Impotence (ED) (cont.)

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What medications are used to treat erectile dysfunction?

Medications for erectile dysfunction include

  • testosterone,
  • oral phosphodiesterase type 5 (PDE5) inhibitors (sildenafil [Viagra], vardenafil [Levitra], tadalafil [Cialis]), avanafil (Stendra).
  • intracavernosal injections (trimix, Caverject, Edex),
  • intraurethral suppositories (MUSE).

Oral phosphodiesterase type 5 (PDE5) inhibitors

The common PDE5 drugs approved in the United States are sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis), or avanafil (Stendra). Actual head-to-head trials between these drugs have not been done to date to see which is the superior drug. Details on each of these medications for erectile dysfunction are outlined below.

Sildenafil (Viagra)

What is sildenafil (Viagra)?

Sildenafil (Viagra) was the first oral phosphodiesterase type 5 (PDE5) inhibitor approved by the FDA in the United States for the treatment of erectile dysfunction (it is not approved for women). Sildenafil inhibits PDE5, which is an enzyme that destroys cGMP. By inhibiting the destruction of cGMP by PDE5, sildenafil allows cGMP to accumulate. The cGMP in turn prolongs relaxation of the smooth muscle of the corpora cavernosa. Relaxation of the corpora cavernosa smooth muscle allows blood to flow into the penis resulting in increased engorgement of the penis. In short, sildenafil increases blood flow into the penis and decreases blood flow out of the penis.

How effective is sildenafil (Viagra)?

Sildenafil is used for the treatment of erectile dysfunction of either physical or psychological cause. It has been found to be effective in treating erectile dysfunction in men with coronary artery disease, diabetes mellitus, hypertension, depression, coronary artery bypass surgery, and men who are taking antidepressants and several classes of anti-hypertensives.

In randomized controlled trials, an estimated 60% of men with diabetes, and 80% of men without diabetes experienced improved erections with sildenafil.

How should sildenafil (Viagra) be administered?

Sildenafil is available as oral tablets at doses of 25, 50, and 100 mg. It should be taken approximately one hour before sexual activity. In some men, the onset of action of the drug may be as early as 11-20 minutes. Sildenafil should be taken on an empty stomach for best results since absorption and effectiveness of sildenafil can be diminished if it is taken shortly after a meal, particularly a meal that is high in fat.

What is the dose of sildenafil (Viagra)?

In prescribing sildenafil, a doctor considers the age, general health status, and other medication(s) the patient is taking. The usual starting dose for most men is 50 mg, however, the doctor may increase or decrease the dose depending on side effects and effectiveness. The maximum recommended dose is 100 mg every 24 hours, however, many men will need 100 mg of sildenafil for optimal effectiveness, and some doctors are recommending 100 mg as the starting dose.

Metabolism (breakdown) of sildenafil is slowed by aging, liver and kidney dysfunction, and concurrent use of certain medications (such as erythromycin - an antibiotic, and protease inhibitors, for HIV). Slowed breakdown allows sildenafil to accumulate in the body and potentially may increase the risk of side effects. Therefore in men over 65, in men with substantial kidney and liver disease, and in men who also are taking protease inhibitors, the doctor will initiate sildenafil at a lower dose (25 mg) to avoid accumulation of sildenafil in the body. A protease inhibitor ritonavir (Norvir) is especially potent in increasing the accumulation of sildenafil, thus men who are taking Norvir should not take sildenafil doses higher than 25 mg and at a frequency of no greater than once in 48 hours.

What are the side effects of sildenafil (Viagra)?

Sildenafil has been found to be well tolerated without important side effects. The reported side effects are usually mild and include headache, flushing, nasal congestion, nausea, dyspepsia, (stomach discomfort), diarrhea, and abnormal vision (seeing a bluish hue or brightness).

Sildenafil can cause hypotension (abnormally low blood pressure that can lead to fainting and even shock) when given to patients who are taking nitrates (for heart disease). Therefore, patients taking nitrates daily should not take sildenafil. Nitrates are used most commonly to relieve angina (chest pain due to insufficient blood supply to the heart muscle because of narrowing of the coronary arteries); these include nitroglycerine tablets, patches, ointments, sprays, and pastes, as well as isosorbide dinitrate, and isosorbide mononitrate. Other nitrates such as amyl nitrate and butyl nitrate also are found in some recreational drugs called "poppers."

Sildenafil should be used cautiously in men on alpha blockers such as doxazosin (Cardura), terazosin (Hytrin), and tamsulosin (Flomax). There have been occasional reports of low blood pressure in men who have taken the two classes of drugs simultaneously and therefore it is recommended that there be at least a span of four to six hours between the ingestion of sildenafil and alpha blockers.

There have been rare reports of priapism (prolonged and painful erections lasting more than six hours) with the use of PDE5 inhibitors such as sildenafil, vardenafil, and tadalafil, especially when sildenafil is used in combination with injection of medications into the corpora cavernosa or intraurethral suppositories. Patients with blood cell diseases such as sickle cell anemia, leukemia, and multiple myeloma have higher than normal risks of developing priapism. Untreated priapism can cause injury to the penis and lead to permanent impotence. Therefore, sildenafil should not be used in combination with intraurethral suppositories and corpora cavernosa injections. If there is prolonged erection (longer than four hours), immediate medical assistance should be obtained.

Is it safe for men with heart disease to use sildenafil (Viagra)?

Sildenafil has been found to be effective and safe in the treatment of erectile dysfunction in men with stable heart disease due to atherosclerosis of the coronary arteries, provided that they are not on any type of nitrates. The real concern is not as much the safety of sildenafil but the risk of sexual activity in triggering heart attacks or abnormal heart rhythms in patients with heart disease.

The risk of developing heart attacks or abnormal heart rhythms during sex is low in men with well-controlled hypertension, mild disease of the heart valves, well-controlled heart failure, mild and stable angina (with a favorable treadmill stress test), successful coronary stenting or bypass surgery, and a remote history of heart attack (more than eight weeks previously). Sildenafil can be used safely in men in these low-risk groups.

The risk of heart attack or abnormal heart rhythms during sex is higher in men with unstable angina (angina that occurs at rest or with minimal exertion), poorly controlled hypertension, moderate to severe heart failure, moderate to severe disease of the heart valves, recent heart attack (less than two weeks previously), potentially life-threatening disorders of heart rhythm such as recurrent ventricular tachycardia, and moderate to severe disease of the heart muscles. In these men, doctors usually stabilize or treat the heart conditions before prescribing sildenafil.

Before starting sildenafil for erectile dysfunction, a doctor may need to determine whether the heart can safely achieve the workload necessary for sexual activity. For example, in men with coronary artery heart disease, a doctor may perform a treadmill stress test to determine whether there is adequate blood supply to the heart muscle while exercising at levels comparable to sexual activity.

Medically Reviewed by a Doctor on 4/3/2014

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