PDE5 inhibitors are the most familiar medicines for erectile dysfunction. The four main members of the class are avanafil, sildenafil, tadalafil and vardenafil.1 They aren't aphrodisiacs and they don't produce an erection out of nowhere: they amplify the body's own response to arousal.
The name describes the mechanism. During arousal, a chemical messenger called cyclic GMP (cGMP) builds up in the erectile tissue and helps its smooth muscle relax so blood can flow in. An enzyme called phosphodiesterase type 5 (PDE5) breaks cGMP down. Blocking that enzyme lets cGMP persist, which increases the penile response to sexual stimulation.2
Because these drugs widen blood vessels, they also affect blood pressure. That's why they need a prescriber who can check your heart health and your other medicines, above all whether you take nitrates.3
How well do PDE5 inhibitors work?
Well, for most men with erectile dysfunction. In an early sildenafil trial, 69% of attempts at sex were successful on the drug compared with 22% on placebo.
That figure comes from a 12-week trial in men whose ED had physical, psychological or mixed causes.2 Later reviews put the first-time response rate across the class at roughly 60 to 70%.1
A 2013 review found the literature doesn't clearly favour one drug over another. If one doesn't suit you, that's worth raising with your prescriber: success rates were high when men had access to all the available options.1
How do the different PDE5 inhibitors differ?
Mainly in how quickly they act, how long they last and their side-effect profile. Tadalafil stays in the body longest, while avanafil reaches peak levels fastest.
Each drug has its own pharmacokinetic and side-effect profile. Sildenafil is more often associated with visual changes, vardenafil with QT prolongation (a change on the heart's electrical trace) and tadalafil with lower back pain. Avanafil and a mouth-dissolving form of vardenafil reach peak blood levels fastest, while tadalafil has the longest half-life.1
Which one suits you, and in what form, is a decision for you and your prescriber. We don't give dosing advice: the right dose depends on your health, your other medicines and how you respond.
Who shouldn't take PDE5 inhibitors?
Anyone taking nitrate medicines, such as the sprays, tablets or patches used for angina, must not take them. The combination can cause a dangerous drop in blood pressure.
Nitrates and PDE5 inhibitors are both vasodilators, and together their blood-pressure-lowering effects can add up. A 2018 review of the interaction describes organic nitrates as an absolute contraindication, and says men on nitrates who want a PDE5 inhibitor need an individual assessment of whether the nitrate can safely be stopped, which is a decision only their doctors can make.3 The same danger applies to recreational 'poppers' (amyl nitrite): using them alongside PDE5 inhibitors has led to potentially harmful or even fatal interactions.4
This is the core reason PDE5 inhibitors need a prescriber: a clinician should check your heart health, blood pressure and full list of medicines first. If you ever develop chest pain after taking one, tell the emergency team straight away, because it changes which heart treatments are safe to give.3
What are the side effects of PDE5 inhibitors?
The most common are headache, flushing and indigestion. In the early sildenafil trials these affected between 6% and 18% of men.
In the sildenafil trials, headache, flushing and dyspepsia (indigestion) were the most commonly reported adverse effects, and 92% of men who entered the 32-week open-label extension completed it.2 Visual changes and back pain are associated with particular drugs in the class.1
Seek urgent help for chest pain, a painful erection that won't go down, or any sudden change in your vision. And avoid websites that skip the medical questions: you lose the safety check that makes these medicines appropriate in the first place.
Common questions
Do PDE5 inhibitors work without arousal?
No. They increase the penile response to sexual stimulation rather than causing an erection on their own.2 Without arousal, not much happens.
Do I need a prescriber for PDE5 inhibitors?
Yes, treat them as medicines that need a prescriber. A clinician should check your heart health, blood pressure and other medicines, especially nitrates, before you take one.3 It's also a chance to look for the cause of the erection problem; see our erectile dysfunction entry.
Is one PDE5 inhibitor better than another?
Not clearly. Reviews find similar first-time response rates across the class, and the literature doesn't clearly favour one over another.1 The choice usually comes down to timing, duration and side effects.
Read more on this
Does cardio really improve erections? What the research says
How stress affects erections and libido
Sources
- Smith WB 2nd, et al. PDE5 inhibitors: considerations for preference and long-term adherence. Int J Clin Pract. 2013;67(8):768-80. PubMed
- Goldstein I, et al. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med. 1998;338(20):1397-404. PubMed
- Kloner RA, et al. A New Perspective on the Nitrate-Phosphodiesterase Type 5 Inhibitor Interaction. J Cardiovasc Pharmacol Ther. 2018;23(5):375-386. PubMed
- Smith KM, Romanelli F. Recreational use and misuse of phosphodiesterase 5 inhibitors. J Am Pharm Assoc (2003). 2005;45(1):63-72. PubMed
Not medical advice. Written by Eric Stephens from the research cited above; not reviewed by a doctor. If something worries you, see a GP.