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

The recommended starting dose of sildenafil for erectile dysfunction is 50 mg, taken approximately 1 hour before sexual activity, not more than once daily. 1

• The dose should be titrated based on efficacy and tolerability: up to 100 mg or down to 25 mg 1
• For patients with hepatic or renal impairment, start with 25 mg 1
• Taking sildenafil on an empty stomach maximizes efficacy, as food reduces absorption 1

Dose Optimization Strategy

Before declaring treatment failure, patients must complete at least 5 separate attempts at the maximum dose (100 mg). 1, 2

• Start with 50 mg for most patients 1
• If inadequate response after 5 attempts, titrate to 100 mg 1
• Sildenafil demonstrates dose-dependent efficacy (50 mg vs 25 mg), though the incremental benefit from 50 mg to 100 mg is less pronounced 2
• Many apparent failures result from inadequate trials, improper timing, lack of sexual stimulation, or taking with food 1

Critical Patient Education

Sexual stimulation is absolutely necessary for sildenafil to work—it has no effect in the absence of arousal. 1, 3, 4

• Sildenafil enhances the natural erectile response to sexual stimulation by inhibiting PDE5, which allows nitric oxide-mediated smooth muscle relaxation 3, 4
• Patients should be counseled on proper timing (1 hour before activity), avoiding large meals, and ensuring adequate sexual stimulation 1
• The elimination half-life is 3-5 hours 3

Absolute Contraindications

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

• Patients must be explicitly asked about all forms of nitrate use, including sublingual nitroglycerin, long-acting nitrates, and recreational "poppers" 1
• If emergency nitrate administration is required, wait 24 hours after sildenafil use, under close medical supervision 5

Cardiovascular Risk Stratification

Most ED patients can safely receive sildenafil, including those with asymptomatic coronary artery disease, controlled hypertension, mild stable angina, successful coronary revascularization, uncomplicated past MI, mild valvular disease, and CHF (NYHA class I). 1, 2

• Patients whose cardiovascular risk is indeterminate or who cannot perform moderate physical activity should be referred to cardiology before prescribing 1
• ED itself is a significant independent risk marker for cardiovascular disease, comparable to smoking or family history of MI 5

Special Populations

Patients with diabetes or post-prostatectomy have more severe ED at baseline and respond less robustly to sildenafil, often requiring the maximum 100 mg dose. 1, 2

• Men with testosterone deficiency (<300 ng/dL) respond less robustly to sildenafil alone 2
• Combining sildenafil with testosterone therapy is more effective than sildenafil alone in men with confirmed hypogonadism 2
• However, testosterone therapy alone is not effective monotherapy for ED 5

Efficacy Data

Clinical trials demonstrate 69% successful intercourse attempts with sildenafil versus 35.5% with placebo. 1

• Treatment response (defined as clinically meaningful improvement) occurs in 77% of men without comorbidities, 71% with cardiovascular disease/hypertension, 63% with diabetes, and 78% with depression 6
• Efficacy is maintained in long-term (1-year) studies 3

Common Adverse Events

The most frequently reported side effects include headache, flushing, dyspepsia, nasal congestion, and abnormal vision. 1

• These adverse events are typically transient and mild to moderate 3, 4
• Serious adverse events occur in <2% of patients, with no significant difference from placebo 2
• Average rates of adverse events follow a dose-response pattern 5

Ongoing Management and Follow-Up

Periodic follow-up should assess efficacy, side effects, and any significant changes in health status or medications. 5, 2

• Verify that cardiovascular health hasn't changed 2
• Review new medications, particularly nitrates or CYP3A4 inhibitors (ritonavir, ketoconazole, erythromycin) which require dose reduction to 25 mg 3
• Reassess treatment effectiveness and tolerability 5

Addressing Treatment Failures

Before switching to alternative therapies, evaluate whether the sildenafil trial was adequate by addressing modifiable factors. 5, 1

• Check for hormonal abnormalities (testosterone deficiency) 5
• Assess for food or drug interactions 5
• Verify proper timing and frequency of dosing 5
• Ensure adequate sexual stimulation 5
• Evaluate heavy alcohol use and relationship issues with partner 5
• After re-education and dose optimization, some initial non-responders become successful 5

Alternative PDE5 Inhibitors

If sildenafil fails after an adequate trial at maximum dose, consider switching to a different PDE5 inhibitor (tadalafil, vardenafil, or avanafil), as individual response may vary. 5