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Opioid-Paracetamol Prescription Patterns and Liver Dysfunction

A Retrospective Cohort Study in a Population Served by a US Health Benefits Organization

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Abstract

Background: Paracetamol (acetaminophen) is the most common cause of acute liver failure (ALF). ALF attributed to paracetamol is most often associated with the following features: an unintentional overdose, a single product, an opioid-paracetamol combination, duration of <7 days, and a median dose of 7.5 g/day. Currently, the recommended maximum daily dose of paracetamol is 4 g.

Objectives: The aims of the study were to determine opioid-paracetamol prescription patterns, including prescriptions exceeding the recommended dose of paracetamol (4 g/day) [prescriptions and beneficiaries]; examine factors associated with receiving opioid-paracetamol prescriptions in excess of paracetamol 4 g/day; and evaluate opioid-paracetamol prescription patterns for beneficiaries with liver dysfunction.

Methods: A retrospective cohort study examining prescription data of 4.8 million beneficiaries from a US health benefits organization from 1 January 2009 through 31 December 2009. The main outcomes examined were daily paracetamol dose and liver dysfunction.

Results: A large proportion (8.1%) of the 5.3 million prescriptions for opioid-paracetamol exceeded the recommended maximum daily dose of paracetamol (4 g/day), putting over one-quarter of a million (255 123 [18.9%]) of the 1.35 million beneficiaries receiving an opioid-paracetamol prescription at risk of toxicity. The most frequently prescribed products that exceeded paracetamol dose guidelines contained dextropropoxyphene and hydrocodone. Multiple factors, including type of product (i.e. dextropropoxyphene or oxycodone-containing), geographical location (Midwest), strength of the paracetamol in the opioid-paracetamol product (>325 mg) and prescriber specialty (dentist, physician assistant), were associated with high-dose paracetamol prescriptions. Liver dysfunction was diagnosed in 3818 cases, and 23.4% of these beneficiaries received an opioid-paracetamol prescription in the 90 days prior to the liver dysfunction diagnosis.

Conclusions: Although most opioid-paracetamol prescriptions are written and dispensed for <4 g/day of paracetamol, a significant portion of beneficiaries are being prescribed and dispensed excessive doses of paracetamol. Efforts to curtail this practice may involve provision of prescriber and pharmacist education, utilization of benefit manager systems to flag excessive dosing or that require confirmation of dosing, and implementation of US FDA recommendations supported by these data.

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Acknowledgements

All authors have no financial disclosures, and no funding/ support was received for this study. Drs Lilian Ndehi, Yihua Xu and Jane Stacy are employees of Humana, Inc., and Jane Stacy owns stock in Humana, Inc. Jane Mort and Olayinka Shiyanbola have no conflicts of interest to declare that are directly relevant to the content of this study.

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Authors and Affiliations

  1. College of Pharmacy, Avera Health and Science Center, South Dakota State University, Brookings, SD, 57007, USA

    Jane R. Mort (Professor of Pharmacy Practice, Associate Dean for Academic Programs)

  2. College of Pharmacy, South Dakota State University, Sioux Falls, SD, USA

    Olayinka O. Shiyanbola

  3. Competitive Health Analytics, Humana Inc., Louisville, KY, USA

    Lilian N. Ndehi, Yihua Xu & Jane N. Stacy

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  1. Jane R. Mort
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  2. Olayinka O. Shiyanbola
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  3. Lilian N. Ndehi
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  4. Yihua Xu
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  5. Jane N. Stacy
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Correspondence to Jane R. Mort.

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Mort, J.R., Shiyanbola, O.O., Ndehi, L.N. et al. Opioid-Paracetamol Prescription Patterns and Liver Dysfunction. Drug-Safety 34, 1079–1088 (2011). https://doi.org/10.2165/11593100-000000000-00000

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