Eur J Haernatoll996: 57 (suppl): 5 Printed in LJK - all rights reserved

Copyright 0 Munksgaard 1996 EUROPEAN

JOURNAL OF HAEMATOLOGY ISSN 0902-4441

Preface This monograph derives from a meeting held in Saltsjobaden, Sweden, 12-14 October 1995, on the subject of drug-related blood dyscrasias. The conference was initiated and sponsored by Astra, the largest Swedish pharmaceuticals firm and one of the fastest growing pharmaceutical companies in the world.

The motivation for the conference came from an unfortunate and unpredictable experience the company had with a promising drug, Remoxipride, developed and first marketed by Astra in Europe in 1990. Clinical trials prior to marketing, as well as market experience with over 50,000 treated patients, had indicated that Remoxipride was a promising antipsychotic agent of great utility in patients with severe schizophrenia. Approximately 3 yr after Remoxipride became commercially available, however, 8 cases of aplastic anaemia, all occurring within a few months, were identified, and the drug was permanently withdrawn. Although a few patients in some countries continue to receive Remoxipride because of its apparent benefits, access is restricted to an individual, compassionate-use basis.

Aplastic anaemia is among the most feared adverse drug reactions. The clinical consequences of marrow failure, which can lead to fatalities, were of grave concern to both Astra and the treating physicians. In addition, the economic consequences of failure of a drug after marketing are always severe. Astra has analysed the Remoxipride experience in detail. All relevant data - preclinical and clinical -were reviewed closely, as was the character of the individual cases of aplastic anaemia associated with Remoxipride use. The literature was reviewed, appropriate experts were consulted, and frequent discussions held with regulatory agencies.

It soon became clear that there was a limited level of knowledge within the area of drug-related aplastic anaemia, which prompted this meeting. Astra decided to assemble a group of experts to discuss the general problem of idiosyncratic adverse haematological reactions to drugs, with special reference to aplastic anaemia. Purposely, scientists and physicians who had approached the problem of drug reactions from very different viewpoints were invited, including clinical haematologists, researchers in fundamental haematopoiesis, epidemiologists, pharmacologists and toxicologists. In the opinion of many of the participants, the conference was unique in its success at not only collecting, but also inspiring interaction among these scientists from highly diverse disciplines.

We hope this monograph will provide the reader with an overview of the current state-of-the-art knowledge in the area of drug-induced aplastic anaemia, a subject that has not been extensively reviewed recently. In addition, we hope that it will highlight issues that remain unresolved, but are of enormous importance to physicians involved in pharmaceutical development and to haematologists and scientists interested in blood dyscrasias.

Neil Young MD, Chairman

Marianne Keisu MD, Director of Product Safety,

Astra Arcus AB, Workshop Organizer