44 Drug Withdrawals From

the Market – Causes

and Consequences

Ronald D. Mann

44.1 Introduction

From the point of view of a pharmaceutical com-
pany, theworst way in which thingscan gowrong is
when the marketing authorization for a major pro-
duct is threatened with revocation or suspension
due to reports of serious or fatal adverse drug
reactions.
The losses involved in such a disaster can be so
sudden and so damaging that the threat polarizes
the Managing Director, the Medical Director, the
Marketing Manager and the rest of the Executives,
and sets them apart from one another. In most cases
it also bewilders them, for it is highly unlikely that
any of them will have previously faced such a
situation.
The relevant literature that might provide useful
examples and guidance is pretty sparse. Micturin
(terodiline hydrochloride) was withdrawn from
sale in 1991 after it was discovered that its use
was associated with serious cardiac arrhythmias,
most notably a rare and sometimes fatal form of
ventricular tachycardia known as torsades de
pointes. As we shall shortly see, other drugs have
been withdrawn for the same reason but the story of
terodiline was written up by the physician who was
Medical Director of the relevant company at the
time. This account (Wild, 2002) should be read by

anyonewho may become involved in a suddendrug

withdrawal due to toxicity, for it represents one of

the few such firsthand accounts in the literature. A

comparable account of the withdrawal of nomifen-

sine due to the unexpected occurrence of hemolytic

anemia has also been published (Stonier and

Edwards, 2002) and, again, this account records

the views and experience of the physician who was

Medical Director of the relevant company at the

time of the crisis and drug withdrawal.

It is a staggering fact that in the present state of

scientific knowledge we cannot prevent the loss,

after marketing, of licensed pharmaceuticals that

are found to produce unexpected grave toxicity.

This has been known for virtually 40 years and

yet the pharmaceutical industry has not seen fit to

organize itself collectively to protect companies

that suffer these unexpected and damaging drug

withdrawals. Drug regulatory bodies were set up in

Europe in response to the thalidomide disaster of

the very early 1960s. In the United Kingdom drug

regulation began with the Committee on Safety of

Drugs which was chaired by Sir Derrick Dunlop.

This Committee (the forerunner of the Committee

on Safety of Medicines) functioned from January

1, 1964 until it provided its last report for the

combined years of 1969 and 1970. The experience

of those six or seven years led the Committee, in its

Principles and Practice of Pharmaceutical Medicine, 2nd Edition Edited by L. D. Edwards, A. J. Fletcher, A. W. Fox and P. D. Stonier
#2007 John Wiley & Sons, Ltd ISBN: 978-0-470-09313-9