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Cardiovascular Disease + Hormonal Therapy Prostatepedia_February 2016 Volume 1 No. 6 February 2016 Volume 1 No. 6 P1 In this issue.... In our February issue, we take a broader view of cardiovascular disease risk among men on a common form of hormonal therapy called GnRH agonists. (You may be more familiar with the brand name Lupron.) You’ll hear from Dr. Shellie Ellis and Mr. Sean O’Farrell, researchers who are looking at larger databases— the American SEER database and the Prostate Cancer Database, Sweden—to gain insight into both the relationship between cardiovascular disease risk and GnRh agonists and to discern patterns of GnRh agonist use in the United States. As O’Farrell points out, while these populationbased studies are interesting, we really do need a randomized clinical trial with many patients to truly evaluate risk. Of course, as most of you already know, cardiovascular disease is an enormous problem in the majority of American men before they’re even diagnosed with prostate cancer. Whether or not any given prostate cancer treatment adds to risk is almost beside the point, as Dr. Mark Moyad points out: ignoring cardiovascular disease in favor of prostate cancer is foolhardy at best. More prostate cancer patients die of cardiovascular disease than prostate cancer itself. A cardiovascular disease evaluation for every prostate cancer patient before he even starts hormonal therapy, as well as careful monitoring during treatment, has been a hallmark of my practice and ought to be standard care for all men. Charles E. Myers, Jr., MD Contents: Contributors: P 4 Mark Moyad, MD: Cardiovascular Disease + Hormonal Therapy Editor-in-Chief: Charles E. Myers, Jr., MD P 7 Sean O’Farrell, BsC, MR: Publisher Jessica Myers-Schecter Cardiovascular Disease Risk P10 Shellie Ellis, PhD, MA: GnRH Agonist Prescription Patterns Mission: We aim to provide useful current information about prostate cancer and its treatment. This information and the products and media advertised in this publication are advisory only. Individuals pictured are models and are used for illustrative purposes only. Please consult your physician for specific medical or therapeutic advice. Subscriptions: $55.00/12 Electronic Subscription $110.00/12 Print Subscription Sales Consultant Rod Schecter Business Consultant Rose Sgarlat Myers, PT, PhD Copyeditor Grier McCain Proofreader Robert M. Protz, MS Designer Verity Burgess Editorial + Billing Offices 274 Redwood Shores, #739 Redwood City, CA 94065 434-220-3774 [email protected] www.prostatepedia.net Administrative Offices PO Box 6696, Charlottesville, VA 22906 Prostatepedia is published in Charlottesville, Virginia by Rivanna Health Publications, Inc. Copyright February 2016. Rivanna Health Publications, Inc. All rights reserved. ISSN: 2381-4020 P2 February 2016 Volume 1 No. 6 February 2016 Volume 1 No. 6 P3 Mark Moyad, MD: Cardiovascular Disease + Hormonal Therapy Dr. Mark Moyad, the Jenkins/ Pokempner Director of Preventive & Complementary Medicine at the University of Michigan (Dept. of Urology), is a popular speaker at patient-centered prostate conferences in the United States and abroad. Moyad is dedicated to educating prostate cancer patients about the connections between diet, supplements, lifestyle, and health. Prostatepedia recently spoke with him about the importance of addressing cardiovascular disease in men on hormonal therapy. How much of a problem is cardiovascular disease in men newly diagnosed with prostate cancer? Dr. Mark Moyad: It’s arguably the number one cause of death in prostate cancer patients. It’s the quiet elephant in the room. Men have to be as concerned about cardiovascular disease as they are with their prostate cancer diagnosis. Do some prostate cancer treatments, like hormonal therapy, increase the risk of cardiac disease? Dr. Moyad: Whenever people ask me that, I almost always say it doesn’t matter. Because we already know that cardiovascular disease going into P4 February 2016 Volume 1 No. 6 “If cardiovascular disease isn’t discussed, you shouldn’t even be treated for prostate cancer.” Androgen Deprivation Therapy (ADT) is the number one cause of death in men. So even if ADT doesn’t increase risk, I’m already going to treat that patient as if he were at high risk for a cardiovascular event. I’m still going treat this person as if he’s just as likely to die of a cardiac event. You have to think heart-healthy as much as ADT-healthy before the first injection. It doesn’t mean we’re downplaying the prostate cancer. It means that life is a game of probability, so in order to beat the odds you need to do everything possible to reduce your cardiac risk to zero. If you do that, it takes care of all the other business that you’re worried about. We also know that ADT has been around for 30 years now because “What¹s the point of being treated for prostate cancer if you’re going to die of a cardiac event five years later?” it’s helped so many people. If we had something better, ADT would be gone tomorrow, because it does come with a lot of side effects, especially weight gain. Your triglycerides can go way up; your glucose can go way up. You’re going to want to work out less. You’re not going to have any testosterone. In the Mark Moyad perfect world, you would never get an injection of Lupron until you have had a discussion about the fact that if you don’t aggressively take care of your heart health, your existing heart disease will get worse. It may not be the drug per se, but all the indirect effects, such as lack of energy, slowed metabolism, slight anemia, weight gain, increased diabetes risk, increased cardiac risk, and possibly increased blood pressure. We’re not saying the drug itself directly does that, but if you add up all the little things it does and the patient isn’t very motivated, it can be bad. I’ll add that this whole scare about ADT and cardiovascular disease is complex. To put this in perspective, most of the randomized trials don’t show that ADT makes cardiovascular disease worse. The randomized trials published a couple years ago in Journal of the American Medical Association showed no difference. The observational studies show that ADT does make cardiovascular disease worse. That is why we’re battling back and forth. That is why you see one paper that says it makes it worse and another paper that says it doesn’t make it worse. The reason why you’ll probably never come to an answer is because it’s so complex. The health of the patient going into treatment matters. Does he have five other diseases that the ADT exacerbated? Is he completely healthy? You think a man’s doctor should aggressively address any risk of cardiovascular disease before he starts on ADT? Dr. Moyad: I think so strongly that it should be a part of it that if cardiovascular disease isn’t discussed, you shouldn’t even be treated for prostate cancer. What’s the point of being treated for prostate cancer if you’re going to die of a cardiac event five years later? In all honesty, you might as well just enjoy life. The idea, though, is not to have your urologist or oncologist become your cardiologist. The idea is for you to go back to your primary care doctor or cardiologist and say, “I’m about to start on this androgen deprivation therapy. I need to know my cardiac risk as it stands right now so I have a baseline and then we need to talk about how we can monitor this the whole time I’m on ADT.” This is not difficult. You’re basically setting up a meeting with your primary care doctor or going back to your cardiologist and saying, “I have to go on ADT. We need to aggressively monitor for any changes.” Let’s talk about the details of careful cardiovascular monitoring. Dr. Moyad: Make sure you’re going to be measured for what I call the Big Four. The first is weight: BMI and waist circumference. The second number is lipids: your LDL and HDL cholesterol and triglycerides. Blood sugar, hemoglobin A1c is number three. Blood pressure is number four. These are the only four numbers I really want people to be obsessed with. And they can work with their primary care physicians to monitor these. The mantra is: You need to know how these four numbers change during ADT as well as you know how your PSA is doing. What about diet and exercise? Dr. Moyad: As I said, most people going into ADT have some condition that increases risk, like high blood sugar. When your metabolism slows while you’re on ADT, your lipid profile gets worse, your weight gets worse, your blood pressure increases, and your triglycerides go up dramatically. Everything just gets worse with this weight gain problem. There have been actual studies of CT scans and other imaging scans of weight gain in people on ADT. Within very little time, they increase not only their subcutaneous fat, the fat right underneath the skins, but also the fat around their organs. You can get fat infiltration around liver and pancreas. You’re making all these organs work harder. Caloric control and exercise become important. And I’ll say that caloric control is just as important as exercise when you’re on ADT because what you eat right now is really going to matter in terms of weight gain. It really is. But yes, aerobic and resistance exercise are important. Some men work with a trainer; some do it by themselves. But just because you exercise, you can’t eat whatever you want or drink whatever you want. That’s a big problem, I think, in prostate cancer patients. As they get older, a lot of people turn to drinking as selfmedication. But alcohol is so concentrated in calories. What about medications— like metformin or statins? Dr. Moyad: If you need help beyond diet and lifestyle, you can start looking at the possibility of what I call in my books and medical articles, the easy to remember 3-letter acronym for health care professionals and patients known as S-A-M: Statin, Aspirin, and Metformin. The benefit that I see with these drugs is not necessarily their potential ability to slow the progression of the disease. We don’t necessarily know if they do that, but we do know they can reduce the potential toxicity of ADT due to any potential increase in cardiovascular disease. For example, if you are exercising and reducing calories, but are still gaining weight with a blood sugar level in the pre-diabetes range (100-125 mg/dl), then you may qualify for metformin to help with weight loss and blood sugar control. Taking a statin, aspirin, or metformin makes more sense February 2016 Volume 1 No. 6 P5 than worrying about which of the 100+ different supplements you should take during ADT. All three of these medications came from a natural source. They’re all dirt-cheap. They’re all generic. I am not saying you have to be on any of these medications, but many patients qualify for at least one going into ADT or during ADT. How do you think stress and depression factor into all this? Just hearing you’ve been diagnosed with prostate cancer can be incredibly stressful. Dr. Moyad: Acute stress or stress once in a while can be good. Acute stress can sometimes motivate you: “I’m not going to let this disease get me.” Sean O’Farrell, BsC, MR : Cardiovascular Disease Risk Sean O’Farrell, of King’s College London, is an author on a recent Journal of Clinical Oncology article on the risk of cardiovascular disease in men on ADT. Prostatepedia recently spoke with Chronic stress, which can happen with a diagnosis, can really make the whole situation worse. You become stoic. You’re stuck. You’re not motivated to do anything. You’re mentally and physically shackled. If men go back to their primary care physician for a cardiovascular evaluation before going on ADT, we can identify more of those suffering from depression or chronic stress, can we not? Dr. Moyad: It would catch all of it. A lot of times, patients will say, “I have a fog. I just feel like I’m in slow motion. I just don’t feel cognitively up to speed like I used to.” These are all significant things to tell a physician you trust. Knowing your objective numbers and discussing your subjective feelings (mood, stress, and anxiety) with the doctor you trust the most with your health is crucial and can make the difference between a tolerable or good experience with ADT and a miserable one. P6 February 2016 Volume 1 No. 6 him about cardiovascular disease risk in men on hormonal therapy. GnRH is a gonadotropin-releasing hormone receptor that is primarily located in the brain. You can target that receptor in two ways: through the use of GnRH antagonists like Firmagon, or through the use of GnRH agonists like Lupron. The antagonists like Firmagon are the newer form and have slightly fewer side effects. How is hormonal therapy used to treat prostate cancer? Mr. Sean O’Farrell: Your prostate cancer is very much dependent on testosterone and other hormones— androgens—for growth. One very effective treatment, particularly in the earlier stages of the disease, is to block testosterone. This is called androgen deprivation therapy (ADT). ADT comes in multiple forms. You can have surgical androgen-deprivation, also known as an orchiectomy, or you can be given drugs. In terms of the drugs, there are three arms. In one arm are antiandrogens, which only act on the tumor itself. In the other arm are GnRH agonists, such as Lupron, which globally inhibit androgens. The use of these GnRH agonists is commonly referred to as medical, or pharmacological, castration. “Being aware that this is actually a risk with GnRH agonists is where it starts.” We have focused on drugs like Lupron. GnRH agonists are particularly associated with side effects like sexual dysfunction. And, as we at King’s College London recently pointed out, together with others, these drugs are also associated with cardiovascular issues. Despite the side effects associated with these drugs, they are quite an effective treatment for prostate cancer. Your group published a series of papers analyzing the Prostate Cancer Database, Sweden. What is this database and why is it important? O’Farrell: Prostate Cancer Database, Sweden, or PCBaSe Sweden, is a comprehensive register of 96-98% of prostate cancer patients in Sweden. This database is possible in Sweden because every citizen has a tendigit personal identification number. PCBaSe links different databases through that ten-digit number. You can link up things like information about other diseases, their particular prostate cancer diagnosis, lifestyle factors, educational level, marital status, and so on. What made our study quite unique is that we looked at patient drug information in addition to other factors. We were able to track outpatient ADT prescriptions per person without linking to name. This was all done anonymously to maintain privacy. We tracked how many times an individual’s prescription was actually picked up, thereby getting a comprehensive picture of drug adherence. PCBaSe Sweden is a database that links together a lot of health care information about prostate cancer patients. It’s being extended to other diseases, as well. February 2016 Volume 1 No. 6 P7 Can you talk about your group’s study, as well as the follow-up published in March 2015? O’Farrell: Mieke Van Hemelrijck published the original study in the Journal of Clinical Oncology. We published this follow-up five years later, also in the Journal of Clinical Oncology. In the first publication, Van Hemelrijck and her colleagues looked at everyone with prostate cancer—whether you had ADT or not, whether you were undergoing watchful waiting or not, etc. They found that the highest risk for cardiovascular disease was among those on hormone therapy. “The best thing is to get advice from your physician. See a cardiovascular specialist, if you can.” By the time I started working on the project in 2013, we had a drug register. That drug register started in 2005; by the time we were able to look at the data, there was quite a comprehensive amount of information. We were able to split patients on ADT into those who had had orchiectomy, anti-androgens, or GnRH agonists. We also had a control cohort of patients. We had five age- and county area-matched controls per prostate cancer case as a comparison group. We were able to do a very comprehensive analysis of the different types of ADT, compare the types to their respective controls, determine P8 February 2016 Volume 1 No. 6 where the risk of a cardiovascular incident was really high, and determine if there was any difference in risk between types of androgen deprivation therapy. We tried to distill which form of ADT might be more associated with an increased risk of other diseases, such as cardiovascular disease. What are the implications for patients? Which is pretty common, isn’t it? O’Farrell: Being aware that this is actually a risk with GnRH agonists is where it starts. The more counseling you can get and advice you get as early as possible, the better and more you can prevent future cardiovascular events. O’Farrell: In Sweden, it is. In our dataset, something like 24% of people underwent that switch. Twenty-four percent of those who started on antiandrogens eventually moved on. Did you find that dose and duration of different types of ADT increased risk more than others? You published a paper on thromboembolic disease, as well, correct? O’Farrell: We didn’t look at dosage too much, but we did look at duration. We found, to our own surprise, that the risk for any cardiovascular event was at its highest within the first year on ADT, regardless of which type the patient was on. Cardiovascular risk was highest for those who had anti-androgens, GnRH agonists, or orchiectomy. O’Farrell: We looked at venous thrombosis and embolisms—blood clots in your veins that can be fatal. Thrombosis is a side effect that has also been associated with ADT. It’s a much more rare disease than overall cardiovascular disease, but it’s certainly something that can happen, and when it does happen, it can be dangerous. We stratified our analysis by how many cardiovascular events a man had had before being diagnosed with prostate cancer or before being given ADT. We found that those who had two or more cardiovascular events before treatment were the ones at highest risk during treatment. The other groups remained quite flat. Those with a history of cardiovascular disease who then get ADT— regardless of type—had the highest risk of cardiovascular disease in the first year on therapy. That was the seminal finding. We looked at the different types of ADT—GnRH agonists and surgical castration. We found that the risk for a thromboembolic event was also higher for those on GnRH agonists and those who had had an orchiectomy. What do you think is behind the increased risk during the first six months? O’Farrell: There are a number of different potential reasons, but I would stress that studies like ours are very much hypothesisgenerating. We need lab studies and clinical trials to really understand this association. Thrombosis experts may say there are other things, particularly with prostate cancer, that may affect this. The prostate cancer itself is known to be associated with increased thromboembolic events. If your disease progresses quickly, that can lead to an increased risk for thromboembolic events. We tried to account for any indication that your prostate cancer may have moved a bit faster than one would hope. Interestingly, the risk remained high after they switched to GnRH agonists. It wasn’t like the cardiovascular disease story, where the risk peaked and then dropped back to baseline. In this case, the risk went up very early and it stayed high. The main message we would gather from that is that hormone should really only be given to patients in whom it is indicated. Active surveillance may be better for people with earlier-stage disease. What about people who have already followed the treatment pattern you describe and feel they may be at risk? What should they do? O’Farrell: The best thing is to get advice from your physician. See a cardiovascular specialist, if you can. A lot of patients may not know that this is potentially an issue, But I would caution that these are epidemiological studies. They’re retrospective. They’re on big datasets. They’re not randomized. We need a randomized clinical trial with a very high number of patients to really say if the risk is there. We found that the group at highest risk for thromboembolic disease was those who started on antiandrogens and then switched to GnRH agonists because their disease was progressing. February 2016 Volume 1 No. 6 P9 Shellie Ellis, PhD, MA: GnRH Agonist Prescription Patterns “As time goes on, you will have more and more information about the physicians you see.” users in general and they remained low users. Shellie Ellis is an Assistant Professor at the University of Kansas. Her research focuses on physician decision-making and how health care policies and reimbursement influence treatment decisions. Prostatepedia recently spoke with her about her study on GnRH prescription patterns from 2000-2009. Talk to us about the reimbursement cuts associated with the Medicare Modernization Act (MMA). Shellie Ellis: Most people are familiar with the Medicare Modernization Act because it gave prescription benefits to Medicare beneficiaries, but it was actually a very wide-ranging piece of legislation. It reformed the logistics of how Medicare payments were delivered. At the same time, the MMA issued reimbursement cuts that affected some of the care that prostate cancer patients received. Within one portion of Medicare— Medicare Part B—physicians are directly reimbursed for drugs they administer to patients in the office. Some policymakers thought that many of these drugs were reimbursed at rates that exceeded the cost of administering and buying the drugs. There were a whole host of these drugs in Medicare Part B. P10 February 2016 Volume 1 No. 6 GnRH agonists like Lupron were part of that class of drugs for which reimbursements were cut as a result of the changes enacted in 2004. Then, a slightly more aggressive change happened in 2005 with a two-part reduction in reimbursement for physicians. This particular action was not necessarily taken with the intent to improve quality of care. Policymakers thought physicians were being reimbursed at rates far greater than physicians were spending on buying and keeping these drugs. It just so happened that GnRH agonists were one of the most widely prescribed drugs and so they rose to the top of the list of those considered highcost for the Medicare program. But, coincidentally, the drugs were being used to treat low-risk prostate cancer patients, which wasn’t recommended. Tell us about the paper you published last year. Ellis: We started by looking at the SEER-Medicare database. This database is a collection of administrative claims. Once physicians submit their Medicare claims to the Centers for Medicare & Medicaid Services (CMS), CMS makes those claims available to researchers. In particular, the National Cancer Institute (NCI) takes data from SEER registries, the state- and locality- based registries that collect all information about anyone diagnosed with cancer in their catchment area. SEER comprehensively searches hospital records and physician records to document cancer stage, grade, and any other kinds of clinical indicators about the cancer. They also collect data about patients themselves— where they live, and the communities in which they live. Then they de-identify that data and match it to the Medicare claims data. Others had looked at this database to see what happened when the reimbursement cuts went into effect. There appeared to be a 65% decrease in the use of GnRH agonists among men with localized prostate cancer. We noticed this large decrease in GnRH agonist use and were interested in understanding how physicians were responding to the reimbursement cut as well as the characteristics of physicians who did not respond to the reimbursement cut. We characterized GnRH agonist use from 2000 to 2009 and identified different groups of physicians. There were some physicians who really didn’t use GnRH agonists at all for their low-risk, localized prostate cancer patients; their use of the drug didn’t really change after the reimbursement cut. They were low We also identified a group of physicians who used the drug quite a bit, but when the reimbursement cut happened, they decreased their use of the drug dramatically. We also noticed a group of physicians who didn’t use the drug a lot, but when the reimbursement changes happened, they actually increased their use of the drug substantially, much higher than even the users who had used it quite a bit prior to the reimbursement cuts. These were doctors who, despite the reimbursement cuts, were still electing to use drugs that might not be appropriate for their patients. We wanted to know more about this phenomenon, specifically, the characteristics of the doctors using the drug inappropriately, as well as the patients that they saw. One thing that was really interesting was that the patients who were being prescribed the drug inappropriately were more vulnerable patients than you might typically see. They were more likely to be African American. They were more likely to be older. They were more likely to be in communities with low socioeconomic status and education. use of a drug in certain ways. They might suggest that when a physician is faced with a reimbursement cut, he or she might actually increase the number of times the drug is given to make up for lost revenue. You get less per administration, but you’re doing it more often to compensate. But few of the economic theories actually partner the clinical data with the theoretical data about the physicians’ behavior. practitioners funneling information and knowledge to them. They don’t have time to pursue educational opportunities because they’re the only doctor in the practice. They might just be behind on some of the data that was coming out at the time about the harms of GnRh agonists or the guidelines published in 2000 that suggested this particular treatment was not appropriate for low-risk patients. What we saw is that these patients were very different from the patients of the doctors who decreased their use. It is well established that men who are older are more likely to be prescribed these drugs. They may be exhibiting other symptoms or have other diseases to which the physicians are responding. Or perhaps they’re not candidates for surgery. If these patients are of lower socioeconomic status, perhaps they can’t afford surgery or have other barriers to care. The patients themselves may not want radiation therapy, but want some type of therapy to relieve symptoms or simply because they have anxiety about a prostate cancer diagnosis. It is possible these physicians were responding to things we can’t see in the SEER-Medicare data. You’ve only looked at patients diagnosed through 2007. Any plans to look at what has happened between 2009 and now? But even though these things might explain the uptick in drug use, they still aren’t appropriate for the patient, so we wanted to identify which physicians were more likely to overuse the drugs. We found physicians in solo practice and those without any affiliation with a medical school were more likely to do so. We think it’s really important to reach out to those particular physicians and make sure that they’re aware of the risks. Why do you think this phenomenon is more likely to happen among solo practitioners? Ellis: We looked at patients diagnosed through 2007, but we had data through 2009. And yes. I just applied for the updated SEER-Medicare dataset. What do you think patients should take away from this? Ellis: As time goes on, you will have more and more information about the physicians you see. Try to stay informed and work with your physician. If at all possible, understand what guidelines are available. What evidence do we have to support that this is the best treatment possible? Organizations like the National Comprehensive Cancer Network publish guidelines available to you, so you can identify what treatments are appropriate for your particular stage of disease. About 20% of urology care is delivered in solo practices. Most of our traditional efforts to reach physicians, such as medical school affiliations or professional societies, have improved quality of care. Those kinds of opportunities may not be reaching solo doctors. We need to figure out new strategies for reaching those particular physicians. What do you think is behind that? Ellis: Some economists might explain this behavior of physicians’ increasing Ellis: We can’t tell exactly from the data we have. It may be because they’re by themselves and don’t have other February 2016 Volume 1 No. 6 P11 XTANDI takes on advanced prostate cancer while you take on what matters to you. Who is XTANDI for? XTANDI is a prescription medicine used to treat men with prostate cancer that no longer responds to a medical or surgical treatment that lowers testosterone and that has spread to other parts of the body. FIND OUT HOW YOU CAN FIGHT BACK. Talk to your doctor and visit XTANDI.com/info Important Safety Information Who should not take XTANDI? XTANDI is not for use in women. Do not take XTANDI if you are pregnant or may become pregnant. XTANDI can harm your unborn baby. It is not known if XTANDI is safe and effective in children. Before you take XTANDI, tell your healthcare provider if you: • Have a history of seizures, brain injury, stroke or brain tumors. • Have any other medical conditions. • Have a partner who is pregnant or may become pregnant. Men who are sexually active2016 with a pregnant woman must use a condom 1 P12and February Volume No. 6 during for 3 months after treatment with XTANDI. If your sexual partner may become pregnant, a condom and another form of birth control must be used during and for 3 months after treatment. Talk with your healthcare provider if you have questions about birth control. See “Who should not take XTANDI?” • Take any other medicines, including prescription and over-the-counter medicines, vitamins, and herbal supplements. XTANDI may affect the way other medicines work, and other medicines may affect how XTANDI works. You should not start or stop any medicine before you talk with the healthcare provider that prescribed XTANDI. How should I take XTANDI? • XTANDI is four 40 mg capsules taken once daily. • Take XTANDI exactly as your healthcare provider tells you. • Take your prescribed dose of XTANDI one time a day, at the same time each day. • Your healthcare provider may change your dose if needed. • Do not change or stop taking your prescribed dose of XTANDI without talking with your healthcare provider first. • XTANDI can be taken with or without food. • Swallow XTANDI capsules whole. Do not chew, dissolve, or open the capsules. • If you miss a dose of XTANDI, take your prescribed dose as soon as you remember that day. If you miss your daily dose, take your prescribed dose at your regular time the next day. Do not take more than your prescribed dose of XTANDI in one day. • If you take too much XTANDI, call your healthcare provider or go to the nearest emergency room right away. You may have an increased risk of seizure if you take too much XTANDI. What are the possible side effects of XTANDI? XTANDI may cause serious side effects including: • Seizure. If you take XTANDI you may be at risk of having a seizure. You should avoid activities where a sudden loss of consciousness could cause serious harm to yourself or others. Tell your healthcare provider right away if you have loss of consciousness or seizure. Your healthcare provider will stop XTANDI if you have a seizure during treatment. • Posterior Reversible Encephalopathy Syndrome (PRES). If you take XTANDI you may be at risk of developing a condition involving the brain called PRES. Tell your healthcare provider right away if you have a seizure or quickly worsening symptoms such as headache, decreased alertness, confusion, reduced eyesight, blurred vision or other visual problems. Your healthcare provider will do a test to check for PRES. Your healthcare provider will stop XTANDI if you develop PRES. The most common side effects of XTANDI include weakness or feeling more tired than usual, back pain, decreased appetite, constipation, joint pain, diarrhea, hot flashes, upper respiratory tract infection, swelling in your hands, arms, legs, or feet, shortness of breath, muscle and bone pain, weight loss, headache, high blood pressure, dizziness, and a feeling that you or things around you are moving or spinning (vertigo). XTANDI may cause infections, falls and injuries from falls. Tell your healthcare provider if you have signs or symptoms of an infection or if you fall. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of XTANDI. For more information, ask your healthcare provider or pharmacist. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. Please see the Brief Summary on the following page and the Full Prescribing Information on XTANDI.com. QUESTIONS ABOUT XTANDI? Call 1-855-8XTANDI (1-855-898-2634) XTANDI, Astellas, and the flying star logo are trademarks of Astellas Inc. 1 Pharma February 2016 Volume No. 6 P13 © 2015 Astellas Pharma US, Inc. 076-1030-PM 8/15 PATIENT INFORMATION XTANDI® (ex TAN dee) (enzalutamide) capsules What is XTANDI? XTANDI is a prescription medicine used to treat men with prostate cancer that no longer responds to a medical or surgical treatment that lowers testosterone and that has spread to other parts of the body. It is not known if XTANDI is safe and effective in children. Who should not take XTANDI? XTANDI is not for use in women. Do not take XTANDI if you are pregnant or may become pregnant. XTANDI can harm your unborn baby. What should I tell my healthcare provider before taking XTANDI? Before you take XTANDI, tell your healthcare provider if you: • have a history of seizures, brain injury, stroke, or brain tumors • have any other medical conditions • have a partner who is pregnant or may become pregnant. Men who are sexually active with a pregnant woman must use a condom during and for 3 months after treatment with XTANDI. If your sexual partner may become pregnant, a condom and another form of effective birth control must be used during and for 3 months after treatment. Talk with your healthcare provider if you have questions about birth control. See “Who should not take XTANDI?” Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. XTANDI may affect the way other medicines work, and other medicines may affect how XTANDI works. You should not start or stop any medicine before you talk with the healthcare provider that prescribed XTANDI. Know the medicines you take. Keep a list of them with you to show your healthcare provider and pharmacist when you get a new medicine. How should I take XTANDI? • Take XTANDI exactly as your healthcare provider tells you. • Take your prescribed dose of XTANDI one time a day, at the same time each day. • Your healthcare provider may change your dose if needed. • Do not change or stop taking your prescribed dose of XTANDI without talking with your healthcare provider first. • XTANDI can be taken with or without food. • Swallow XTANDI capsules whole. Do not chew, dissolve, or open the capsules. • If you miss a dose of XTANDI, take your prescribed dose as soon as you remember that day. If you miss your daily dose, take your prescribed dose at your regular time the next day. Do not take more than your prescribed dose of XTANDI in one day. • If you take too much XTANDI, call your healthcare provider or go to the nearest emergency room right away. You may have an increased risk of seizure if you take too much XTANDI. What are the possible side effects of XTANDI? XTANDI may cause serious side effects including: • Seizure. If you take XTANDI you may be at risk of having a seizure. You should avoid activities where a sudden loss of consciousness could cause serious harm to yourself or P14 February 2016 Volume 1 No. others. Tell your healthcare provider right away if you have loss of consciousness or seizure. Your healthcare provider will stop XTANDI if you have a seizure during treatment. • Posterior Reversible Encephalopathy Syndrome (PRES). If you take XTANDI you may be at risk of developing a condition involving the brain called PRES. Tell your healthcare provider right away if you have a seizure or quickly worsening symptoms such as headache, decreased alertness, confusion, reduced eyesight, blurred vision or other visual problems. Your healthcare provider will do a test to check for PRES. Your healthcare provider will stop XTANDI if you develop PRES. The most common side effects of XTANDI include: • weakness or feeling more • swelling in your hands, tired than usual arms, legs, or feet • back pain • shortness of breath • decreased appetite • muscle and bone pain • constipation • weight loss • joint pain • headache • diarrhea • high blood pressure • hot flashes • dizziness • upper respiratory tract • a feeling that you or things infection around you are moving or spinning (vertigo) XTANDI may cause infections, falls and injuries from falls. Tell your healthcare provider if you have signs or symptoms of an infection or if you fall. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of XTANDI. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store XTANDI? • Store XTANDI between 68°F to 77°F (20°C to 25°C). • Keep XTANDI capsules dry and in a tightly closed container. Keep XTANDI and all medicines out of the reach of children. General information about XTANDI. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use XTANDI for a condition for which it was not prescribed. Do not give XTANDI to other people, even if they have the same symptoms that you have. It may harm them. This Patient Information leaflet summarizes the most important information about XTANDI. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about XTANDI that is written for health professionals. For more information go to www.Xtandi.com or call 1-800-727-7003. What are the ingredients in XTANDI? Active ingredient: enzalutamide Inactive ingredients: caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, black iron oxide Manufactured by: Catalent Pharma Solutions, LLC, St. Petersburg, FL 33716 Marketed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Medivation Inc., San Francisco, CA 94105 14L082-XTA-BRFS © 2015 Astellas Pharma US, Inc. XTANDI® is a registered trademark of Astellas Pharma Inc. 076-1121-PM This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: August 2015 Personalized Treatment Your prostate cancer is as individual as you are. For an Appointment With Dr. Myers at AIDP, Contact Tel. 434-964-0212 (For appointments, press option #1) Fax. 434-964-0216 www.prostateteam.com February 6 Individuals pictured are models and are used for illustrative purposes only. 2016 Volume 1 No. 6 P15 274 Redwood Shores, #739 Redwood City, CA 94065 434-220-3774 [email protected] www.prostatepedia.net