By SHANNA GHAZNAVI
The Food and Drug Administration withdrew fen-phen from the market without obtaining sufficiently convincing evidence of its adverse side effects first, said the developer of the FEN/PHEN protocol.
Pietr Hitzig, the doctor who coined the term and created the concept of fen-phen, said the FDA “blindly decided” to remove fen-phen from the market because of “very bad science,” in the Mayo clinic study of fen-phen’s side effects.
In a Mayo publication, Heidi Connolly, the cardiologist at Mayo responsible for the study, said, “We say that there appears to be an association between this combination of medications and valve disease, but we can’t prove it based on current information. Further study is required and planned.”
Connolly said a follow-up study is in process, in which more than 1,000 patients will be evaluated to “confirm or refute the association that we observed,” according to a Mayo clinic news release.
On Sept. 15, the FDA asked the manufacturers and marketers of fenfluramine, (the “fen” in fen-phen) and the closely related dexfenfluramine, to voluntarily withdraw the obesity treatments. The FDA did not request, however, that phentermine (the “phen” in fen-phen) be withdrawn.
According to an FDA news release, Michael A. Friedman, the lead deputy commissioner of the FDA, said the drugs were an “unacceptable risk” to patients. The FDA based its decision on the Mayo clinic study and more than 60 reports of heart valve disease following the release of that study in July.
Howard Christensen, a BYU statistics professor, said “no cause and effect claims are made” in the clinic’s report of its findings. He said, “they (the Mayo clinic) have done a responsible job of reporting their findings. The news media may be making a cause and effect case that isn’t justified.”
The Mayo clinic identified 24 women being treated with fen-phen who showed signs of “unusual valvular morphology and regurgitation,” according to the study.
Fenfluramine and dexfenfluramine alter serotonin metabolism in the brain and phentermine interferes with pulmonary clearance of serotonin.
“The mechanism of valve injury is uncertain, but may be related to an alteration in circulating serotonin,” according to the Mayo study.
According to the Mayo study, the effects of phentermine on the levels of serotonin in the body is a possible cause of pulmonary hypertension noted in eight of the 24 subjects in the study .
Hitzig said the clinic “took one case and made phentermine stand as a cause of pulmonary hypertension.” He said the Mayo study may have found an “epiphenomenon,” or a highly unlikely incident, then assumed it was the norm.
Hitzig also said the study was not valid since there was no control group and all the women came from the same geographic area.
According to the Mayo study, all the subjects were identified during routine procedures at the Mayo clinic in Rochester, N.Y., and no attempts were made to discover cases by any other means. There was no control group in the study.
Since the Mayo clinic’s study, other studies have been done, said Michael O’Hare, media spokesperson for Mayo.
In a news release Thursday, the U.S. Department of Health and Human Services said there are five surveys which show that 30 percent of patients who took fen-phen had valvular abnormalities.
The American College of Cardiology is also conducting the first controlled experiment in an attempt to establish an association between fen-phen and its side effects, O’Hare said.
The U.S. Department of Health and Human Services released preliminary recommendations for the medical management of those who have taken fen-phen
According to the news release, the following recommendations were based on knowledge of the association of fen-phen with the development of heart valvular disease: patients should see their doctors to determine if they have symptoms of heart or lung disease; if these symptoms do occur, patients should have an echocardiogram performed; always have an echocardiogram before any kind of surgical procedure.
Hitzig also said the Mayo clinic’s study can be further proved invalid since there is no confirmation of the valvular abnormalities in pathology reports.
According to the Mayo study, there was “an absence of pathological confirmation in the majority of cases.”
Though no conclusive statements can be made about an association between the use of fen-phen and valvular disease, left-sided regurgitant valvular disease, like that seen in fen-phen patients, is rare in a population of less than 50 years old, according to the Mayo study.
Christensen said that he could not determine the reference for the Mayo clinic’s claim that the occurrence of 24 cases is extremely rare and not explainable by chance.
