Acute overdose with sustained release drug formulations. Perspectives in treatment

Acute overdose with sustained release formulations presents special problems for the health care system. Proper management requires a basic understanding of the pharmacokinetic and pharmacodynamic characteristics of the drugs taken in overdose because different techniques employed by the manufacturers to produce sustained release formulations lead to differences in these characteristics in comparison with conventional formulations. In general, with sustained-release formulations, there is a prolongation of the time for the patient to manifest toxicity ('preclinical phase'), as well as the period of high drug concentrations and clinical toxicity ('toxic phase') and the resolution phase (clinical improvement with declining drug concentrations). Continued drug absorption over a prolonged period alters the normal drug concentration-time profile. The prolonged absorption half-life may appear as an increase in elimination half-life, even though the clearance of the drug stays the same. Gastrointestinal decontamination is extremely important in the management of overdose with sustained release formulations. We advocate an aggressive decontamination approach to management, especially in the preclinical phase. With a history of potentially toxic ingestion of an adsorbable drug, a charcoal stool following administration of oral activated charcoal should be a minimum requirement for discharge of the patient. Gastrointestinal decontamination is critical in the preclinical and the toxic phases and may be of value during the resolution phase until the drug concentrations decline to the therapeutic range.