Paracetamol-induced hepatotoxicity after normal therapeutic doses in the Hong Kong Chinese population.

Introduction: Paracetamol is generally safe at normal therapeutic doses of ≤4 g/day in adults. However, paracetamol-induced hepatotoxicity after normal therapeutic doses use has been reported. We investigated the epidemiology of this adverse drug reaction in the Hong Kong Chinese population.

Methods: This territory-wide retrospective observational study included adult patients with suspected paracetamol-induced hepatotoxicity after normal therapeutic doses use from January 2011 to June 2022. We evaluated the demographic characteristics; paracetamol dose, duration, and reason for use; preexisting hepatotoxicity risk factors; laboratory findings; and their relationship with clinical outcomes.

Results: We identified 76 patients (median age: 74 years, 23 males) with suspected paracetamolinduced hepatotoxicity after normal therapeutic doses use. There were 14 cases with significant clinical outcomes (five deaths and nine cases of acute hepatic failure), with an incidence of 1.2 cases per year. For patients with significant clinical outcomes, they were significantly older (age >80 years), had a lower body weight (<50 kg), exposed to longer durations (>2 days) and higher daily doses (>3 g), and with higher proportion of malnutrition.

Conclusion: Paracetamol-induced hepatotoxicity can occur at normal therapeutic doses in the Hong Kong Chinese population. The identified risk factors are consistent with international guidelines regarding susceptible patients. Considering the widespread local use of paracetamol and low incidence of severe hepatotoxicity, the current dosage recommendations are considered safe for the general population. For susceptible patients, a reduced maximum dose of ≤3 g/day is recommended, with liver function and serum paracetamol monitoring in place.