title: Early presentation following overdose of modified-release paracetamol (Panadol Osteo) with biphasic and prolonged paracetamol absorption.
abstract: BACKGROUND
  Panadol Osteo (GlaxoSmithKline) is a modified-release paracetamol formulation marketed in Australia and New Zealand, comprising 33% immediate and 66% sustained-release fractions. In overdose, absorption may be delayed and the paracetamol treatment nomogram can miss potentially toxic paracetamol concentrations if only one serum estimate is taken. We report a massive ingestion of Panadol Osteo with biphasic, prolonged absorption requiring extended treatment with N-acetylcysteine.
  
  
  METHODS
  A 72-year-old female presented 2 hours after ingesting 119x665 mg (1 g/kg) of Panadol Osteo and 5x30 mg mirtazepine. The patient was drowsy (GCS14). Activated charcoal was not administered. Her pulse was 70 bpm, BP 149/63 mmHg with an unremarkable physical examination. Two-hour paracetamol concentration was 2628 micromol/L falling to 2216 micromol/L, 4 hours post-ingestion. Admission acid-base status and liver function were normal. N-acetylcysteine was commenced using the standard 21-hour intravenous protocol and continued for 5 days (total dose 700 mg/kg) until paracetamol concentrations were undetectable. Serum paracetamol peaked a second time, 12 hours post-ingestion, at 3040 micromol/L and paracetamol absorption continued for 35 hours post-ingestion. Despite early administration of N-acetylcysteine, serum AST/ALT peaked at 384 and 541 IU/L on day 3 with normal coagulation profile.
  
  
  CONCLUSIONS
  Massive ingestion of modified-release paracetamol (Panadol Osteo) may result in biphasic and prolonged paracetamol absorption requiring extended administration of N-acetylcysteine. Current intravenous dosing regimens may not provide enough N-acetylcysteine to effectively metabolise paracetamol to non-toxic adducts.
authors.affiliation: Clinical and Experimental Toxicology Unit, Department of Emergency Medicine, Prince of Wales Hospital, Randwick, NSW, 2031, Australia. Andis.graudins@unsw.edu.au
authors.forename: Andis
authors.initials: A
authors.lastname: Graudins
authors.forename: Hanh Ngoc
authors.initials: HN
authors.lastname: Pham
authors.forename: Chris
authors.initials: C
authors.lastname: Salonikas
authors.forename: Daya
authors.initials: D
authors.lastname: Naidoo
authors.forename: Betty
authors.initials: B
authors.lastname: Chan
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000111:Acetylcysteine / Q000627:therapeutic use*; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D001219:Aspartate Aminotransferases / Q000097:blood; D003692:Delayed-Action Preparations; D062787:Drug Overdose; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous
chemical_list: D018712:Analgesics, Non-Narcotic; D003692:Delayed-Action Preparations; D016166:Free Radical Scavengers; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000111:Acetylcysteine