The questions and suggestions Dr. Alexander raises are relevant, timely and important. The Association and various agencies are currently wrestling with a revision of the original interim recommendations (MMWR Nov. 14, 1997) in the face of new data. The Association is working closely with these agencies in reviewing current published scientific literature, which Dr. Alexander cited in his letter, to support updating the recommendations.
Two major points in Dr. Alexander’s letter are most relevant to the current debate:
- – the potential allergic risk of empiric prophylactic antibiotic regimens prior to invasive dental procedures;
- – the additional expense incurred for unnecessary medical evaluation, including echocardiography.
The current literature, however, remains controversial and is inconclusive to address your concerns. The three publications you cited (Khan et al., Jick et al., and Weissman et al, N Engl Med., 339:11, 1998) each provides further support of the connection between fenphen and cardiac valvulopathy, but they differ with regard to the strength and clinical significance of this connection.
On the other hand, the publication by Burger et al and Schiller (Journal of the American College of Cardiology, 34:4, 1999) did conclude that the relationship between fenphen therapy and valvulopathy is weak. Valvular regurgitation, which is a measurement of valvulopathy in their studies, may only reflect age-related degenerative change, not degenerative change as a result of fenphen medication.
The duration of the study by Burger, however, is relatively short (97 days), and the dosages of the medications are relatively low (15 mg phentermine resin and one 20 mg tablet of dl-fenfluramine).
Based on the data available, Dr. Devereux in his editorial in the New England Journal of Medicine (339:11, 1998) concluded that evidence linking the use of fenfluramine or dexfenfluramine to heart-value regurgitation reaffirms the wisdom of the FDA’s decision to withdraw them from the market.
In addition, the incidence of clinically overt valvular disease after the use of fenphen for three or fewer months or for four or more months was low. Finally, though the absolute levels of risk differed, the study by Khan et al demonstrated that the use of high dose of fenfluramine (120 mg per day) may have contributed to the high rate of clinically significant aortic regurgitation, and thus confers a high risk of cardiac-valve abnormalities.
The Association appreciates the gravity of the issue involving the safety of dental patients and will continue to work closely with CDC and other regulatory agencies to keep members informed of any change in guidelines and recommendations relating to this issue in a timely manner.
This Editor’s Note was prepared with assistance from Chet Siew, Ph.D., director of Toxicology Research in the ADA’s Division of Science.
