ED medications compared: sildenafil, tadalafil, vardenafil and avanafil

Four prescription ED medications are available in the Netherlands: sildenafil, tadalafil, vardenafil and avanafil. All four work through the same mechanism. The difference is how fast they start and how long they last.

That difference usually decides which one suits you. Around 30 to 35 percent of men get too little effect from the first pill they try, and that is often not the medicine's fault.

One thing stands out in the Dutch search results: nearly every comparison sits on a site that also sells the pills. So here they are side by side, with no shop attached.

How do ED medications actually work?

All four are PDE5 inhibitors. They block an enzyme that lets the blood vessels in the penis contract again. That keeps the erectile tissue filled with blood for longer. A pill does not create an erection by itself, because you still need sexual stimulation.

That last point is the most commonly missed detail. Men who expect something to happen on its own conclude after half an hour that the medicine failed.

The four differ mainly in how long they stay in your body. Sildenafil has a half-life of roughly 4 hours, tadalafil roughly 17.5 hours. Those numbers come from the Dutch Farmacotherapeutisch Kompas and explain almost every practical difference.

The four ED medications side by side

Below are the four active substances with their best known brand name, how quickly they usually work and how long the effect lasts. These figures come from the patient leaflets and the Farmacotherapeutisch Kompas. Your doctor decides which medicine and which strength fit your situation.

Avanafil is the fastest of the four. Tadalafil lasts by far the longest, which earned it the nickname weekend pill.

Which ED medication fits which situation?

The choice is rarely about which medicine is stronger. A 2026 network meta-analysis found that PDE5 inhibitors differ mainly in profile, not in whether they work. The practical question is whether you need to plan ahead or not.

Take two men aged 46. One has a steady partner and usually has sex at the weekend, spread across two days. For him a medicine that lasts 36 hours beats a pill he has to time each occasion.

The other has sex two or three times a month, usually unplanned. For him a short-acting medicine that works within half an hour makes more sense.

Both have the same problem. The answer differs purely because of their calendar.

What if an ED medication does not work?

Roughly 30 to 35 percent of men respond poorly to a PDE5 inhibitor. That does not automatically mean pills are useless for you. Something else is often involved: too little stimulation, too low a dose, or an underlying cause nobody has looked at yet.

Research describes that some men who do not respond to sildenafil have low testosterone. In men with diabetes, older research found the response improved once the testosterone deficiency was addressed. That is no guarantee, but it does make blood values a sensible place to look.

Your blood sugar and blood vessels matter too. We wrote earlier about the link between blood sugar and your erection and about the signals of low testosterone.

A testosterone test can bring some of those values into view. What your result means is a conversation for your GP.

Which side effects come with every PDE5 inhibitor?

The side effects look very similar, because the medicines do the same thing. Headache, flushing, a blocked nose, stomach complaints and back pain are the most common. They are usually mild and fade as the medicine wears off.

There is one exception that tolerates no nuance. Combining these medicines with nitrates, for example nitroglycerin for heart complaints or poppers, can drop your blood pressure dangerously. That combination should never happen.

Rare but urgent is an erection that will not go away. We covered that separately in our article on priapism.

The emphasis differs per medicine. More on that in the side effects of sildenafil and those of tadalafil.

Can you get ED medication without a prescription?

No. All four ED medications require a prescription in the Netherlands. Your GP first looks at your heart, your blood pressure and your other medication, precisely because of that nitrate interaction.

Even so, a large share of ED pills used in the Netherlands comes from the illegal market. Based on wastewater research by the Dutch public health institute RIVM, broadcaster NOS estimated in 2017 that around 150,000 men use ED pills while roughly 45,000 had a prescription.

That gap is enormous. We discuss the risks in our article on Kamagra.

What you can discuss with your GP

I notice men put this conversation off for months and then find it shorter than expected. It covers your heart, your blood pressure and your medication. We described how it goes in this article about seeing your GP.

Bring which medicine you already tried, at which strength, how often, and whether you had been drinking or eating a heavy meal. Those four details change the conversation immediately.

And if erection problems are new and came on quickly, the heart question matters. In research, erectile dysfunction regularly shows up as an early signal of vascular problems, as we described in blood values and cardiovascular disease. Desire plays its own separate role, which we cover in the article on libido and hormones.

If your issue is finishing too quickly rather than the erection itself, read the article on dapoxetine. And for a curve that changes within weeks, Peyronie disease is a separate diagnosis.

Every blood test result includes a professional assessment from a BIG-registered doctor. For treatment decisions, discuss your results with your GP.

References

• Tienforti D, et al. Comparative evaluation of on-demand PDE5 inhibitor efficacy in erectile dysfunction. J Sex Med, 2026. PMID: 42296271
• Gong B, et al. Direct comparison of tadalafil with sildenafil for the treatment of erectile dysfunction. Int Urol Nephrol, 2017. PMID: 28741090
• Yafi FA, et al. Non-invasive management options for erectile dysfunction when a phosphodiesterase type 5 inhibitor fails. Drugs Aging, 2018. PMID: 29464656
• Farmacotherapeutisch Kompas, monographs for sildenafil, tadalafil, vardenafil and avanafil.
• RIVM wastewater research on ED medication, via NOS, 13 May 2017.