Phosphodiesterase type 5 (PDE-5) inhibitor
Brand names: Levitra, Staxyn
Updated · Methodology
First line
Vardenafil is first-line PDE-5 inhibitor for erectile dysfunction. AEMPS approved 5, 10 and 20 mg doses 25–60 minutes before intercourse. Alternative to sildenafil or tadalafil when one is not tolerated. Not used for pulmonary hypertension (only tadalafil and sildenafil).
Sources
ICD-10: N52.9 · ICD-11: HA01.1
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
Vardenafil is a phosphodiesterase-5 (PDE5) inhibitor. It is prescribed for erectile dysfunction (AEMPS Ficha Técnica). In sports circles, vardenafil is promoted to improve blood flow and physical endurance in healthy athletes. Clinical studies in healthy athletes are insufficient. The drug has specific risks: headache, facial flushing, nasal congestion, dyspepsia, QT prolongation, visual disturbances, and is dangerous combined with nitrates. If vardenafil is used for training, consider seeking a second opinion.
Selective PDE-5 inhibitor with rapid onset (25–60 minutes) and 4–5 hour half-life. Mechanism identical to sildenafil and tadalafil. Metabolised by CYP3A4 and to a lesser extent CYP2C9. Mildly prolongs QT and PR intervals, requiring caution in congenital long QT syndrome.
Not used in women.
Not used in women.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Grapefruit juice weakly inhibits intestinal CYP3A4 and can raise vardenafil levels. Even so, the SmPC says to avoid grapefruit and its juice with vardenafil, a drug that itself slightly lengthens the QT interval. More vardenafil means more headache, flushing, dizziness and a drop in blood pressure.
Source: AEMPS: Ficha técnica de Levatik 10 mg comprimidos bucodispersables EFG (vardenafilo) (2025)
4 pairs found. Sorted from critical to minor.
Mechanism
Vardenafil and isosorbide dinitrate drive the same NO–cGMP signalling pathway from opposite ends. The dinitrate releases nitric oxide in the body and boosts cGMP synthesis in vascular smooth muscle; vardenafil blocks phosphodiesterase-5 and slows the breakdown of that same cGMP. Cyclic GMP accumulates from both directions at once, vascular tone collapses, and additive vasodilation progresses up to refractory hypotension that responds poorly to fluids and vasopressors while both drugs remain active. Unlike sublingual nitroglycerin with its minutes of action, isosorbide dinitrate works for hours and its extended-release forms for most of the day, so the window of danger is stretched out. The Levitra SmPC lists nitrates and other nitric oxide donors as absolute contraindications.
Symptoms
A sharp drop in blood pressure: dizziness, visual greying, reflex tachycardia, cold sweat, syncope. In patients with ischaemic heart disease the collapse of coronary perfusion pressure threatens myocardial infarction. Because the dinitrate is long-acting, hypotension can be prolonged and return in waves as the extended-release form keeps releasing nitrate.
Management
The combination is not prescribed in any form. In a patient on maintenance isosorbide dinitrate, extended-release forms included, vardenafil is contraindicated; the labels give no safe interval for that scenario, and after stopping an extended-release form the nitrate keeps working for hours. After the last dose of vardenafil, wait at least 24 hours before any nitrate, the same as for sildenafil and half the 48 hours required for tadalafil. If angina strikes before that window closes, withhold the dinitrate: use morphine, oxygen and urgent angiography, with furosemide an option for preload reduction. When choosing an alternative, remember vardenafil's second quirk, QT prolongation: it is not combined with class IA and III antiarrhythmics (quinidine, procainamide, amiodarone, sotalol).
Sources
Mechanism
Same pharmacodynamics – synergistic hypotension.
Symptoms
Fatal hypotension.
Management
Combination contraindicated. 24-hour washout.
Sources
Mechanism
Same as tadalafil-nitrate.
Symptoms
Fatal hypotension.
Management
Combination contraindicated. 24-hour washout.
Sources
Mechanism
Ritonavir – CYP3A4 inhibitor. Vardenafil rises 13-fold.
Symptoms
Severe hypotension, QT prolongation.
Management
Combination contraindicated.
Sources
Verbatim lines from the interaction sections, in the language of the label
«CONTRAINDICATIONS: Administration with nitrates and nitric oxide donors ( 2.4 , 4.1 )»FDA, section 4 · Open on DailyMed
«La administración concomitante de vardenafilo con nitratos o con los que liberan óxido nítrico (como el nitrito de amilo) en cualquiera de sus formas está contraindicada (ver sección 4.5 y sección…»AEMPS, section 4.3 · Open on CIMA
«Estudios in vivo: En un estudio en 18 varones sanos, al administrar vardenafilo (10 mg) a diferentes intervalos de tiempo (entre 1 h y 24 h) antes de una dosis sublingual de nitroglicerina (0.4 mg)…»AEMPS, section 4.5 · Open on CIMA
«Potential for Pharmacodynamic Interactions with Vardenafil: Concomitant use of vardenafil and nitrates and nitric oxide donors is contraindicated. The blood pressure lowering effects of sublingual…»FDA, section 7 · Open on DailyMed
«La administración conjunta de inhibidores de la PDE5, incluyendo vardenafilo, con estimuladores de la guanilato ciclasa, como riociguat, está contraindicada ya que puede producir hipotensión…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Administration with guanylate cyclase (GC) stimulators, such as riociguat ( 2.4 , 4.2 )»FDA, section 4 · Open on DailyMed
«Está contraindicado el uso concomitante de vardenafilo con los inhibidores de la proteasa del VIH, como ritonavir e indinavir, ya que son inhibidores muy potentes del CYP3A4 (ver sección 4.5).»AEMPS, section 4.3 · Open on CIMA
«Efectos en el intervalo QTc: Se desconoce la relevancia clínica de este hallazgo y no puede generalizarse a todo tipo de pacientes en cualquier circunstancia, ya que dependerá de los factores de…»AEMPS, section 4.4 · Open on CIMA
«Effect of Other Drugs on Vardenafil: Erythromycin (500 mg t.i.d.) produced a 4-fold increase in vardenafil AUC and a 3-fold increase in C max when coadministered with vardenafil 5 mg in healthy…»FDA, section 7 · Open on DailyMed
«Está contraindicado el uso concomitante de vardenafilo con los inhibidores potentes del CYP3A4 ketoconazol e itraconazol (en su forma oral) en hombres de más de 75 años.»AEMPS, section 4.3 · Open on CIMA
«Está contraindicado el uso concomitante de vardenafilo con los inhibidores potentes del CYP3A4 ketoconazol e itraconazol (en su forma oral) en hombres de más de 75 años.»AEMPS, section 4.3 · Open on CIMA
«Está contraindicado el uso concomitante de vardenafilo con los inhibidores potentes del CYP3A4 ketoconazol e itraconazol (en su forma oral) en hombres de más de 75 años.»AEMPS, section 4.3 · Open on CIMA
«Efectos en el intervalo QTc: Se desconoce la relevancia clínica de este hallazgo y no puede generalizarse a todo tipo de pacientes en cualquier circunstancia, ya que dependerá de los factores de…»AEMPS, section 4.4 · Open on CIMA
«Effect of Other Drugs on Vardenafil: Ritonavir (600 mg b.i.d.) co-administered with vardenafil 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13fold increase in vardenafil C max . The…»FDA, section 7 · Open on DailyMed
«Efectos en el intervalo QTc: Se desconoce la relevancia clínica de este hallazgo y no puede generalizarse a todo tipo de pacientes en cualquier circunstancia, ya que dependerá de los factores de…»AEMPS, section 4.4 · Open on CIMA
«Efectos en el intervalo QTc: Se desconoce la relevancia clínica de este hallazgo y no puede generalizarse a todo tipo de pacientes en cualquier circunstancia, ya que dependerá de los factores de…»AEMPS, section 4.4 · Open on CIMA
«Estudios in vivo: La administración concomitante de eritromicina (500 mg tres veces al día), un inhibidor del CYP3A4, con vardenafilo (5 mg) produjo un incremento de 4 veces en el AUC de vardenafilo…»AEMPS, section 4.5 · Open on CIMA
«Effect of Other Drugs on Vardenafil: Ritonavir (600 mg b.i.d.) co-administered with vardenafil 5 mg resulted in a 49-fold increase in vardenafil AUC and a 13fold increase in vardenafil C max . The…»FDA, section 7 · Open on DailyMed
«Estudios in vivo: La administración concomitante de eritromicina (500 mg tres veces al día), un inhibidor del CYP3A4, con vardenafilo (5 mg) produjo un incremento de 4 veces en el AUC de vardenafilo…»AEMPS, section 4.5 · Open on CIMA
«Efectos en el intervalo QTc: Se desconoce la relevancia clínica de este hallazgo y no puede generalizarse a todo tipo de pacientes en cualquier circunstancia, ya que dependerá de los factores de…»AEMPS, section 4.4 · Open on CIMA
«Estudios in vivo: Por ello, el tratamiento concomitante sólo debe iniciarse si el paciente está estabilizado con su tratamiento alfabloqueante. En los pacientes estabilizados con el tratamiento…»AEMPS, section 4.5 · Open on CIMA
«Potential for Pharmacodynamic Interactions with Vardenafil: Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. PDE5 inhibitors, including vardenafil and alpha-adrenergic…»FDA, section 7 · Open on DailyMed
«Estudios in vivo: Aunque no se han realizado estudios de interacción específica con todos los medicamentos posibles, el análisis de los datos farmacocinéticos no mostró ningún efecto sobre la…»AEMPS, section 4.5 · Open on CIMA
«Effect of Other Drugs on Vardenafil: No pharmacokinetic interactions were observed between vardenafil and the following drugs: glyburide, warfarin, digoxin, an antacid based on magnesium-aluminum…»FDA, section 7 · Open on DailyMed
«Estudios in vivo: La farmacocinética de vardenafilo (20 mg) no se vio afectada por la administración conjunta con el antagonista H 2 , ranitidina (150 mg dos veces al día), digoxina, warfarina…»AEMPS, section 4.5 · Open on CIMA
«Estudios in vivo: Aunque no se han realizado estudios de interacción específica con todos los medicamentos posibles, el análisis de los datos farmacocinéticos no mostró ningún efecto sobre la…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: Do not use isosorbide dinitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil…»FDA, section 4 · Open on DailyMed
«CONTRAINDICATIONS: Do not use isosorbide mononitrate in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil…»FDA, section 4 · Open on DailyMed
«Uso concomitante de inhibidores de la fosfodiesterasa tipo 5 (PDE5), como el sildenafilo, tadalafilo, vardenafilo,ya que pueden potenciar el efecto vasodilatador de Cordiplast, provocando una…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Use of phosphodiesterase type 5 (PDE-5) inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil, or soluble guanylate cyclase (sGC) stimulators. ( 4.1 , 7.1 )»FDA, section 4 · Open on DailyMed
«Phosphodiesterase Inhibitors: Concomitant administration of Adempas with specific PDE-5 inhibitors (such as sildenafil, tadalafil, or vardenafil) or nonspecific PDE-5 inhibitors (such as dipyridamole…»FDA, section 4 · Open on DailyMed
«Inhibidores de la fosfodiesterasa: Está contraindicado el uso concomitante de vardenafilo con ritonavir (ver sección 4.3)»AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: PDE5 inhibitors: sildenafil, tadalafil, vardenafil ↑ sildenafil ↑ tadalafil ↑ vardenafil Coadministration with atazanavir has not been…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Sildenafil Tadalafil Vardenafil Use With Caution Sildenafil, Tadalafil, Vardenafil: Each of these phosphodiesterase inhibitors is primarily metabolized by CYP3A, and CYP3A will be…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Interactions: Phosphodiesterase-5 (PDE-5) Inhibitors: avanafil sildenafil tadalafil vardenafil ↑ PDE-5 inhibitors Coadministration with avanafil is not…»FDA, section 7 · Open on DailyMed
«INHIBIDORES DE LA FOSFODIESTERASA 5 (PDE-5): La combinación de avanafilo y darunavir potenciado está contraindicada (ver sección 4.3). La administración simultánea de otros inhibidores de PDE-5 para…»AEMPS, section 4.5 · Open on CIMA
«Established and Other Potentially Significant Drug Interactions: PDE-5 inhibitors : e.g. avanafil, sildenafil, tadalafil, vardenafil PDE-5 inhibitors (only the use of sildenafil at doses used for…»FDA, section 7 · Open on DailyMed
«Established and Other Potentially Significant Drug Interactions: PDE5 Inhibitors: avanafil sildenafil, tadalafil, vardenafil ↑ avanafil ↑ sildenafil ↑ tadalafil ↑ vardenafil Sildenafil when used for…»FDA, section 7 · Open on DailyMed
«Sildenafilo, tadalafilo y vardenafilo: Cada uno de estos inhibidores de fosfodiestearasa es metabolizado, al menos en parte, por CYP3A, y CYP3A se puede inhibir con la administración concomitante con…»AEMPS, section 4.5 · Open on CIMA
«Uso con inhibidores de la PDE-5 : La administración concomitante de doxazosina con inhibidores de la fosfodiesterasa-5 (p.ej. sildenafilo, tadalafilo y vardenafilo) debe realizarse con precaución…»AEMPS, section 4.4 · Open on CIMA
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Vardenafil is evaluated for the following indications with varying evidence strength: Erectile dysfunction (evidence tier A), Athletic endurance (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Vardenafil (≥ 1 in 100): Headache, Facial flushing, Nasal congestion, Dyspepsia, Dizziness. See the Safety section for uncommon and serious reactions.
Not used in women.
Not used in women.
Vardenafil is contraindicated in: Combination with any nitrate or NO donor; Combination with riociguat; Prior QT prolongation; Class IA and III antiarrhythmics (amiodarone, quinidine, sotalol); Severe hepatic impairment. Full list in the Safety section.
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Dutasteride, Dutasteride + Tamsulosin, Fesoterodine, Finasteride, Propiverine, Sildenafil, Tadalafil, Mirabegron