What is the recommended dosage and usage of Sildenafil (phosphodiesterase type 5 inhibitor) for treating erectile dysfunction (ED)?

Sildenafil for Erectile Dysfunction: Dosing and Management

Starting Dose and Administration

Begin with sildenafil 50 mg taken approximately 1 hour before sexual activity, not more than once daily. 1

• The FDA-approved starting dose is 50 mg for most men with erectile dysfunction 1
• Take on an empty stomach for optimal efficacy, as food (especially large meals) reduces absorption and effectiveness 1
• Sexual stimulation is absolutely necessary for sildenafil to work—this is a critical patient education point that accounts for many apparent treatment failures 1, 2

Dose Titration Strategy

Titrate to 100 mg if inadequate response after at least 5 separate attempts at the starting dose. 1, 3

• Sildenafil demonstrates dose-dependent efficacy: improvement increases from 25 mg to 50 mg to 100 mg 3
• The maximum dose is 100 mg once daily 1
• Reduce to 25 mg in patients with hepatic or renal impairment, elderly patients, or those taking CYP3A4 inhibitors (ritonavir, ketoconazole, erythromycin, cimetidine) 4
• Avoid use entirely in severe hepatic or renal disease 1

Efficacy Data

• Clinical trials show 69% successful intercourse attempts with sildenafil versus 35.5% with placebo 1
• Treatment response rates: 77% in men without comorbidities, 71% with cardiovascular disease/hypertension, 63% with diabetes, and 78% with depression 5
• Men with diabetes and post-prostatectomy patients have more severe ED at baseline and respond less robustly, often requiring the maximum 100 mg dose 1, 3

Absolute Contraindications and Critical Safety

Sildenafil is absolutely contraindicated with any form of nitrate medication due to risk of life-threatening hypotension. 1

• Explicitly ask about all forms of nitrate use before prescribing, including sublingual nitroglycerin, isosorbide mononitrate/dinitrate, and recreational "poppers" (amyl nitrite) 1
• If emergency nitrate administration is required, wait 24 hours after the last sildenafil dose before giving nitrates, under close medical supervision 2, 6

Cardiovascular Risk Stratification

Most ED patients can safely receive sildenafil, including those with asymptomatic coronary artery disease (<3 risk factors), controlled hypertension, mild stable angina, successful coronary revascularization, uncomplicated past MI, mild valvular disease, and CHF (NYHA class I). 1, 3

• Refer patients to cardiology before prescribing if they cannot perform moderate physical activity or have indeterminate cardiovascular risk 1, 6
• Serious adverse events occur in <2% of patients, with no significant difference from placebo 3

Common Adverse Effects

• Headache, flushing, dyspepsia, nasal congestion, and abnormal vision are the most frequent side effects 1, 4
• These are typically transient and mild to moderate in severity 4
• Adverse events follow a dose-response pattern but rarely require discontinuation 2

Optimizing Treatment Response Before Declaring Failure

Before switching therapies, ensure the trial was adequate by addressing modifiable factors. 2, 6

• Verify at least 5 separate attempts at maximum dose (100 mg) 1, 3
• Check for hormonal abnormalities, particularly testosterone deficiency (total testosterone <300 ng/dL)—combining sildenafil with testosterone therapy in hypogonadal men is more effective than sildenafil alone 2, 3
• Assess timing of dosing (1 hour before activity, on empty stomach) 1
• Confirm adequate sexual stimulation is occurring 1, 2
• Evaluate heavy alcohol use, which impairs response 2
• Address relationship issues with partner that may be contributing 2

Special Populations Requiring Dose Adjustment

• Hepatic/renal impairment: Start with 25 mg 1
• Elderly patients: Consider starting with 25 mg 4
• CYP3A4 inhibitor use: Start with 25 mg 4
• Diabetes or post-prostatectomy: Often require 100 mg due to more severe baseline ED 1, 3

Ongoing Monitoring

• Periodically assess efficacy, side effects, and changes in health status including new medications 2, 3
• Verify cardiovascular health has not changed significantly, as this is typically done at prescription renewal 2
• ED serves as a risk marker for cardiovascular disease—communicate this increased risk to the patient and primary care provider 2

Alternative PDE5 Inhibitors

• If sildenafil fails after an adequate trial, consider switching to tadalafil, vardenafil, or avanafil, as some men respond to one PDE5 inhibitor but not another 2
• All FDA-approved PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) have similar efficacy in the general ED population 2