CONTROLLED-RELEASE DRUGS IN OVERDOSE - CLINICAL CONSIDERATIONS

The main characteristic of overdose with controlled release formulatio ns is the delay in presentation and onset of clinical effects. There i s a prolonged absorption phase which leads to a delayed time to maximu m plasma concentration and usually a prolonged time with levels close to the peak concentration. Absorption may continue for more than 24 ho urs. Overdose with controlled release formulations of toxic drugs ther efore 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 controll ed release formulations. The optimal gastrointestinal decontamination method is controversial, but in serious overdoses it should include ga stric 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 e ffective gastrointestinal decontamination, there is evidence of contin uing absorption. These are best diagnosed with endoscopy and the treat ment options include endoscopic removal, whole bowel irrigation and su rgery.