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The Safety Profile of Sustained Release Paracetamol During Therapeutic Use and Following Overdose

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Abstract

Sustained release (SR) formulations of paracetamol (acetaminophen) have been introduced in several countries to provide lasting pain relief and reduced risk of rebound pain. However, few studies have evaluated the safety of paracetamol SR formulations.

To assess the available published safety data regarding SR formulations of paracetamol, the EMBASE and MEDLINE databases were searched from 1980 to June 2003 for published worldwide human experience with paracetamol SR formulations. All publications that included any information about ingestion of any paracetamol SR formulation were systematically reviewed and abstracted by trained staff. The literature searches returned a total of 14 references containing safety data on paracetamol SR. In addition, the Toxic Exposure Surveillance System (TESS) of the American Association of Poison Control Centers (AAPCC) database was searched for human exposure cases. The TESS database yielded 3003 cases from 1994 to 2002 that involved a paracetamol SR product.

The available information indicates that the adverse event and safety profile of paracetamol SR is very similar to immediate release (IR) formulations of paracetamol. During therapeutic use, minor effects such as gastrointestinal upset and headache may occur. The rate of these effects varies substantially among studies but overall does not appear to be different between the SR and IR formulations of paracetamol. Overdose with paracetamol SR is expected to cause liver injury similar to overdose with IR formulations. The number of human exposure cases has increased since introduction of the SR formulation; however, sales of the SR formulation amounted to 7.5% of all paracetamol sales but accounted for 2.5% of the cases reported to poison centres. There were two deaths recorded in the TESS database: both were the result of multiple drug ingestion. No cases of death or unusual types of toxicity have been described from an overdose of paracetamol SR alone.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

This analysis was supported by a grant from GlaxoSmithKline. Denver Health Rocky Mountain Poison and Drug Center conducts research for McNeill Consumer & Specialty Pharmaceuticals (manufacturer of Tylenol®) and Cumberland Pharmaceuticals Inc. (manufacturer of Acetadote®).

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Authors and Affiliations

  1. Department of Surgery (Emergency Medicine), Rocky Mountain Poison and Drug Center, Denver Health, University of Colorado Health Sciences Center, 777 Bannock Street, Denver, MC 0180, Colorado, 80204, USA

    Richard C. Dart, Jody L. Green & Gregory M. Bogdan

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  1. Richard C. Dart
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  2. Jody L. Green
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  3. Gregory M. Bogdan
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Correspondence to Richard C. Dart.

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Dart, R.C., Green, J.L. & Bogdan, G.M. The Safety Profile of Sustained Release Paracetamol During Therapeutic Use and Following Overdose. Drug-Safety 28, 1045–1056 (2005). https://doi.org/10.2165/00002018-200528110-00005

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