiting alcohol consumption, and optimal management of diabetes, hypertension, and dyslipidemia 1

Second-Line Therapies (After Adequate PDE5 Inhibitor Trial)

Intracavernosal Injection Therapy

• Intracavernosal alprostadil injection is the most effective non-surgical treatment with up to 90% success rates 2
• The first dose must be administered under healthcare supervision due to risk of priapism and syncope 2, 5
• Patients should not use more than 3 times per week, with at least 24 hours between injections 5
• If erection persists beyond 6 hours, seek immediate medical attention to prevent permanent penile damage 5

Intraurethral Alprostadil

• Less invasive than injection therapy but lower efficacy than intracavernosal route 2
• First dose must be administered under healthcare supervision due to 3% risk of syncope 2

Vacuum Erection Device (VED)

• Initial efficacy of 90%, though drops to 50-64% at 2 years 2
• Best suited for older patients with infrequent intercourse 2
• Must use vacuum limiters to prevent penile injury from excessive negative pressure 2
• Can be combined with PDE5 inhibitors for improved efficacy 2

Combination Therapy

• Topical alprostadil plus PDE5 inhibitor shows superior efficacy compared to topical alprostadil alone in PDE5 inhibitor non-responders 6
• Combination therapy significantly increased IIEF-5 scores (12.4 to 17.1) and SEP-2/SEP-3 responses without major safety concerns 6

Third-Line Therapy

Penile Prosthesis Implantation

• Definitive surgical option when all medical therapies fail or cause intolerable side effects 1, 2
• Modern devices have low failure and infection rates with high patient and partner satisfaction 2

Common Pitfalls to Avoid

• Do not proceed to invasive therapies without confirming adequate PDE5 inhibitor trial—many "failures" are due to improper use, inadequate dosing, or insufficient attempts 2
• Do not overlook testosterone deficiency, as replacement often restores PDE5 inhibitor responsiveness 2
• Do not prescribe intraurethral or intracavernosal therapy without in-office supervision of first dose 2
• Avoid high-fat meals with sildenafil, which delays absorption 2
• Address relationship factors and partner involvement, as these significantly affect treatment outcomes 2

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