Comparison of efficacy and side effects of Sildenafil, Vardenafil and Tadalafil for the treatment of Erectile Dysfunction

Review of the Literature

Since the appearance of Sildenafil in the pharmaceutical market, back in 1998, the treatment of erectile dysfunction changed radically. Obsolete and traumatic treatments such as intraurethral or intracavernosal injections or penile implants have been practically abandoned.

These oral treatments have given new hope to the many patients who have erectile dysfunction, regardless of the cause. It is estimated that 1 in 5 men experience some degree of erectile dysfunction, especially after 50 years of age.

The first molecule described in this group, Sildenafil, has been widely studied, and its pharmacokinetic and pharmacodynamic behavior, as well as its adverse effects and efficacy, are well known at present. Two other drugs have shown up in this group of phosphodiesterase 5 inhibitors: Vardenafil, with pharmacological characteristics very similar to those of Sildenafil, and Tadalafil, which differs considerably in its structure and therefore also in pharmacokinetics.

Given these new alternatives, the usual questions arise regarding efficiency and adverse effects. Therefore, the need to review the extensive scientific literature produced around this new range of enhancement pills.

We are going to write a summary of this review article here: Erectile dysfunction: comparison of efficacy and side effects of the PDE-5 inhibitors sildenafil, vardenafil and tadalafil–review of the literature.



Gresser and Gleiter, two German researchers, undertook the task of compiling and reviewing several articles published in different scientific journals since the appearance of the PDE-5 inhibitors in 1998 and 2002, the year in which this review was carried out.

They also made a summary of the physiological and physiopathological events that surround the erection and its disorders, including the biochemical and neurological processes that are involved.

Erectile Dysfunction

They assume the definition of Erectile Dysfunction accepted internationally by the National Institute of Health as the persistent inability of a man to achieve and / or maintain an erection sufficient for satisfactory sexual performance. This can be classified according to its etiology (organic and psychogenic) or severity (mild, moderate and severe).


During the review, different causes of erectile dysfunction are considered, as mentioned in the previous section, with cardiovascular diseases being the main risk factor. According to some studies, 20% of patients with erectile dysfunction have diabetes, 30% are hypertensive, 30% are smokers, and 38% are habitual consumers of alcohol.

Mechanism of Action

A detailed review of the effects of PDE-5 inhibitors is also described. It can be summarized that these drugs favor the release of Nitric Oxide, a potent vasodilator, which acts on the blood vessels of the penis, allowing the entry of blood and erection after sexual stimulation. They also inhibit the metabolism of the aforementioned Nitric Oxide, so that its vasodilator effect is prolonged over time, restoring the ability of man to achieve a satisfactory erection.

Potency and Selectivity

Going into the subject, several aspects of the PDE-5 inhibitors were evaluated, including potency and selectivity. This is important because phosphodiesterases, a family of enzymes that regulate multiple cellular functions, do not only participate in the physiology of the erection but are distributed throughout the body performing different tasks.

Unfortunately, potency studies have shown very different results, but what seems obvious is that sildenafil is the least powerful of all, so higher doses are required to achieve the expected effects, and adverse events could be more accentuated with this medicine.

The selectivity studies were not too clear either, but none showed significant differences between the different PDE-5 inhibitors. The only important finding was related to FDE-6, which acts at the ocular level and FDE-11. Here, Sildenafil and Vardenafil showed less selectivity than Tadalafil, which could cause some clinical adverse effects, but at the time of this review, there was very little information about it.


The three substances are quickly absorbed through the gastrointestinal tract, reaching peak plasma levels after 1 hour for Sildenafil and Vardenafil and after 2 hours for Tadalafil. The consumption of food does not seem to modify the percentage of absorption of any of the three drugs, although it was demonstrated that the taking of these with the empty stomach could accelerate their effect.

The half-life of Sildenafil and Vardenafil is approximately 3 – 4 hours, being much longer in Tadalafil, which can reach up to 18 hours in some men. The metabolization and elimination of the 3 drugs are basically via the liver, through the enzyme cytochrome P-450.

Clinical Experience

The start of action of the 3 drugs occurs in less than half an hour. Some studies indicate that in the case of Sildenafil it can be as early as 12 minutes and 16 minutes after the intake of Tadalafil. Animal models of Vardenafil, show an onset of effect 20 minutes after ingestion.

According to most studies that were available as of the date of this review, all PDE-5 inhibitors are effective. Unfortunately, comparative studies in humans had not been carried out, only individual trials for each drug, so comparing response rates was impossible. The percentage of improvement in the ability to achieve an erection was above 80% for all PDE-5 inhibitors, and when compared to placebo, the difference in effects was overwhelming.

The typical adverse effects of the PDE-5 inhibitors were headache, facial flushing, nasal congestion, and dyspepsia, with similar frequency of occurrence for the 3 drugs evaluated. However, for Vardenafil and Tadalafil, there were not enough studies yet to obtain definitive conclusions.

Changes in vision have been described after the ingestion of Sildenafil and Vardenafil, which do not seem to be permanent or very extensive, and very rarely this effect caused the treatment to be discontinued. The effects of potent inhibition of phosphodiesterase-11 by Tadalafil remained to be seen.

Tolerance of tadalafil was an issue. Between 7% and 29% of patients discontinued treatment due to the presence of adverse effects such as headache, muscle and back pain, and dyspepsia.

Interactions and Contraindications

All PDE-5 inhibitors can potentiate the vasodilatory effect of nitrates, for which their combined use can be dangerous. The dose should be decreased in elderly patients because it has been seen that these drugs are metabolized more slowly in this age group.

Patients at high risk of heart attacks should avoid the use of any of these three drugs since sexual activity is not allowed, as well as patients with some cardiac malformations, orthostatic hypotension, obstructive myocardiopathy or aortic stenosis. Neither should they be consumed by patients with retinitis pigmentosa.


Despite the fact that in 2002 there was still a lack of information, Sildenafil was considered a safe and reliable drug for the treatment of erectile dysfunction. Time would be responsible for demonstrating the same for Vardenafil and Tadalafil.

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