Controlled release drugs in overdose. Clinical considerations

Abstract

The main characteristic of overdose with controlled release formulations is the delay in presentation and onset of clinical effects. There is a prolonged absorption phase which leads to a delayed time to maximum plasma concentration and usually a prolonged time with levels close to the peak concentration. Absorption may continue for more than 24 hours. Overdose with controlled release formulations of toxic drugs therefore requires a longer period of observation as the onset of symptoms may be as late as 16 to 20 hours after ingestion. Treatment nomograms calculated for standard formulations are not appropriate for controlled release formulations. The optimal gastrointestinal decontamination method is controversial, but in serious overdoses it should include gastric lavage and activated charcoal followed by whole bowel irrigation as a means of clearing whole tablets from the gastrointestinal tract. Pharmacobezoar formation should be suspected if, despite apparently effective gastrointestinal decontamination, there is evidence of continuing absorption. These are best diagnosed with endoscopy and the treatment options include endoscopic removal, whole bowel irrigation and surgery.