Early presentation following overdose of modified-release paracetamol (Panadol Osteo) with biphasic and prolonged paracetamol absorption

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.

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.

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.