What is the recommended dosage and treatment approach for an adult male with erectile dysfunction considering avanafil (phosphodiesterase type 5 inhibitor)?

Avanafil for Erectile Dysfunction

For adult males with erectile dysfunction, start avanafil at 100 mg taken orally approximately 15 minutes before sexual activity, with dose titration to 200 mg or reduction to 50 mg based on efficacy and tolerability. 1

Initial Dosing and Administration

• The FDA-approved starting dose is 100 mg taken as early as 15 minutes before sexual activity 1
• The dose may be increased to 200 mg (taken 15 minutes before activity) or decreased to 50 mg (taken 30 minutes before activity) based on individual response 1
• Maximum dosing frequency is once per day 1
• Avanafil may be taken with or without food 1
• Sexual stimulation is required for the medication to work—this is a critical point for patient education, as incorrect use accounts for many treatment failures 2, 3

Dose Titration Strategy

• Titrate to the lowest dose that provides adequate benefit while minimizing adverse effects 4, 2, 3
• For patients with diabetes or post-prostatectomy ED, consider starting at the higher end of the dosing range (200 mg), as these populations have more severe baseline ED and respond less robustly to all PDE5 inhibitors 2, 3
• An adequate trial requires at least 5 separate attempts at the maximum tolerated dose before declaring treatment failure 2

Efficacy Profile

• Avanafil has similar efficacy to sildenafil, tadalafil, and vardenafil in the general ED population 4, 2, 3
• In clinical trials, avanafil 100 mg demonstrated significantly greater improvements in successful vaginal penetration (SEP2) and successful intercourse (SEP3) compared to placebo 5
• Approximately two-thirds of sexual intercourse attempts made within 15 minutes or beyond 6 hours after dosing were successful with avanafil, compared to one-quarter with placebo 6
• For men with both ED and testosterone deficiency, combining avanafil with testosterone therapy may improve efficacy beyond avanafil alone 2

Safety and Adverse Effects

• Most common adverse events include headache, flushing, nasal congestion, nasopharyngitis, and back pain 2, 6, 7
• Avanafil has the lowest rates of dyspepsia among all PDE5 inhibitors 2, 3
• Like tadalafil, avanafil has lower rates of myalgia compared to other PDE5 inhibitors 2
• In pooled analyses, ≤2% of patients discontinued treatment due to adverse events 6
• During extended treatment (>52 weeks), only 2.8% discontinued due to adverse reactions with no drug-related serious adverse events 6

Critical Contraindications and Drug Interactions

• Avanafil is absolutely contraindicated with any form of nitrates due to potentially fatal hypotension 3, 1
• If nitrate administration becomes medically necessary after avanafil use, wait at least 12 hours after the last dose and administer only under close medical supervision with hemodynamic monitoring 1
• Do not use avanafil with strong CYP3A4 inhibitors (ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) 1
• For moderate CYP3A4 inhibitors (erythromycin, amprenavir, aprepitant, diltiazem, fluconazole, fosamprenavir, verapamil), the maximum dose is 50 mg once every 24 hours 1
• If co-administering with alpha-blockers, patients must be stable on alpha-blocker therapy first, and avanafil should be initiated at 50 mg 1

Cardiovascular Risk Assessment

• Before prescribing avanafil, assess cardiovascular risk by determining if the patient can walk 1 mile in 20 minutes or climb 2 flights of stairs in 20 seconds 2
• Men unable to perform this level of exercise without symptoms should be referred to cardiology before treatment 2
• ED itself is a significant independent risk marker for cardiovascular disease, as strong a predictor as smoking or family history of MI 4

Special Populations

• Use with caution at lower doses initially in patients with mild to moderate hepatic or renal impairment 2
• No dosage adjustments are warranted based on renal function, hepatic function, age, or gender for standard populations 7
• Men with diabetes and post-prostatectomy patients have more severe baseline ED and may respond less robustly—consider higher initial dosing 2, 3

Optimizing Treatment Success

• Verify adequate sexual stimulation is occurring, as this is necessary for efficacy 2, 3
• Before declaring treatment failure, evaluate: hormonal abnormalities, food/drug interactions, timing and frequency of dosing, adequacy of sexual stimulation, heavy alcohol use, and relationship issues 2
• Proper patient education is essential—many apparent failures result from inadequate trials, improper timing, or lack of sexual stimulation 2, 3
• Consider psychological factors (depression, anxiety, relationship conflict) and offer referral to psychotherapy as adjunct to medical treatment 4