1996, fenfluramine was the 46th most frequently pre-
scribed drug in the United States. with sales of $176
million per year (roughly $209 million in 2006 dollars).
No long term studies were performed for these dtrugs,
and they were never approved for use in combination
therapy.
On July 8, 1997,The New England Journal of
Medicinepublished a report from the Mayo Clinic
describing 24 cases ofregurgitational valvular heart
diseasein women who had been treated with fenflur-
amine and phentermine. By September 30th, the FDA
had received a total of 144 reports of heart value
problems associated with fenfluramine, with or with-
out phentermine.
On November 19, 1997, the Centers for Commu-
nicable Disease Cintrol published a review of the cases
of heart valve damage associated with fenfluramine:... Of these 113 cases, 111 (98%) occurred among
women; the median age of case-patients was 44 years
(range: 22 68 years). Of these 113 cases, two (2%)
used fenfluramine alone; 16 (14%), dexfenfluramine
alone; 89 (79%), a combination of fenfluramine and
phentermine; and six (5%), a combination of all three
drugs. None of the cases used phentermine alone. The
median duration of drug use was 9 months (range: 1 39
months). Overall, 87 (77%) of the 113 cases were
symptomatic. A total of 27 (24%) case-patients
required cardiac valve-replacement surgery; of these,
three patients died after surgery....
The Food & Drug Admibnistration removed fen-
fluramine from the market. Approximately 18,000
people sued American Home Products, which had
marketed the drug, to recover damages, either from
the costs of actual injuries, or the cost of tests to
determine whether any damage had been done. In a
class action lawsuit, American Home Products agreed
to establish a trust fund with a reported value of $3.75
billion, with the money to be distributed among vic-
tims of the drug, depending on extent of injury. People
exposed to fenflursamine will be monitored for heart
valve problems for a period of 20 years.
Although fen-phen has been associeted with
another very important adverse effect,primary pulmo-
nary hypertension, the focus of all regulatory and legal
problems has been on the heart valve problems asso-
ciated with the drug.KEY TERMS
Anorectic—A drug which suppresses the appetite.
Dexfenfluramine—An anorectic drug formerly mar-
keted under the brand name Redux.
Etiology—The cause of a disease or medical
condition.
Fenluramine—An anorectic drug formerly marketed
under the brand name Pondimin.
Fluoxetine—An antidepressant drug, sold under the
brand name Prozac
Fluvoxamine—An antidepressant drug sold under
the brand name Luvox
Indicated—In medical terminology, reviewed and
approved by the United States Food & Drug Admin-
istration, or the comparable agency in other nations,
for a specific use.
Mono-amine oxidase inhibitor—A class of antide-
pressant drugs that act by blocking an ezyme that
destroys some of the hormones in the bRain. These
drugs have a large number of food and drug
interactions.
Mitral valve—a heart valve, also called thebicuspid
valvewhich allow blood to flow from the left auricleto the ventricle, but does not allow the blood to flow
backwards.
Paroxetine—An antidepressant drug sold under the
brand name Paxil
Phentermine—An anorectic drug sold under a large
number of brand names
Primary pulmonary hypertension—Abnormally
high blood pressure in the arteries of the lungs, with
no other heart disease causing this problem.
Racemic—A chemical term, relating to the way a com-
pound turns a bean of light. Racemic compounds are
composed of equal amounts of left turning and right
turning molecules. Molecules which turn a beam of
light to the right aredextrorotatorywhile those which
turn a beam to the left arelevorotatory.
Regurgitational valvular heart disease—A type of
damage to the heart valves which allows blood to
leak back through the valve.
Serotonine—A hormone that stimulates brain cells
and also causes blood vessels to constrict.
Sertraline—An antidepressant drug sold under the
brand name ZoloftFen-Phen