 |
QUESTIONS AND ANSWERS CONCERNING THE DEPARTMENT OF HEALTH AND HUMAN SERVICES (DHHS) INTERIM RECOMMENDATIONS FOR PATIENTS WHO HAVE TAKEN EITHER FENFLURAMINE OR DEXFENFLURAMINE
(1) Why has the Department of Health and Human Services (DHHS) decided now to publish these recommendations?
With the withdrawal of fenfluramine and dexfenfluramine from the US market, many people have asked what they should do if they have taken these drugs. In order to try to provide guidance, based on the best information known at present, the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), and the National Institutes of Health (NIH) (all components of DHHS) collaborated with experts within the medical community to develop the interim recommendations issued on November 14. We stress that these recommendations may change as we get more information on this type of heart valve disease. At present, we believe these recommendations represent the best advice we can give patients who have taken these drugs. As we learn more about this type of heart valve disease, we will continue to discuss these matters with the medical and patient communities to determine if revisions of these recommendations are warranted in the future.
(2) What exactly is DHHS recommending?
Basically, DHHS is recommending three things for people who have taken fenfluramine or dexfenfluramine for any period of time, either alone or in combination with other drug products:
(a) Everyone of these people should see a physician to have a complete medical history taken and physical examination performed with particular emphasis on the heart and lungs. This examination is to determine primarily if there are any signs or symptoms of possible heart or lung disease.
(b) If the physician finds that heart or lung disease may be present, then these patients should have an echocardiogram to determine if there is any evidence of significant disease of the heart valves.
(c) Even if there is no evidence of heart or lung disease by history or on the physical examination, in one special situation, these patients' physicians should nonetheless strongly consider having an echocardiogram performed on the patient to determine if there is any evidence of significant disease of the heart valves. That situation is IF the patient needs to undergo a medical or dental procedure before which the American Heart Association recommends giving patients with certain heart valvular disease an antibiotic to help prevent an infection of the heart called bacterial endocarditis. The reason for the echocardiogram in this situation is to determine if a person without symptoms nonetheless has disease of the heart valves. If they do have heart valvular disease that needs antibiotic coverage, they need the antibiotic before undergoing a medical or dental procedure that could possibly lead to a heart infection.
(3) Are these DHHS recommendations different from the earlier recommendations of the American Heart Association (AHA) and the American College of Cardiology (ACC)?
In the following ways the three recommendations are similar. All three sets of recommendations urge that all persons exposed to these drugs get a thorough medical history and physician examination with special attention to the heart and lungs. In addition, all three recommend that those with a new murmur or heart disease symptoms, such as shortness of breath or swelling in the legs, receive an echocardiogram examination. The American Heart Association recommendations and these DHHS recommendations suggest that patients found to have certain types of leaky heart valves on echocardiogram receive antibiotic coverage before certain medical or dental procedures.
Developed in consultation with the American Heart Association, the American College of Cardiology, and the American Dental Association, these DHHS interim recommendations build on the earlier AHA and ACC recommendations and incorporate new information from the five investigators who reported their results in patients who had taken these drugs and were without symptoms indicated that only 17% of patients with cardiac valve problems diagnosed by echocardiography had a heart murmur that was heard on physician examination. As noted by the American College of Cardiology, obesity may make a heart murmur difficult for a doctor to hear. Thus, these DHHS interim recommendations suggest that, regardless of whether signs or symptoms are present, persons who have taken these drugs and are planning certain medical or dental procedures that cause bleeding should also have an echocardiographic evaluation before the procedure. This is important because persons with significant valvular disease need to receive antibiotic coverage to help protect them from developing bacterial endocarditis.
(4) What is an echocardiogram and does it hurt to have it performed?
An echocardiogram is an ultrasound examination of the heart. This is basically the same kind of procedure as the ultrasound examination performed to check the growth of the fetus in a pregnant woman. The echocardiogram machine uses ultrasound waves and a computer to help make a movie of a patient's heart and heart valve movements during the routine beating of the heart. This is usually done by placing a small instrument (transducer) on the chest wall along with some gel to help make the proper ultrasound connection. There is no pain associated with routine echocardiograms performed in this manner.
(5) What is bacterial endocarditis?
Endocarditis is an infection of the tissues that line the heart chambers and cover the heart valves. Endocarditis can be caused by bacteria (certain types of germs) getting into the blood stream and infecting the heart lining and valve covering as the bacteria-laden blood is circulated through the heart. The body's own defense systems do not work as well in the heart as they do in other parts of the body. As this type of endocarditis is caused by bacteria, it is called bacterial endocarditis.
(6) What is the relationship between leaky heart valves and bacterial endocarditis?
When the heart valves are not normal, they become more likely to develop this infection. Why this occurs is not fully known; however, years of experience have demonstrated that people with certain heart valve abnormalities are more likely to get endocarditis than those without valvular abnormalities if their blood contains enough of the bacteria that can cause this infection.
(7) Why can certain medical and dental procedures lead to bacterial endocarditis?
Different kinds of bacteria normally are found in all people's mouths, rectal areas, and in the tube through which they urinate ("urethra"). Normally only a small number of these bacteria get through the tissue barriers in those areas and enter the blood stream, usually only for a short period of time. In these situations, the body's own defense system destroys the bacteria before they can do any harm to the body. However, when certain medical or dental procedures are performed in these areas, especially those associated with bleeding, the numbers of bacteria and the length of time that the bacteria are getting into the blood stream can increase. This is because of the expected injury to the tissues that normally form a barrier to the bacteria. These events increase the chance that the bacteria will have the opportunity to infect an abnormal heart valve. Antibiotics given just before these types of medical or dental procedures can help the body's own defense system destroy the bacteria that get into the blood stream during the procedure. But even with antibiotics, bacterial endocarditis cannot be prevented in all cases.
(8) If persons who have taken these drugs need to have a medical or dental procedure that can cause bleeding, what should they do?
All persons who have taken these drugs should see their physician and have a careful health history and physical examination with special attention to the heart and lungs. If a person who has taken these drugs is planning a non-emergency medical or dental procedure (including, in some cases, certain dental cleanings) in which bleeding is anticipated, it is important that the person contact his/her physician to determine if this is a procedure for which antibiotic coverage is recommended if the patient has a valvular disorder. It is important to remember that not all medical or dental procedures result in situations for which antibiotic coverage is recommended by the American Heart Association for patients with leaky heart valves. A person's physician can advise him/her on whether or not the procedure warrants antibiotic coverage.
If it is determined that antibiotics are recommended before the planned procedure, then persons who have been exposed to these drugs should undergo an echocardiogram before the planned procedure. The echocardiogram is performed to determine whether they have valve leakage of a significant enough degree to require antibiotic coverage prior to the procedure.
(9) If I need to take antibiotics prior to certain medical or dental procedures, how is this done?
In these situations, your physician or dentist can prescribe the antibiotic to be taken. Usually the antibiotic is taken as a single dose, given by mouth, before you undergo the medical or dental procedure. People with leaky heart valves do not usually need to take antibiotics routinely at other times. If you need one of these medical or dental procedures right away and are not able to get an echocardiogram, your doctor or dentist can prescribe antibiotics even without knowing whether or not you have a leaky valve. After this, you should then be referred for the recommended cardiac evaluation and echocardiogram before any further non-emergency procedures. In all cases though, be sure to inform your doctor or dentist that you have taken medicines that may cause heart valve problems and about any allergies or bad reactions you have had in the past to any antibiotics. Recommendations for administering antibiotics to prevent endocarditis are found in the 1997 American Heart Association recommendations on the prevention of bacterial endocarditis.
(10) If I need to have an echocardiogram, how much does it cost, and who will pay for it?
The costs of doing and interpreting echocardiograms varies considerably across the country. Some of the factors that can determine cost include: (a) whether the examination is performed in a hospital, private office, or clinic; (b) individual physician fee variations; (c) geographic location where the examination was performed; and (d) managed care reimbursement agreements. You should contact your physician or medical care payer (insurance, HMO, Medicare, Medicaid, etc.) to determine how such examinations will be covered in your individual case.
(11) What medical follow up should I have if I am found to have heart valve problems?
As this is a newly recognized concern, we don't know yet what happens over time to people with this kind of heart valve problem. Based on data known at present, many of those patients affected don't have any symptoms of heart disease at present and don't require any treatment other than careful follow-up by their doctor and pre-treatment with antibiotics before certain medical or dental procedures, as previously described in these "Q&As". The significance of mild heart valve leakage in patients without symptoms is currently unknown. Some patients with heart valve problems do develop signs or symptoms of heart disease, such as shortness of breath, swelling in the legs, chest pain, or heart palpitations (feeling like your heart is "skipping" beats or is having "irregular" beats). If this happens, the patient may need additional medical treatment. Some patients may need referral to a cardiologist (heart specialist). A number of researchers are trying to determine if the valve problems associated with these drugs diminish, worsen, or stay the same over time. Over the next year, we should have more information about what happens to people with these kinds of leaky valves once they have stopped taking these medications.
(12) Do these drugs actually cause heart valve disease, and, if so, how?
At this time, no-one knows exactly what the relationship is between these drugs and heart valvular disease. Much further research is necessary before this question can be answered.
(13) Some media reports have suggested that other physicians have found much lower rates of valve disease in persons without heart or lung symptoms who were exposed to "fen-phen" than reported by FDA. What could be the reasons for these differences?
The data initially reported to FDA by five investigators were noted to be preliminary, but were striking in the consistently high rates of valve disease in patients without symptoms of heart disease examined at the five centers. Although the lay press has reported that some other physicians claim they have had lower rates of valve disease in their exposed patients, the data from these other physicians have not been sent to the FDA for review. It is important to remember that even if these physicians report lower rates, many of their reported rates are still higher than would be expected in the general population. And at present that's really the important point. Nonetheless, there could be several reasons that these reported rates are different: (a) the length of time the patients took the drugs, (b) the amount of drug the patients took, (c) other medications the patients might have been taking, (d) variations in the way the echocardiograms were interpreted by the readers, or (e) the length of time that had elapsed between the discontinuation of the drug and the time of the echocardiogram. There is still a great deal to be learned about this disease.
One way of more definitely exploring these questions would be to perform a study in a group of patients that includes both people who have taken these medications and people who have not taken them but who are otherwise similar in other characteristics (a "control" group). This would allow a more precise evaluation of differences between the groups.
Such a study was performed by Dr. Mehmood Khan in Minneapolis following the July announcement about the drug-associated valve disease. Dr. Khan reported his preliminary data this week from this NIH- and CDC-funded study. His data demonstrated that approximately 25% of the 226 patients in his study who had taken the drugs had significant leakage (regurgitation of mild or greater severity) around their aortic valve compared with only 1% of the 81 control patients in the study who had not taken the drugs had significant aortic valve leakage. These data are much stronger data than the survey type data previously reported by FDA or other physicians quoted in the press. These data continue to undergird the initial concerns raised about a possible connection between these drugs and the development of clinically significant cardiac valve disease.
(14) With the removal of these products from the market, what should overweight persons do if they want to improve their health?
A person who is less than 20% overweight should begin a life-long program of moderate physical exercise, such as brisk walking for 30 to 45 minutes, on most days of the week. Regular moderate physical activity is likely to improve weight control and will also strengthen the heart. Overweight persons should also begin to make moderate and life-long changes in their food choices and eating practices, including reducing the total amount of calories they eat and ensuring that their diet is low in saturated fat and rich in fruits and vegetables.
Persons who have a significant weight problem are advised to consult their physician to develop a strategy that is individualized for them. There are a number of options available that a physician can discuss with the patient.
(15) What future studies are now being planned by the federal government regarding diet drugs and valvular heart disease?
The NIH and CDC are jointly supporting an echocardiographic study of persons who took these diet drugs along with a group of persons who did not take the drugs who are matched as to age, gender, body weight, and weight loss. In addition, there are plans to extend the follow-up of persons with cardiac valve problems to determine if these problems improve, worsen, or stay the same. It is likely that the study will last for another 6 to 12 months.
(16) Are there further sources of information on this matter?
Further information on general issues regarding: the use of these drugs, cardiac valve disease, the treatment of obesity, studies being conducted about these conditions, endocarditis, and echocardiograms can be found on the websites of various organizations. You can easily get to the CDC and NIH websites, for example, by using the buttons in this website that provide immediate links to these and other web sites.
Date created: November 13, 1997; last update: July 7, 2005 |
|
