Background: US Food and Drug Administration advisory committees recently made some recommendations to address paracetamol (acetaminophen, APAP)-related toxicity.

Objectives: To study the proportion of APAP users potentially consuming APAP over the currently recommended dosage (4 g/day) and a toxic dosage (10 g/day).  To explore the impact of substituting the APAP strength in combination prescriptions to 325mg on potential APAP overuse patterns.

Methods: Using pharmacy claims data for 2001 to 2008 from IMS LifeLink Health Plans (USA), APAP potential maximum daily dose (PMDD), potential cumulative dose and potential average daily dose (PADD) were calculated annually for APAP users.  The proportion of users with potential APAP use above 4 g/day and 10 g/day are reported.  Analyses were repeated by substituting the maximum APAP strength in combination prescriptions to 325mg.  Ordinary least squares regression was used to detect linear trends in APAP use/overuse.

Results: 790,188 of 2,656,161 study subjects were prescribed APAP in one or more years from 2001 to 2008.  32.62% and 26.84% of the adult APAP users had a PMDD above 4 g/day in 2001 and 2008 while 1.88% and 3.17% had a PMDD above 10 g/day.  If the maximum APAP strength in combination prescriptions was 325mg, the proportion of APAP users with PMDD above 4g would be 14.08% in 2001 and 13.67% in 2008, whereas the proportion of those with PMDD above 10g would be 0.21% and 2.30%, respectively.

Conclusions: About 1 in 4 APAP users has a PMDD above 4g/day, whereas 2 to 3% have a PMDD above 10g based exclusively on prescription data, which is concerning.  These proportions could reduce by over half if the maximum APAP strength in combination prescriptions were 325mg.  Additional monitoring of opioid prescription-patterns, physician and pharmacist cognisance in prescribing APAP-containing combination products, and dose-reduction strategies should be considered to reduce APAP overuse.