The most common medications used to treat erectile dysfunction (ED) are Viagra, Cialis, Sildenafil, and Levitra. They belong to a class of drugs called phosphodiesterase 5 inhibitors (PDE5 inhibitors), which will be explained below.

Before comparing the medications, it is important to know how an erection is achieved and how the medications used to treat ED help men achieve and maintain erections sufficient for sexual activity.

An erection occurs when someone is stimulated by an erotic thought or sexual contact. The brain then commands nitric oxide be produced. That leads to a series of chemical reactions in the blood vessels of the penis that results in 6 times the blood flow getting trapped in the penis. An erection might last indefinitely if it weren’t for chemicals called phosphodiesterases. They work at reversing the process that keeps the penis erect.

Usually there is a balance between the chemicals that cause an erection and those that would return the penis to being flaccid. They pull in opposite directions with one dominating over the other in a perfect sequence that lets a man have an erection as long as it is needed. That balance makes sure the phosphodiesterases to do their job when they should, but no sooner.

ED medications interfere with the chemicals that allow blood to leave the penis. They push the balance in favor of an erection. Men with erectile dysfunction benefit from having the chemicals leading to the erection outweigh the actions of the phosphodiesterases that cause the penis to lose its firmness. That is exactly what the medications for erectile dysfunction do; they block, or inhibit, the phosphodiesterases (that’s why they are called phosphodiesterase inhibitors). Simply stated, erectile dysfunction medications let the forces that give a man an erection rule over those that would not.

One last explanation is needed before a comparison can be made. The difference between Viagra and Sildenafil must be understood.

Sildenafil is the active component in Viagra, but it is also in another drug called Revatio; so, sildenafil is both Viagra and something else, Revatio. The Sildenafil in Viagra is made in 3 doses (25 mg, 50 mg, and 100 mg) and is used for the treatment of Erectile Dysfunction (ED). The Sildenafil in Revatio comes only in a 20 mg dose and, in that dose, has been approved for the treatment of Pulmonary Hypertension.

Sildenafil is the generic name of the chemical in both those medications, but only Revatio has been approved for use as a generic medication. So, there is an inexpensive Sildenafil in the 20 mg tablet, but not an inexpensive generic of the 25, 50,100 mg tablets. Physicians have access to Sildenafil and can write it for any reason, not just to treat pulmonary hypertension, but when they use it to treat ED, it is considered “off label” use–even though it is exactly the same medication as in Viagra. This means that, while sildenafil is in pharmacies, only the generic 20 mg tablet is available for doctors and patients to use as an “off label” generic medication for the treatment of ED.

Soon, a generic form of Viagra will be released and, in practical terms, that means that sildenafil will be available not just as 20 mg tablets, but in 25 mg, 50 mg, and 100 mg tablets as a generic and, when written in those doses, will not be considered “off label” use. However, in those dosages the cost will be far greater than the 20 mg sildenafil presently available at pharmacies.

What does this mean for patients?

To review, Viagra, which is Sildenafil, has been approved “for the treatment of erectile dysfunction (ED), including ED patients with diabetes mellitus or following radical prostatectomy.” (PDR) Viagra is available in doses of 25 mg, 50 mg, and 100 mg. However, generic Sildenafil comes only in one size, 20 mg. The FDA approved Sildenafil in the low 20 mg dose for pulmonary hypertension, but since it is the same medication as in Viagra, and only a fraction of the cost, many patients work with their healthcare providers to use sildenafil “off-label” for erectile dysfunction (ED). Many find the cost of the brand sildenafil (Viagra) so high they cannot start the medication nor continue its use.

Most physicians who prescribe Viagra (Sildenafil) start patients on the 50 mg dose and either raise or lower the dose as warranted. One of the benefits of using sildenafil in the 20 mg dose is that you and your healthcare provider can raise or lower the dose more carefully.

A physician might write a prescription for a patient to take 2 of the 20 mg tablets of sildenafil (a 40 mg dose) one hour before sexual activity. Based on effectiveness and tolerance, the physician and patient may find it is appropriate to increase the dose to 60 mg (3 tablets), 80 mg (4 tablets), or the maximum 100 mg (5 tablets). On the other hand, a patient may find that a 20 mg dose (1 tablet) gives the effect he wants. At that dose it may even avoid an annoying side effect. Such fine shifts are not possible with brand sildenafil (Viagra). A physician can only jump from 50 mg to 100 mg if an increase is needed, or drop from 50 mg to 25 mg if a decrease is warranted. These are big jumps in dosages by comparison.

One of the other appealing aspects of the 20 mg tablet (besides the lower cost), is that patients can often adjust the dose with guidance from their healthcare provider based on factors not usually considered. They may find that a 20 mg dose is fine most of the time but that, on occasion, a 40 mg dose gives the man a bit more of what he wants (or a partner wants).

It could be that anxiety becomes an issue with a new relationship or stress at work proves to be more of a distraction than in the past. These issues can interfere with “erotic focus” or “awareness of sensory experience.”

Basically, it can take someone out of “the moment” making maintaining an erection a bit more of a challenge. Anything that reduces anxiety is helpful. Moreover, the ability to achieve a robust erection initially supports a positive feedback mechanism that allows a man to focus on his, and his partner’s, experience and not worry about the process.

The ability to use small incremental shifts in dosages allows for continued sexual activity while underlying issues are approached without being clouded by concerns about losing sexual intimacy.

A very brief comparison of these drugs can be made by examining how they can be used (‘as needed’ for all four, plus daily for Cialis), the time it takes for them to work, the length of time they work, the restrictions on how they can be taken, the contraindications to their use, and their side effects.

Though similar, ED medications have different effects and side effects. Sildenafil, Viagra, and Levitra (Vardenafil) have relatively rapid onsets of action compared to Cialis (Tadalafil).

Sildenafil, Viagra, and Levitra can be effective in as little as 1 hour, while Cialis might not take effect for 2 hours, though for some patients these medicines can work more rapidly. Viagra, Sildenafil, and Levitra will be out of the body in about 6 to 8 hours, while Cialis can work for 24 to 36 hours.

Levitra works about as quickly as Viagra and Sildenafil, and lasts about as long. However, it can be taken with food (as long as it is not excessively fatty), which is an excellent option with obvious real world usefulness. The effect of Sildenafil, Viagra, or Levitra may not be needed beyond 6 or 8 hours, and any side effects they cause will fade rapidly as a medication leaves the bloodstream.

The differences people experience in terms of the effects or side effects can make one drug preferred over the others, depending on a person’s circumstance. Sometimes, a peculiar side effect might prevent a man from taking Viagra or Sildenafil but not Levitra. Another person might not be able to take Levitra (Vardenafil) because they are on a medication that might lead to a cardiac arrhythmia.

How might choices be made? Consider two men.

One man might know sex will occur during the course of a weekend but cannot say when. A drug with a prolonged period of activity is far more important than how long it takes for it to start working. For him, tadalafil (Cialis). Also, Cialis can be taken in a low daily dose and for a solid subset of patients, this is preferred because the issue of timing disappears.

Compare this to a man who is able to predict when sexual activity will occur. A drug that works rapidly and leaves his system quickly thereafter would be perfect, as with Sildenafil or Viagra. If dining is part of the evening’s plan, Levitra may be a more practical choice, as it is unaffected by food and it too will be out of his system by morning. One restriction on the meal exists, however. It is not necessary to take Levitra on an empty stomach but a very fatty meal should be avoided. Fat interferes with its absorption where fat is more than 55% of the calories in a meal.

You may think Levitra (vardenafil) has a clear advantage over Viagra and Sildenafil for someone wanting to take a short acting tablet, but there is another important consideration. Levitra (Vardenafil) can cause an abnormality seen on EKG called QT prolongation, or make long QT syndrome more pronounced. If that occurs, serious irregular heartbeats can follow.

The list of medications that can cause QT prolongation is quite large.

One issue is rarely the sole factor when choosing a medication. It is the interplay between a man’s social circumstances and that of their partner, his need for a rapid onset of activity versus a long duration of action, the individual side effects, a person’s prior medical history, the other medications taken, and the very personal definition of what it means to achieve an erection satisfactory for sexual activity.

Viagra, Sildenafil, and Levitra leave the body in about 6 to 8 hours. That means that while they are very effective–approximately 75% of patients will achieve a satisfactory erection–they will work reliably only for 6-8 hours. Nevertheless, the effect of a medication may not be needed beyond 6 or 8 hours, and any side effects will fade rapidly.

Someone who experiences nasal congestion or flushing with Viagra, Sildenafil or Levitra (vardenafil) may find it an advantage to take the shorter acting medications, as opposed to Cialis. It might be worth a bit of nasal congestion during the time when sex will occur but there would be no reason to endure a stuffy nose 30 hours after sexual intimacy had concluded.

One other point about the Levitra versus Viagra and Sildenafil comparison. Levitra has one solid advantage over Sildenafil or Viagra, both of which can cause men to see a bluish tint. That is because Viagra and sildenafil not only affect phosphodiesterase 5 but also phosphodiesterase 6, which has a role in regulating the retina. Levitra has very little impact on phosphodiesterase 6 and significantly decreases the possibility of that side effect.

Again, it is never as simple as considering just one factor. There is a good deal of trial and error in finding the right medicine, the most effective dose, and the plan that results in the fewest side effects. Sometimes, a side effect is worth the benefit, sometimes not.

On occasion, a man will be on other medications that make a dose adjustment necessary. Even a simple antibiotic like erythromycin can alter how the body handles these ED medications. Grapefruit juice can do so, as well. Some medications lower blood pressure and each of these medications, Viagra, Sildenafil, Levitra, or Cialis, can add to that blood pressure lowering effect and be quite dangerous. Nitrates, nitrites, and nitroglycerin can all be dangerous when combined with medications that treat erectile dysfunction.

The key is to get educated and share all your information with each of your healthcare providers. Only by doing so can a safe, effective, and personalized treatment plan be crafted with your goals and your safety preserved.

There have been some studies comparing Viagra head to head with Cialis to see which is preferred by men and which is preferred by their partners. The study results are summarized below.

Cialis vs Viagra

Which one do men prefer?

In a European study [Eur Urol 2004;45:499-509], men were given either 20 mg of Cialis or 50 mg of Viagra for 12 weeks with opportunities to choose meds (or raise dosages) after the initial study period. “In the doses utilized in this study, 73% of patients preferred tadalafil with tadalafil dosing instructions for the treatment of their erectile dysfunction over sildenafil with sildenafil dosing instructions.” It should be noted the maximum dose of Cialis was compared not to 100 mg dose of Viagra (the maximum) but the 50 mg dose. Nevertheless, in most studies, about three quarters of patients prefer Cialis and one quarter prefer Viagra.

Which do the female partners of heterosexual males prefer?

In a study of 100 heterosexual couples in stable relationships (J Sex Med 2008;5:1198–1207), the men were placed on a 12 week course of either Cialis or Viagra. Then, the men used the alternate for another 12 weeks. The female partners were asked which drug they preferred: “A total of 79.2% of the women preferred their partners’ use of tadalafil, while 15.6% preferred sildenafil.”

The reasons for their preferences were sought by interview. They concluded that “While the women’s reasons for preferring tadalafil emphasized relaxed, satisfying, longer-lasting sexual experiences, those preferring sildenafil focused on satisfaction and drug effectiveness for their partner.”