Sildenafil for Erectile Dysfunction
Sildenafil is a safe and highly effective first-line oral therapy for erectile dysfunction in adult males, with 69% of men achieving successful sexual intercourse compared to 35.5% with placebo, but it is absolutely contraindicated in patients taking any form of nitrate medication due to the risk of life-threatening hypotension. 1, 2
Patient Selection and Safety Screening
Before prescribing sildenafil, you must verify the following:
- Absolutely exclude nitrate use in any form (oral, sublingual, transdermal, or recreational) as the combination can cause potentially fatal hypotension 1, 3
- Assess cardiovascular fitness by asking if the patient can walk 1 mile in 20 minutes or climb 2 flights of stairs without symptoms; refer to cardiology if unable to perform this level of activity 1
- Most ED patients are low-risk and can safely receive sildenafil, including those with asymptomatic coronary artery disease with <3 risk factors, controlled hypertension, mild stable angina, successful coronary revascularization, uncomplicated past MI, mild valvular disease, and CHF (NYHA class I) 1
High-Risk Patients Who Should Defer Treatment
The following patients should defer sildenafil until their cardiac condition is stabilized 1:
- Unstable or refractory angina
- Recent myocardial infarction or stroke (within 2 weeks)
- Heart failure NYHA Class III-IV
- High-risk arrhythmias
- Hypertrophic obstructive cardiomyopathy
Patients Requiring Cardiovascular Assessment Before Treatment
These patients need cardiology evaluation before prescribing 1:
- 3 or more cardiac risk factors
- Moderate stable angina
- Recent myocardial infarction (within 2-6 weeks)
- Heart failure NYHA Class II
Dosing Strategy
Start with 50 mg taken approximately 1 hour before sexual activity, no more than once daily. 4
- Dose adjustment: Titrate to 100 mg if 50 mg is well-tolerated but suboptimal, or reduce to 25 mg in elderly patients, those with hepatic/renal impairment, or those taking CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, erythromycin, cimetidine) 1, 4
- Dose-response relationship: Improvement in erectile function is dose-related, with 50 mg more effective than 25 mg, though 100 mg shows minimal additional benefit over 50 mg 1
Defining Treatment Success and Failure
Before declaring treatment failure, patients must complete at least 5 separate attempts at maximum tolerated dose. 1
Common Reasons for Apparent Treatment Failure
Evaluate and address these modifiable factors before escalating dose or switching therapy 1:
- Lack of sexual stimulation (sildenafil requires sexual arousal to work)
- Improper timing (taking too close to or too far from sexual activity)
- Large meals (taking with substantial food intake reduces efficacy)
- Heavy alcohol use (impairs erectile function independent of medication)
- Hormonal abnormalities (men with testosterone deficiency respond less robustly)
- Relationship issues with partner
Special Populations
Testosterone Deficiency
- Check testosterone levels if response to sildenafil is suboptimal 1
- Combining sildenafil with testosterone therapy is more effective than sildenafil alone in men with confirmed hypogonadism (total testosterone <300 ng/dL) 1, 2
- Testosterone therapy alone is not effective monotherapy for ED 5
Diabetes and Post-Prostatectomy
- Sildenafil remains effective in these populations, though baseline ED severity is greater and response may be less robust 1, 2
- These patients particularly benefit from adequate trials at maximum dose before declaring failure 1
Severe Hepatic Impairment
- PDE5 inhibitors are generally not recommended in patients with severe hepatic impairment 1
Adverse Effects and Safety Monitoring
Common Adverse Effects (Transient and Mild-to-Moderate)
- Headache, flushing, dyspepsia, nasal congestion, and abnormal vision (color-tinge, increased light sensitivity, or blurred vision) 3, 4
- Higher doses increase risk of adverse effects, particularly flushing, diarrhea, myalgia, and visual disturbances 3
Serious Adverse Events (Rare, <2% of patients)
- Visual loss: Non-arteritic anterior ischemic optic neuropathy (NAION) has been reported; advise patients to seek immediate medical attention for sudden vision loss in one or both eyes 3
- Hearing loss: Sudden decrease or loss of hearing, sometimes with tinnitus and dizziness; advise prompt medical attention 3
- Priapism: Erections lasting >4 hours require immediate medical assistance; >6 hours can cause permanent penile tissue damage 3
- Use with caution in patients with anatomical penile deformation or conditions predisposing to priapism (sickle cell anemia, multiple myeloma, leukemia) 3
Cardiovascular Events
- Serious cardiovascular events (MI, sudden cardiac death, ventricular arrhythmia, cerebrovascular hemorrhage) have been reported in temporal association with sildenafil use, but most patients had preexisting cardiovascular risk factors 3
- No significant difference in cardiovascular event rates between sildenafil and placebo in clinical trials 6, 7
Ongoing Management and Follow-Up
Periodic follow-up (ideally between 4 weeks and 6 months) should assess: 1
- Efficacy and treatment effectiveness
- Side effects and tolerability
- Verification that cardiovascular health hasn't changed
- Review of new medications (especially nitrates)
- Changes in overall health status
Alcohol Interaction
- Sildenafil can be taken with alcohol, but heavy alcohol use should be avoided as it impairs erectile function and increases risk of adverse effects 8
- Heavy alcohol use is a modifiable factor that should be addressed before declaring treatment failure 8
Critical Safety Warnings
- Never combine with other PDE5 inhibitors (including sildenafil marketed for pulmonary hypertension) 3
- Emergency nitrate protocol: If a patient on sildenafil requires emergency nitrate administration, wait 24 hours after sildenafil before giving nitrates, under close medical supervision 8
- Bleeding disorders and peptic ulceration: Safety is unknown in these patients 3