If you’ve read our sildenafil vs tadalafil comparison, you already know the two most popular ED medications inside and out. But the PDE5 inhibitor family actually has four members, and the other two — avanafil (Stendra) and vardenafil (Levitra) — offer advantages that make them the better choice for certain patients. Here’s the complete picture.
How PDE5 Inhibitors Work
All four medications work through the same fundamental mechanism: they block phosphodiesterase type 5, an enzyme that breaks down cGMP in the smooth muscle of the penis. By inhibiting PDE5, these drugs allow cGMP to accumulate, promoting blood vessel dilation and enabling an erection in response to sexual stimulation. They don’t create arousal — they make it physically possible when arousal is present.
The differences between them come down to pharmacokinetics: how quickly they start working, how long they last, how food affects absorption, and their side effect profiles.
The Complete Comparison
| Feature | Sildenafil (Viagra) | Tadalafil (Cialis) | Avanafil (Stendra) | Vardenafil (Levitra) |
|---|---|---|---|---|
| Onset | 30–60 min | 30–45 min | 15–30 min | 25–60 min |
| Duration | 4–6 hours | Up to 36 hours | 6–12 hours | 4–5 hours |
| Food effect | High-fat meals delay it | Minimal | Minimal | High-fat meals delay it |
| Daily dosing option | No | Yes (2.5–5mg) | No | No |
| Common side effects | Headache, flushing, visual changes | Headache, back pain, muscle aches | Headache, flushing (milder) | Headache, flushing, nasal congestion |
| Typical cost (generic) | $1–$8/pill | $1–$10/pill | $15–$40/pill | $8–$20/pill |
Avanafil: The Speed Champion
Avanafil (brand name Stendra) is the newest PDE5 inhibitor and the fastest-acting. Some men report effectiveness within 15 minutes, making it ideal for spontaneous situations. It also has the most selective PDE5 inhibition of the group, which translates to fewer side effects overall — particularly fewer visual disturbances and less facial flushing than sildenafil.
The tradeoff: avanafil is the most expensive option because no widely available generic exists yet. If cost is a factor, it’s not the first-line choice. But for men who experience significant side effects on sildenafil or who want the fastest possible onset, it’s worth discussing with a telehealth provider.
Vardenafil: The Underrated Option
Vardenafil (Levitra) is pharmacologically similar to sildenafil but with slightly different selectivity. It’s considered by some clinicians to be more potent milligram-for-milligram, meaning a lower dose can produce the same effect. It also comes in an orally disintegrating tablet (ODT) formulation that dissolves on the tongue — useful for men who have difficulty swallowing pills or who want a faster onset without water.
Like sildenafil, vardenafil’s absorption is affected by high-fat meals. Its duration is comparable to sildenafil at 4-5 hours. It’s a solid middle-ground option that deserves more attention than it gets.
Which Should You Choose?
For spontaneity and long duration: Tadalafil. Its 36-hour window means you don’t have to plan around a pill, and the daily dosing option eliminates timing concerns entirely.
For fastest onset: Avanafil. If 15-minute onset time matters to you and cost isn’t a barrier, it’s the quickest option.
For lowest cost: Sildenafil. Generic sildenafil is widely available and extremely affordable through telehealth platforms.
For men who get side effects from sildenafil: Try avanafil (fewer sides) or tadalafil (different side effect profile — back/muscle pain instead of flushing/visual changes).
For men who need a low dose: Vardenafil may be effective at lower doses than sildenafil for some patients.
Important: All four PDE5 inhibitors are contraindicated with nitrate medications (nitroglycerin, isosorbide). If you take nitrates for heart conditions, these drugs are not safe for you.
For men exploring their options, our complete guide to getting ED treatment online walks through the telehealth consultation process step by step.
Compare telehealth providers offering all four ED medications — with licensed physicians, discreet shipping, and transparent pricing.
Compare Providers →When One Medication Isn’t Enough
If you’ve tried one PDE5 inhibitor without adequate results, don’t give up. Switching to a different one often works — the selectivity differences mean your body may respond better to one over another. And for men who don’t respond adequately to any single PDE5 inhibitor, our article on combination ED therapy covers what comes next.