Patient Information Leaflet Drug interaction with ED drug treatments This document is intended for information purposes only and should be used in conjunction with the advice and further details to be discussed by Mr. Ahmed at your consultation meeting. 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 Tables 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, also Poppers ), 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 Drug interaction with ED drug treatments (UH08) V1.2 Mar 2012 Page 1 of 6
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 on Page 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. Table 1. List of Drugs That May Cause Excessive Decreases in Blood Pressure When Taken with ED Drugs Isosorbide dinitrate Isosorbide mononitrate Nitroglycerin DILATRATE-SR, ISORDIL, SORBITRATE IMDUR, ISMO, MONOKET MINITRAN, NITRO-BID, NITRO-DUR, NITROSTAT, TRANSDERM- NITRO Alpha Blockers Nitrates Generic Name BRAND NAME(may be the brand name is different. Always check on the label for the generic name if not sure) Generic Name Doxazosin Prazosin BRAND NAME CARDURA MINIPRESS Terazosin HYTRIN Drug interaction with ED drug treatments (UH08) V1.2 Mar 2012 Page 2 of 6
Cyclosporine NEORAL, Tamsulosin FLOMAX SANDIMMUNE Alfuzosin UROXATRAL Darunavir PREZISTA Dasatinib SPRYCEL Table 2. Drugs That May Cause ED Drug Toxicity by Decreasing CYP3A4 Activity Delavirdine RESCRIPTOR Generic Name BRAND NAME Diltiazem CARDIZEM, CARDIZEM CD, DILACOR XR, TIAZAC Amprenavir AGENERASE Aprepitant EMEND Erythromycin EES, ERYTHROCIN Atazanavir REYATAZ Fluconazole DIFLUCAN Clarithromycin BIAXIN Fluvoxamine LUVOX Conivaptan VAPRISOL Drug interaction with ED drug treatments (UH08) V1.2 Mar 2012 Page 3 of 6
Fosamprenavir LEXIVA Posaconazole NOXAFIL Grapefruit Juice Quinupristin SYNERCID Imatinib GLEEVEC Ritonavir NORVIR Indinavir CRIXIVAN Saquinavir FORTOVASE, INVIRASE Itraconazole SPORANOX Telithromycin KETEK Ketoconazole NIZORAL Troleandomycin TAO Lapatinib TYKERB Verapamil CALAN, CALAN SR, COVERA-HS, Mifeprestone MIFEPREX ISOPTIN, ISOPTIN SR, VERELAN Nefazodone SERZONE Voriconazole VFEND Nelfinavir VIRACEPT Drug interaction with ED drug treatments (UH08) V1.2 Mar 2012 Page 4 of 6
Zafirlukast ACCOLATE Efavirenz SUSTIVA PLEASE DO NOT STOP ANY OF THESE Modafinil PROVIGIL DRUGS WITHOUT CONSULTING WITH YOUR DOCTOR. Nafcillin NALLPEN, UNIPEN Table 3. Drugs That May Inhibit the Effect of ED Drugs by Increasing CYP3A4 Activity Nevirapine VIRAMUNE Oxcarbazepine TRILEPTAL Generic Name BRAND NAME Phenobarbital LUMINAL, Aminoglutethimide CYTADREN SOLFOTON Bosentan TRACLEER Primidone MYSOLINE Carbamazepine CARBATROL, Phenytoin DILANTIN TEGRETOL Rifabutin MYCOBUTIN Dexamethasone DECADRON, HEXADROL, MYMETHASONE Drug interaction with ED drug treatments (UH08) V1.2 Mar 2012 Page 5 of 6
Rifampin RIFADIN, RIMACTANE Rifapentine PRIFTIN St. John s wort Disclaimer: This document is for information only and should not be used for the diagnosis or treatment of medical conditions. Urology and Healthcare has used all reasonable care in compiling the information but make no warranty as to its accuracy. Urology and Healthcare is the trading name of Urology and Healthcare Ltd. Drug interaction with ED drug treatments (UH08) V1.2 Mar 2012 Page 6 of 6