Viagra, Cialis, Levitra, Spedra: are there differences in terms of efficacy, speed of action and duration of the therapeutic effect?

Viagra, Cialis, Levitra and Spedra are drugs belonging to the family of 5-phospho-diesterase (5PDE) enzyme inhibitors. These well-known “trade names” correspond to 4 different active ingredients: sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra) and avanafil (Spedra).

These drugs have proven to be effective in promoting penile erection and have truly revolutionized the medical treatment of erectile dysfunction. Let’s try to understand if there are substantial differences between these 4 drugs in terms of efficacy, how to take them, the speed of onset of pharmacological action and the duration of the therapeutic effect. The evaluation of side effects and contra-indications is instead covered in a separate article (which can be found at this link).

Erection is basically supported by an increase in blood flow within the corpora cavernosa of the penis. It is actually a complex phenomenon that requires the integrity – in addition to the vascular system – of the nervous system and penile anatomical structures and is affected by psychological and hormonal aspects. A problem in one of these areas can lead to erectile dysfunction. Impotence is classified on the basis of the triggering cause into vasculogenic, neurogenic, psychogenic, hormonal, etc.

Treatment of erectile dysfunction should be – whenever possible – directly aimed at resolving the cause. Since in clinical reality this can only be done in limited cases – as the causes are often not easily recognizable or multi-factorial – a medical therapy aimed at eliminating the disorder (the symptom) can be resorted to, regardless of the cause that generated it: this symptomatic pharmacological therapy is based on the use of 5PDE inhibitor drugs. It is therefore essential that these drugs are always and only used after careful medical evaluation aimed at identifying any resolvable causes of impotence.

The mechanism of action:

One of the fundamental chemical mediators for erection is nitric oxide (NO). This molecule is able to initiate a complex chain of chemical reactions that ultimately leads to the relaxation of the smooth muscle cells of the penile vessels. The relaxation of the vessel wall determines the vaso-dilation necessary to facilitate the flow of blood to the penis. The drugs in question are able to inhibit a specific enzyme (5-phospho-dyesterase) involved in the degradation of one of the chemical mediators involved in this chain.

Nitric oxide is released from nerve endings located in the penis as a result of sexual stimulation. Since 5PDE inhibitor drugs can prolong the effect of nitric oxide but not its “secretion”, It is clear that the action on erection of these drugs cannot be separated from sexual stimulation. Viagra, Cialis, Levitra and Spedra are therefore not capable of causing spontaneous erections: If there is no sexual intercourse in the penis after taking them, no change is observed.

Therapeutic efficacy:

Drug therapy is defined as effective when it is able to determine the appearance of an erection sufficient for penetration. All 4 drugs in question – in the studies in which they were tested – demonstrated a very high efficacy ranging from 60 to 90% of cases in relation to the severity of erectile dysfunction. To date, there are no serious scientific studies that have compared the effectiveness of one of these drugs compared to the others. In general, considering large patient populations, it seems that the efficacy is similar and there is no one drug that is more effective than the others. However, in the individual patient, it may happen that one drug gives better results than another and it may therefore be convenient to try more drugs when the answer is not completely satisfactory.

Speed of action:

As far as the speed of the onset of the therapeutic effect is concerned, however, there are important differences between the various drugs in question. In the case of sildenafil (Viagra), the effect begins about 30 minutes after intake, and the peak of therapeutic efficacy occurs after another 30 minutes. It is therefore advisable to take sildenafil about 1 hour before sexual intercourse. The speed of action of vardenafil (Levitra) is very similar to that of sildenafil and therefore the same recommendations apply.

Avanafil (Spedra) differs in that the therapeutic effect appears more quickly: It starts as early as 15 minutes after intake and peaks in effectiveness at 30 minutes. This feature makes the Spedra particularly suitable for unplanned and “last-minute” sexual intercourse: It is enough to “temporize” for about half an hour – possibly dedicating yourself to foreplay (!) – before starting the penetrative act.

In contrast, tadalafil (Cialis) is the slowest of the 5PDE-inhibiting drugs: Although the therapeutic action begins to manifest itself after 30-40 minutes of intake, its peak is reached only at 2 hours. This means that it is advisable to start sexual intercourse no earlier than two hours after taking the medication.

When speed of action is a very important aspect for the patient, the use of orodispersible / orodispersible formulations of 5PDE inhibitor drugs can be considered. These preparations dissolve in a short time inside the mouth and are directly absorbed by the mucous membranes and released into the circulation (thus skipping the steps of gastric absorption and portal circulation). On the market there is orodispersible Levitra and some preparations containing sildenafil formed by thin orodispersible films (they can be found in pharmacies under the names of Siler and Rabestrom and have been the subject of a dedicated article that you can find at this link).

Duration of therapeutic effect:

If we analyze the duration of therapeutic action of the 4 drugs in question, we see that tadalafil (Cialis) is the undisputed winner: In fact, its therapeutic effect reaches up to about 36 hours (!) from intake and – for this characteristic – it has “earned” the nickname of “weekend pill“. To assess the duration of action of a drug, reference is usually made to its “half-life” (T/2), which corresponds to the time it takes for the body to eliminate half of the drug in circulation. The half-life of cialis is 17 hours and is considerably higher than that of other 5PDE inhibitors: viagra and levitra have a half-life of about 3 hours while that of spedra reaches 6 hours.

On-demand or continuous recruitment?

The typical use of these drugs is defined as “on demand“: They are only taken when sexual intercourse is planned. Only tadalafil (Cialis) – due to its pharmacokinetic properties – can be used continuously. Taking advantage of the fact that its therapeutic effect is more than 24 hours – cialis can be taken daily (at a lower dosage than that provided for on-demand use) in order to guarantee a “permanent” therapeutic efficacy throughout the day. This continuous intake is advisable in patients who have frequent sexual intercourse and has the considerable advantage of living a more “natural” sexuality: in fact, it is not necessary to “schedule” sexual intercourse since the drug is always active. The disadvantage of this type of therapy is only economic.

Can the effectiveness be affected by food and alcohol?

It is good to know that 5PDE inhibitor drugs can be significantly less effective when taken together or immediately after a meal, especially when the food is high in fat and accompanied by alcoholic beverages. This is especially true for sildenafil (Viagra) and vardenafil (Levitra): these drugs – in order not to compromise their effectiveness – must be taken between meals! The one that is least affected by food and alcohol is tadalafil (Cialis).

Conclusions and comparative table:

5PDE inhibitor drugs are all highly effective: In general, there is no one drug that is more effective than the others, although each individual patient may experience different results depending on the drug used. The most important differences are the speed of action and the duration of the effect. Avanafil (Spedra) was found to be the fastest drug to achieve therapeutic efficacy and can be taken as little as 30 minutes before intercourse. Tadalafil (Cialis), on the other hand, stands out for the high duration of the pharmacological effect, so much so that it can also be used in continuous daily therapy and not only on demand (as is the case with other drugs). Taking the medication in conjunction with food and alcohol can cause a noticeable reduction in therapeutic efficacy. This is especially true for sildenafil (Viagra) and vardenafil (Levitra).