Vardenafil
Phosphodiesterase-5 inhibitors
Phosphodiesterase-5 inhibitors
An oral PDE5 inhibitor for erectile dysfunction; works only with sexual stimulation and must never be combined with nitrates.
Quick facts
- Group
- Phosphodiesterase-5 inhibitors
- Target
- Phosphodiesterase type 5 (cGMP-specific phosphodiesterase)
- Used for
- Erectile dysfunction
- Key effects
- Headache and flushing · Nasal congestion and sinusitis
- Monitor
- Blood pressure · Any change in vision or hearing
- ATC
- G04BE09
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows vardenafil in the catalytic site of human PDE5A (crystal structure).
Sexual stimulation releases nitric oxide in the corpus cavernosum, which activates guanylate cyclase and raises cyclic GMP; cGMP relaxes smooth muscle and blood fills the erectile tissue. PDE5 breaks cGMP down. Vardenafil selectively inhibits PDE5, so cGMP lasts longer and the erection is easier to obtain and keep. Without sexual stimulation there is no nitric oxide release and no effect.
- Sexual stimulation releases nitric oxide in the corpus cavernosum
- Nitric oxide raises cGMP, which relaxes smooth muscle
- Vardenafil blocks PDE5, so cGMP is not broken down
- Blood flow and erection improve; no stimulation, no effect
Indications
- Erectile dysfunction Erectile dysfunction →
Adverse effects
Common
- Headache and flushing
- Nasal congestion and sinusitis
- Dyspepsia and nausea
- Dizziness, back pain and flu-like symptoms
- Transient colour-vision changes
Contraindications
- Nitrates or nitric oxide donors, regular or occasional (including amyl nitrite)
- Guanylate cyclase stimulators such as riociguat
- Men in whom sexual activity is unsafe because of heart disease
- Severe hepatic impairment and renal dialysis
Key interactions
- Nitrates (glyceryl trinitrate, isosorbide mononitrate, isosorbide dinitrate)
- Severe additive fall in blood pressure; contraindicated
- Strong and moderate CYP3A4 inhibitors (ritonavir, ketoconazole, clarithromycin, erythromycin, grapefruit juice)
- Much higher vardenafil levels; dose limits apply
- Alpha-blockers (tamsulosin, doxazosin) and other antihypertensives
- Additive hypotension; the alpha-blocker dose is stable first
- Class IA and III antiarrhythmics (amiodarone)
- Added QT prolongation; avoided
What is monitored
- Blood pressure in patients on antihypertensives or alpha-blockers
- Cardiovascular fitness for sexual activity
- Any change in vision or hearing
Administration and safety
- Oral film-coated tablet or orally disintegrating tablet; the two are not interchangeable
- The orally disintegrating tablet is placed on the tongue without water and contains aspartame (phenylketonuria)
- Taken no more than once a day
Pregnancy and breastfeeding
Not indicated in women.
Nursing care
- Ask about nitrate use, including sublingual nitroglycerin and recreational nitrites, before it is used
- Teach that in chest pain the emergency team must be told about vardenafil use
- Teach to seek urgent care for an erection lasting more than four hours or sudden vision or hearing loss
- Remind that it does not protect against sexually transmitted infections
Pharmacokinetics
- Absorption
- Oral; low absolute bioavailability (about 15%); a high-fat meal lowers the peak
- Distribution
- Highly bound to plasma proteins (about 95%)
- Metabolism
- Liver, mainly CYP3A4 (also CYP3A5 and CYP2C); the main metabolite is weakly active
- Elimination
- Mostly in faeces as metabolites; little in urine
- Half-life
- About 4 to 5 hours
- Onset and duration
- Peak levels in about an hour; it is taken about an hour before sexual activity
Test yourself
Think of the answer, then tap the question to see it.
Why must vardenafil never be combined with nitrates?
Both raise cGMP in vascular smooth muscle, causing a severe, possibly fatal fall in blood pressure.
Why does vardenafil not work without sexual stimulation?
It only prevents cGMP breakdown; cGMP is made only after nitric oxide is released during stimulation.
Which cardiac conduction effect is a labelled warning for vardenafil?
QT prolongation; it is avoided with class IA and III antiarrhythmics and in congenital long QT.
Connections
← Back to the class: Phosphodiesterase-5 inhibitors
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - VARDENAFIL HYDROCHLORIDE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2023); Vardenafil: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 1XP0: Catalytic Domain Of Human Phosphodiesterase 5A In Complex With Vardenafil (RCSB Protein Data Bank, 2004); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.