Adverse drug reactions: prescribing's twilight zone

Prescribing means treading the fine line between efficacy and tolerability, whether it is aspirin’s association with gastrointestinal bleeding and Reye’s syndrome, warfarin’s notoriously narrow therapeutic window or a new medicine with a unique, poorly characterised mode of action. Unfortunately, however, prescribers often have an incomplete picture of adverse drug reactions (ADRs), even with well-established medicines. “We are plagued by having to make prescribing decisions, and choose drugs based on an incomplete picture of the benefit/harm profile,” remarks Yoon Loke, professor of medicine and pharmacology at the University of East Anglia. Most phase 3 studies, for instance, enrol a selected group of patients, typically with fewer co-morbidities, on fewer concomitant medications, and less ill than many of those managed in routine clinical practice. In addition, phase 3 studies often enrol inadequate numbers of patients to detect rare ADRs. In the UK, for example, the annual number of cases of Reye’s syndrome – a serious, often fatal swelling of the liver and brain – declined from 81 in 1983– 84 to five in 1996–97.1 The decline followed advice from the Committee on Safety of Medicines – the precursor of the Medicines and Healthcare products Regulatory Agency (MHRA) – to not prescribe aspirin to children. “The advice vir tually eliminated cases of Reye’s syndrome,” notes Mitul Jadeja, special projects manager, Vigilance and Intelligence Research Group, Vigilance and Risk Management of Medicines Adverse drug reactions: prescribing’s twilight zone