Phosphodiesterase type 5 inhibitors (PDE5)
ATC code: G04BE03 (Sildenafil)
Brand names
Viagra, Revatio
Selective reversible phosphodiesterase type 5 (PDE5) inhibitor. Blocks cGMP breakdown in penile cavernosal smooth muscle during sexual stimulation, producing smooth muscle relaxation and erection. No effect without sexual stimulation — not an «aphrodisiac». Half-life 4 hours, onset 30–60 minutes. Fatty meals delay onset.
First line
First-line for erectile dysfunction per AUA 2018 and EAU 2024. Standard dose 50 mg taken 30–60 minutes before intercourse; titrate up to 100 mg or down to 25 mg. Not more than once daily. Effect lasts up to 4 hours and requires sexual stimulation. In diabetes, post-prostatectomy, or on antihypertensives — usually maximum dose is needed.
First line
Per /ERS 2022, sildenafil is first-line for group 1 pulmonary arterial hypertension in functional class I–III. Dose 20 mg three times daily. Use in specialized centers with confirmed diagnosis and right heart catheterization.
As Revatio 20 mg three times daily.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor. It is prescribed for erectile dysfunction and pulmonary arterial hypertension (AEMPS Ficha Técnica). In anti-aging communities, sildenafil and other PDE5 inhibitors are promoted as rejuvenating, improving cerebral and vascular blood flow, and boosting endurance. In people without erectile dysfunction or pulmonary hypertension, no clinical studies of prophylactic use exist; cerebral blood flow improvement and life extension via PDE5 inhibitors have not been demonstrated. The drug causes headache, facial flushing, nasal congestion, dyspepsia, visual disturbances (bluish tint), and rarely non-arteritic anterior ischemic optic neuropathy (risk of permanent vision loss). It is dangerous combined with nitrates (sharp blood pressure drop, shock risk). If sildenafil is being taken for anti-aging, consider seeking a second opinion.
Not recommended
Sildenafil is marketed for athletic performance and endurance in healthy athletes – particularly during hypoxic or high-altitude training – via systemic vasodilation and improved pulmonary blood flow. WADA has considered PDE5 inhibitors for the Prohibited List since 2009; as of 2026 they are not on the list. ACSM and IOC Medical Commission do not describe clinical indications for sildenafil in healthy athletes – the evidence base for improving general or anaerobic performance in healthy people is absent.
8 pairs found. Sorted from critical to minor.
Mechanism
Sildenafil blocks phosphodiesterase-5, slowing breakdown of cGMP – the intracellular mediator of vascular relaxation. Nitroglycerin raises cGMP production. Co-administration sharply amplifies vasodilation – severe systemic hypotension develops. Fatal cases have been reported.
Symptoms
Sudden drop in blood pressure: dizziness, visual greying, syncope, shock. In ischaemic heart disease, risk of myocardial infarction from coronary perfusion collapse.
Management
The combination is not prescribed. After sildenafil, nitrates are permitted only after 24 hours. After tadalafil (long-acting), only after 48 hours. In acute coronary syndrome after recent sildenafil, replace nitrates with morphine and oxygen; for preload reduction, use furosemide.
Mechanism
Sildenafil is cleared via hepatic CYP3A4. Ritonavir is the strongest CYP3A4 inhibitor available. Sildenafil levels rise 11-fold. The risk of severe hypotension and priapism rises sharply.
Symptoms
Sudden blood pressure drop: dizziness, syncope. Priapism – painful erection lasting more than 4 hours, requiring emergency care. Visual and auditory disturbances are amplified.
Management
For erectile dysfunction on ritonavir, sildenafil is capped at 25 mg no more than once every 48 hours. For pulmonary arterial hypertension (which needs regular high doses), the combination is contraindicated. Alternatives: inhaled iloprost or bosentan with dose adjustment.
Mechanism
Dual mechanism: amiodarone blocks CYP3A4 – a partial sildenafil metabolic route – and both drugs prolong QT. Sildenafil plasma levels rise 2- to 4-fold.
Symptoms
Sudden blood pressure drop: dizziness, syncope. QT prolongation on ECG with torsades de pointes risk. Visual disturbances.
Management
On amiodarone, cap sildenafil at 25 mg (instead of 50–100 mg) and limit to one dose every 48 hours. ECG before start and at 2 weeks; maintain potassium and magnesium.
Mechanism
Clarithromycin blocks CYP3A4 – the main sildenafil metabolic route. Sildenafil plasma levels rise 3- to 5-fold. The hypotensive effect intensifies; priapism and ischaemic optic neuropathy risks rise.
Symptoms
Sudden blood pressure drop: dizziness, syncope. Priapism – painful erection lasting more than 4 hours, requiring emergency care. Worsening of visual disturbances (cyanopsia) and tinnitus.
Management
During clarithromycin therapy, cap sildenafil at 25 mg (instead of the standard 50–100 mg) and limit to one dose every 24 hours. Alternative antibiotics: azithromycin or doxycycline.
Mechanism
Additive hypotensive effect. Sildenafil vasodilates by blocking phosphodiesterase-5; clonidine lowers blood pressure via central α2-agonism. Combined action can cause symptomatic hypotension.
Symptoms
Sudden blood pressure drop: postural dizziness, syncope. Particularly dangerous in older patients and in ischaemic heart disease.
Management
The combination is acceptable in stable hypertension. Cap sildenafil at 25 mg (instead of 50–100 mg). Warn the patient about orthostatic hypotension; take the first dose lying down.
Sources
Mechanism
Ketoconazole strongly blocks CYP3A4 – the main sildenafil metabolic route. Sildenafil plasma levels rise 4- to 8-fold. The hypotensive effect surges; priapism and ischaemic optic neuropathy risks rise.
Symptoms
Sudden blood pressure drop: dizziness, syncope. Priapism – painful erection lasting more than 4 hours. Visual disturbances, tinnitus. Symptoms appear within hours of co-administration.
Management
Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. If ketoconazole is needed, cap sildenafil at 25 mg and one dose per 24 hours.
Mechanism
Additive hypotension via different mechanisms – calcium channel blockade (amlodipine) + PDE5 blockade (sildenafil). Clinically significant in patients with prior hypotension.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.
Management
The combination is acceptable in stable hypertension. Take the first sildenafil dose lying down; do not exceed 25–50 mg. Warn the patient about orthostatic hypotension.
Mechanism
Sildenafil is a vasodilator via PDE5 blockade. Combined with bisoprolol: risk of symptomatic hypotension, especially with the first dose.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk.
Management
The combination is acceptable in stable hypertension with a well-titrated beta-blocker. Take the first sildenafil dose lying down; do not exceed 25–50 mg. Warn the patient about orthostatic hypotension.
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FDA categories were retired in 2015. Not indicated in women for ED. In pregnant patients with PAH, sildenafil is used on strict indication with pulmonologist and cardiologist input.
Not indicated in women for ED. In PAH patients, breastfeeding compatibility is assessed individually.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Sildenafil is evaluated for the following indications with varying evidence strength: Pulmonary arterial hypertension (evidence tier A), Erectile dysfunction (evidence tier A), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Sildenafil (≥ 1 in 100): Headache (10–20 %), Flushing, Dyspepsia, Nasal congestion, Visual disturbances (blue tinge, photophobia, color perception changes), Back pain. See the Safety section for uncommon and serious reactions.
FDA category B. FDA categories were retired in 2015. Not indicated in women for ED. In pregnant patients with PAH, sildenafil is used on strict indication with pulmonologist and cardiologist input.
Not indicated in women for ED. In PAH patients, breastfeeding compatibility is assessed individually.
Sildenafil is contraindicated in: Concurrent nitrates (nitroglycerin, isosorbide dinitrate, amyl nitrite); Concurrent soluble guanylate cyclase stimulators (riociguat); Severe cardiovascular disease in which sexual activity is contraindicated; Severe hepatic impairment; Severe hypotension (SBP below 90). Full list in the Safety section.
PDE5 inhibitors require sexual stimulation — no stimulation, no effect. They are not aphrodisiacs.
in patients without severe CAD and not on nitrates, PDE5 inhibitors are safe. Sexual activity itself does not 'trigger' MI in stable patients.
it is for erectile dysfunction, not duration enhancement or for patients without erectile issues. Use for those purposes risks side effects without benefit.