Watch out for Interactions Between Drugs for Erectile Dysfunction and Other Medications

Anyone with a television probably knows that three prescription medications currently are used to treat erectile dysfunction (ED): sildenafil (VIAGRA), tadalafil (CIALIS) and vardenafil (LEVITRA). These drugs, which belong to the class of drugs called phosphodiesterase-5 inhibitors (PDE5i), are widely used, especially in older men. And because older men are more likely to be concurrently taking other medications, they should be aware of the potential for dangerous interactions when ED drugs are mixed with other prescription drugs. This article deals only with these three approved prescription ED drugs, not the many untested ED products widely advertised on the Internet and elsewhere (see Table 1, 2, and 3).

How do ED drugs interact?
Sildenafil, tadalafil and vardenafil are drugs that cause the dilation of blood vessels (vasodilators) and this effect can be magnified when they are used with other medications with similar vasodilating effects. It is this vasodilating effect that increases blood flow to the penis causing an erection. Most ED drug interactions, however, result from the fact that these drugs are metabolized by the enzyme CYP3A4 in the intestine and liver. CYP3A4 is the most important enzyme for drug metabolism, and many medications can interact with ED drugs by decreasing or increasing CYP3A4 activity, causing ED drug levels to increase or decrease, respectively.

Interactions with vasodilators
People who take nitrates (drugs commonly used to dilate the blood vessels in the heart for patients with coronary artery disease, such as nitroglycerin), either on a regular schedule or as needed, should not use these ED drugs. A dangerous reduction in blood pressure may occur, potentially leading to a heart attack or stroke, and so these drugs should not be used in combination. ED drugs also can enhance the blood pressure-lowering effects of alpha blockers such as doxazosin (CARDURA), prazosin (MINIPRESS), terazosin (HYTRIN), tamsulosin (FLOMAX) and alfuzosin (UROXATRAL). These drugs are used to treat both high blood pressure and enlarge prostate glands. If you are on an alpha blocker, consult your physician before taking an ED drug; he or she may recommend dosage adjustments or other precautions.

Interactions with drugs that decrease CYP3A4 activity
Drugs that inhibit CYP3A4 can substantially increase plasma concentrations of ED drugs, potentially leading to toxicity. See Table 2 for a list of drugs that inhibit CYP3A4. If you are taking any of these drugs, check with your physician before taking an ED drug. Your physician may advise a dosage reduction of the ED drug, especially if you are taking a potent CYP3A4 inhibitor such as ketoconazole, itraconazole or ritonavir. Keep in mind that grapefruit juice is also a CYP3A4 inhibitor.

Interactions with drugs that increase CYP3A4 activity
Drugs that increase CYP3A4 activity (see Table 3) tend to reduce the effect of ED drugs. This is not dangerous, of course, but it may render the ED drug ineffective. If the increased CYP3A4 activity is marked — such as in patients taking the antibiotic rifampin, even the highest recommended dose of the ED drug may be ineffective. Again, if you are taking any of the medications in Table 3, talk to your physician before starting an ED drug so he or she will know that the effect of the ED drug may be compromised. (See Tables 1, 2 and 3).

What You Can Do
Many medications have the potential to interact with ED drugs, so it is important to make sure that the physician prescribing the ED drug is aware of all the other medications you are taking. If you start or stop other medications after receiving a prescription for an ED drug, check to make sure your ED drug effect will not increase or decrease as a result.