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Older men who have less frequent sex and who are happy with the responses using Viagra should certainly continue Viagra. Some patients who do not get optimal responses to Cialis may find that Viagra is more to their liking. In general, all three drugs work and the patients should talk to their doctors about finding the one that works best for them and their sexual lifestyle. (Main information created August, 2004, some content updated 2006)

ImageThree drugs now and others in various stages of clinical trials has not only further expanded the treatment options for ED, but in many ways has caused new confusion among physicians and patients. Add this to other medications and vacuum therapy and it’s easy to see why patients and potential patients have questions.

For all practical purposes, these oral drugs are a first line of medical treatment. In certain circumstances in which the males are healthy, young, and laboratory blood tests and such are normal one should look for the physical cause of their erectile dysfunction before instituting treatment since the disease process may be more serious than the symptoms, i.e., the ED itself.

In some cases, treatment of the primary disease may in fact resolve the sexual dysfunction. However, most men have other physical causes for ED as found in their health history and lab tests, making PDE-5 inhibitors a first line of choice. Selecting the appropriate drug is sometimes extremely difficult to do without proper information on each drug and a careful discussion about the sexual history of the patient and his partner.

Let us discuss the pros and cons of each of these three drugs and the sexual circumstances that may indicate the use of one drug over another.

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Viagra was the first and is probably the most famous of the three PDE-5 inhibitors used to treat erectile dysfunction. It had been researched for over a dozen years before becoming available to the American public. It works in about 70% of all men with all types of erectile dysfunction, although approximately 25% of them do not feel that the responses are optimal. When initially doing the studies on Viagra, the endpoint of efficacy was improvement in sexual function; however, all patients in the Viagra studies had ED, whereas studies for the other two drugs were based on patients who had success with Viagra.

Viagra’s major drawbacks include decreased absorption due to food intake. You should take the pill on an empty stomach as absorption takes approximately 30 minutes. The drug takes about one hour for maximum effect, but loses 50% of its maximal concentration every four hours. Sexual stimulation is necessary to achieve erection. Of the three drugs, the maximal concentration for Viagra appears to be the therapeutic concentration. Side effects include mild headaches, facial flushing, stomach upset and unusual ocular disturbances including a bright vision and a blue-green halo around the vision.

Levitra was the second oral PDE-5 inhibitor for erectile dysfunction to be FDA approved. In vitro, it is six to 10 more times more potent than Viagra, however, 15% of the drug is nonprotein-bound and bioactive. Studies on Levitra have excluded patients who did not have success with Viagra, therefore the efficacies are somewhat shifted toward the positive. In general, the thought is that Levitra is more potent and efficient than Viagra as demonstrated by the hard-to-treat groups of patients. Diabetics and post-radical-nerve-sparing-prostatectomy patients appear to have a higher incidence of success than for Viagra. In addition, the efficacy is based on sexual satisfaction or successful penetration rather than improvement, which were the endpoints for Viagra.

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Levitra reaches its peak concentration at 40 minutes, is only affected by a very high fat diet. Most patients can eat and take the drug without affecting its absorption and maximal concentration. The half-life of Levitra is five hours; however, the therapeutic levels appear not to be the maximal concentration and therefore multiple half-lives may occur with efficacy of the drug. In Europe, Levitra is considered a 24-hour drug whereas in the United States the package insert states, “No duration of action for Levitra” although the majority of physicians consider it to be a drug that has efficacy longer than Viagra.

Overall the slight chemical change noted in Levitra appears to give it more potency, efficacy, longer duration, and probably more rapid onset. Levitra has shown that 25% of patients had optimal responses within 16 minutes of the oral intake of the pill. In recent studies, Viagra has also shown longer duration of action than four hours even though the package insert shows four hours of duration. However, if duration is the goal, Cialis appears to be the winner.

Cialis has been approved for duration of 36 hours, yet, there are studies showing high efficacy out to 100 hours. It is not affected by any food whatsoever and in fact can be taken with pure fat. The typical McDonald’s double cheeseburger with French fries and malted milkshake would certainly inhibit the effect of Levitra, but a steak with potatoes, a glass of wine, salad, and dessert would probably not. Neither of these would affect the absorption of Cialis. Cialis is protein-bound that causes a serum peak concentration of two hours and a half-life anywhere between 16 and 22 hours depending on the age of the patient. The older the patient, the longer the half-life. Because of the long duration of action, the lack of absorption effects, and efficacy at least as good as Viagra, if not better. The paradigm of taking these PDE-5s may in fact change as people gain more and more experience with Cialis.

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Cardiac-wise Cialis has the shortest QTc interval and may in fact be the safest to use for cardiac patients although all three drugs are extremely safe. None of them have a QTc interval of greater of 10 milliseconds, which would have caused the drug to fail FDA clearance. The long half-life of approximately 20 hours is not unusual in today’s modern health. Most drugs given by general practitioners to their patients have half-lives even greater than 20 hours and there is no concern about side effect profiles. If side effects occur with Cialis, they are usually short duration, mild, and occur within the first 24 hours.

(This information was written in August 2004) Another concern about Cialis is the fact that it has the greatest affect on the PDE-11 enzyme system, which is found in many organs including the heart, muscle, and testicle. Concerns about fertility have been diminished with several studies of six-months duration/two sperm cycles in which there appears to be no quantitative or qualitative abnormalities in the semen analysis. Longer studies or experiences may be necessary to determine whether or not this drug does in fact have negative effects on fertility in men. In addition, muscle aches and pains particularly in the low back and gluteal area are more common with Cialis (7%) versus Levitra or Viagra (less than 1%). Younger, more muscular and more physically active men, particularly when confined or not physically active for a period of time, get this discomfort, which seems to be related to PDE-5 inhibitors in general and muscular vascular congestion. Physical activity makes the pain disappear and in addition when taking multiple Cialis tablets in time the discomfort disappears. One interesting study involved PDE-11 knockout rats in which the genetic material to make PDE-11 has been destroyed and the generations of rats that form have no PDE-11 activity. There was found to be no fertility, muscle pathology, or cardiac pathology in these rats indicating that PDE-11 inhibition even though unknown appears not to be detrimental.

Having discussed the basic information about Viagra (sildenafil), Levitra (vardenafil), and Cialis (tadalafil) let us look at the ideal circumstances for using these drugs.

Cialis with its long half-life and relatively long duration of action of 36 to 100 hours appears to be the easiest, most cost effective, spontaneous, and natural of the three drugs. Two or three pills per week may be all that is necessary for function without concern for time and spontaneity.

On the other hand, having the ability to maximize nocturnal erections by using two pills per week of Cialis is extremely advantageous since it maximizes nocturnal blood flow during the three to five erections that every male gets at night, oxygenates the penis, decreases the chances of fibrosis and scarring, and in the process prevents irreversible penile damage and irreversible untreatable erectile dysfunction. As we gain experience, it is possible that the treatment of choice will be to combine Cialis with one of the shorter-acting drugs. A booster of Levitra or Viagra prior to sexual activity after taking Cialis on Tuesday and Friday may be the ideal choice for many patients who do not get an optimal response to 20 mg of Cialis every 36 hours. Lastly, if sexual activity occurs more than twice per week Cialis becomes more cost effective and becomes the drug of choice.

For those patients who have hard-to-treat erectile dysfunction, Levitra may be the drug of choice because of its relatively high potency and effectiveness in these types of patients. Many think of Levitra as a more potent Viagra, however, Levitra has a much longer duration of action and in many men a 20 mg Levitra tablet will be effective with stimulation up to 20 or 24 hours. Levitra tends to work very rapidly with 25% of the patients getting an optimal response within 16 minutes of taking the drug. Certain individuals, such as single men who cannot plan their sexual activity until the last minute, may find Levitra to be their drug of choice.

Viagra has certainly maintained itself over time as the safest “gold standard” of PDE-5 inhibitors. We are really not able to compare Viagra to Levitra and Cialis because the studies on Viagra used improvement in sexual function rather than penetration or sexual satisfaction as their endpoint and therefore the efficacy statistics may be higher than they should be.

On the other hand, Levitra and Cialis used penetration and sexual satisfaction as their endpoint, but disqualified those patients who did not respond to Viagra; therefore their efficacy figures may in fact be higher than they should be. Both inequalities may actually cancel each other out and many feel from an efficacy point of view that the three drugs are fairly close in their ability to produce satisfactory and optimal erections for sexual activity.

Viagra has the longest safety record and profile of just about any drug approved by the FDA. However, Levitra and Cialis have equally safe profiles for a shorter period of time. The overall side effect profile percentages for all three drugs are approximately the same with the exception that there are no eye manifestations or flushing with Cialis and minimal eye manifestations with Levitra. However, there is some question as to whether or not Levitra and Cialis have a milder degree of side effects including headache, stomach upset, and nasal congestion. Cialis rarely causes nasal congestion.

Older men who have less frequent sex and who are happy with the responses using Viagra should certainly continue Viagra. Some patients who do not get optimal responses to Cialis may find that Viagra is more to their liking. In general, all three drugs work and the patients should talk to their doctors about finding the one that works best for them and their sexual lifestyle. (Main information created August, 2004)

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