Sildenafil and Tadalafil: Why the First Attempts Often Fail

A man who takes sildenafil once, with dinner, at the lowest dose, and gets a poor result often concludes the drug does not work for him. Most of those early failures come down to food, timing, stimulation or dose.

Sildenafil and tadalafil are PDE5 inhibitors. They are effective for most men with erectile dysfunction, but they depend on conditions the user controls. The 2018 American Urological Association guideline gives two of its strongest recommendations to this point: men should be told how to take the medication properly, and the dose should be adjusted until it works. One low dose taken under the wrong conditions is not an adequate trial.

How the drugs work

Sexual arousal releases nitric oxide from nerves and blood vessel lining in the penis. Nitric oxide raises a messenger molecule called cGMP, which relaxes the smooth muscle in the arteries and the erectile tissue. Blood flows in and the tissue expands.

PDE5 is the enzyme that breaks cGMP down. Blocking it lets cGMP build up, so the relaxation signal is stronger and lasts longer. The drug amplifies a signal that arousal starts. Without arousal there is little cGMP to protect, and little happens.

The common reasons for a poor result

No stimulation

Taking the tablet and waiting for an erection to appear does not work. Physical and mental stimulation are needed to start the process the drug then supports.

Food, particularly fat

A heavy or high-fat meal slows the absorption of sildenafil and delays its effect. Taking it straight after a large dinner is one of the most common reasons for a disappointing first attempt. Tadalafil absorption is not significantly affected by food.

Timing

Sildenafil usually needs 30 to 60 minutes to take effect, longer after food, and the useful window is several hours. Tadalafil takes longer to reach its peak but lasts much longer, often into the next day. Taking either drug immediately before sex leaves too little time.

Dose

Many men start on a low dose and never move up. Dose titration is part of the treatment. A prescriber can increase the dose if the first one is tolerated but not sufficient.

Too few attempts

In a pooled analysis of 1,276 men taking sildenafil, the cumulative chance of successful intercourse kept increasing with each attempt and leveled off after about eight. Anxiety about whether the pill will work, a new situation, or tiredness can all affect a single attempt.

One study of 100 men referred as sildenafil non-responders found that more than half had used the drug incorrectly. Many had never tried the highest dose, a third had taken it straight after a full meal, and some did not know that stimulation was necessary.

Sildenafil or tadalafil?

Both drugs work in the same way and have similar overall effectiveness. They differ mainly in timing.

• Sildenafil acts for several hours. It suits men who prefer to take a tablet on specific occasions and do not mind planning around meals.
• Tadalafil lasts much longer and is unaffected by food. It suits men who prefer less planning. It is also available as a low daily dose, which removes the need to time a tablet at all.

Side effects are similar: headache, flushing, nasal congestion and indigestion are the most common. Tadalafil can also cause back and muscle aches.

Safety

Never combine a PDE5 inhibitor with nitrates. Nitroglycerin and other nitrate medications for angina, including recreational amyl nitrite, can combine with these drugs to lower blood pressure dangerously. Tell any emergency clinician if you have taken sildenafil or tadalafil, because it affects which chest pain treatments are safe.

Alpha-blockers used for prostate symptoms and high blood pressure can also add to the blood pressure effect. A prescriber should know about every medication you take.

When the drug works only partly

Some men follow every instruction, reach the full dose, try it many times, and still get an erection that forms and then fades. That usually means inflow improved while venous retention did not.

PDE5 inhibitors act on the inflow side. They relax the arteries and the erectile tissue so blood enters easily. Holding the erection depends on the expanding tissue compressing the draining veins. When that compression is incomplete, blood leaves as fast as it arrives. This is venous leak, and it is a common reason tablets give a partial result. Our article on venous leak and erectile dysfunction covers it in detail.

Xialla slows venous outflow at the base of the penis, and its anchoring strap keeps it in position during intercourse. Many men use it together with a PDE5 inhibitor, one for inflow and one for retention. Xialla does not produce an erection, does not treat the underlying cause of venous leak, and does not help where the problem is poor arterial inflow alone. Follow the wear-time limits in our guide to using a constriction device safely.

Before concluding the drug has failed

• Take it on an empty stomach or after a light meal if using sildenafil.
• Allow enough time before sex.
• Make sure there is sexual stimulation.
• Ask your prescriber about increasing the dose.
• Try it on several occasions, not one or two.
• If erections form but fade, describe that pattern to your doctor, because it points to a retention problem.

Our article on the full range of options in the AUA guideline covers what comes next if tablets are not enough.

Related reading

• Beyond Pills: Understanding the Full Spectrum of ED Options in the 2018 AUA Guideline
• Venous Leak and Erectile Dysfunction Explained
• Medications That Affect Erections: What the Evidence Shows and What to Ask Your Doctor
• Alcohol and Erectile Function: Acute Effects and Long-Term Damage

References

• Burnett AL, Nehra A, Breau RH, et al. Erectile Dysfunction: AUA Guideline. Journal of Urology. 2018;200(3):633-641. Statements 9 and 10. AUA Guidelines page
• McCullough AR, Barada JH, Fawzy A, Guay AT, Hatzichristou D. Achieving treatment optimization with sildenafil citrate (Viagra) in patients with erectile dysfunction. Urology. 2002;60(Suppl 2B):28-38. https://doi.org/10.1016/S0090-4295(02)01688-6

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