A Population Study of the Frequency of High-Dose Acetaminophen Prescribing and Dispensing

Emergency Medicine, Anesthesiology, and Pharmacology/Toxicology, School of Medicine, University of California, Davis, Veterans Affairs Northern California Health System, Sacramento, CA 95817, USA.
Annals of Pharmacotherapy (Impact Factor: 2.06). 07/2010; 44(7-8):1191-5. DOI: 10.1345/aph.1P012
Source: PubMed


Recurrent intake of 4 g/day or more of acetaminophen has been associated with elevation of serum alanine aminotransferase (ALT) levels in 30-40% of the exposed population and may result in hepatotoxicity.
To describe the frequency that patients are prescribed acetaminophen doses that exceed 4 g/day across a large population.
Using California's Medicaid (Medi-Cal) fee-for-service population, pharmacy claims including over-the-counter (OTC) medications were examined for prescriptions that could result in acetaminophen doses of 4 g/day or more. The period studied, October 2004 through September 2005, was before the Part D pharmacy benefit was available to dually eligible Medicare patients when all prescriptions were covered by the Medi-Cal claims process.
During the pre-Part D evaluation period, approximately 3.27 million beneficiaries were enrolled in the fee-for-service Medi-Cal program. A total of 192,716 (5.9%) were potentially exposed to at least 1 day of 4 g/day or more of acetaminophen. Of those, 769 patients were potentially exposed to at least 1 day of 16 g/day or more. A total of 2664 beneficiaries were dispensed prescriptions and OTC products that, if taken as directed, would have resulted in more than 100 days of acetaminophen doses of 4 g/day or more during the study year.
Despite electronic systems designed to warn dispensing pharmacists of duplications of drug class and cumulative excessive doses, potentially toxic amounts of acetaminophen are commonly prescribed and dispensed to this population. Better systems, increased awareness, and education of patients, prescribers, and pharmacists are needed to reduce this potential toxic exposure.

Download full-text


Available from: Timothy E Albertson
  • Source
    • "Department of Health and Human Services, 2005; http:// This is equal to a high therapeutic dose for humans (.4–6 g/d) (Albertson et al., 2010) and, thus, is often administered to patients receiving APAP for pain management. Such an APAP dose has the potential to activate CAR and increase P-gp functional expression at the BBB, an effect that may lead to significant drug-drug interactions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Effective pharmacological treatment of pain with opioids requires that these drugs attain efficacious concentrations in the central nervous system (CNS). A primary determinant of CNS drug permeation is P-glycoprotein (P-gp), an endogenous blood-brain barrier (BBB) efflux transporter that is involved in brain-to-blood transport of opioid analgesics (i.e., morphine). Recently, the nuclear receptor constitutive androstane receptor (CAR) has been identified as a regulator of P-gp functional expression at the BBB. This is critical to pharmacotherapy of pain/inflammation, as patients are often administered acetaminophen (APAP), a CAR activating ligand, in conjunction with an opioid. Our objective was to investigate, in vivo, the role of CAR in regulation of P-gp at the BBB. Following APAP treatment, P-gp protein expression was increased up to 1.4-1.6-fold in a concentration-dependent manner. Additionally, APAP increased P-gp transport of BODIPY-verapamil in freshly isolated, rat brain capillaries. This APAP-induced increase in P-gp expression and activity was attenuated in the presence of CAR protein inhibitor or transcriptional inhibitor actinomycin D, suggesting P-gp regulation is CAR-dependent. Furthermore, morphine brain accumulation was enhanced by P-gp inhibitors in APAP treated animals, suggesting P-gp mediated transport. A warm water (50°C) tail flick assay revealed a significant decrease in morphine analgesia in animals treated with morphine 3 h or 6 h after APAP treatment as compared to animals treated concurrently. Taken together, our data imply that inclusion of APAP in a pain treatment regimen activates CAR at the BBB and increases P-gp functional expression, a clinically significant drug-drug interaction that modulates opioid analgesic efficacy.
    Full-text · Article · Sep 2013 · Molecular pharmacology
  • Source
    • "Professional and public education initiatives and legislation to limit paracetamol use are increasingly being suggested, in order to limit the potential harm from overuse of paracetamol. [20,28-30] However, only a few population level studies, all using American data, [31,32] have documented the prevalence of paracetamol use exceeding the dosage limits recommended by regulatory bodies. The objective of this study is to provide population-based Canadian data on the prevalence of high-dose paracetamol use from prescribed paracetamol/opioid combinations. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Paracetamol (acetaminophen) is generally considered a safe medication, but is associated with hepatotoxicity at doses above doses of 4.0 g/day, and even below this daily dose in certain populations. The Nova Scotia Prescription Monitoring Program (NSPMP) in the Canadian province of Nova Scotia is a legislated organization that collects dispensing information on all out-of-hospital prescription controlled drugs dispensed for all Nova Scotia residents. The NSPMP provided data to track all paracetamol/opioids redeemed by adults in Nova Scotia, from July 1, 2005 to June 30, 2010. Trends in the number of adults dispensed these prescriptions and the numbers of prescriptions and tablets dispensed over this period were determined. The numbers and proportions of adults who filled prescriptions exceeding 4.0 g/day and 3.25 g/day were determined for the one-year period July 1, 2009 to June 30, 2010. Data were stratified by sex and age (<65 versus 65+). Both the number of prescriptions filled and the number of tablets dispensed increased over the study period, although the proportion of the adult population who filled at least one paracetamol/opioid prescription was lower in each successive one-year period. From July 2009 to June 2010, one in 12 adults (n = 59,197) filled prescriptions for over 13 million paracetamol/opioid tablets. Six percent (n = 3,786) filled prescriptions that exceeded 4.0 g/day and 18.6% (n = 11,008) exceeded 3.25 g/day of paracetamol at least once. These findings exclude non-prescription paracetamol and paracetamol-only prescribed medications. A substantial number of individuals who redeem prescriptions for paracetamol/opioid combinations may be at risk of paracetamol-related hepatotoxicity. Healthcare professionals must be vigilant when prescribing and dispensing these medications in order to reduce the associated risks.
    Full-text · Article · Jun 2012 · BMC Clinical Pharmacology

  • No preview · Article · Oct 2010 · Annals of Pharmacotherapy
Show more