Current Drug Safety, 2013, 8, 203-206
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Missed Paracetamol (Acetaminophen) Overdose Due to Confusion Regarding Drug Names David G. Hewett1, Jennifer Shields2 and W. Stephen Waring*,1 1
Acute Medical Unit, York Teaching Hospital NHS Foundation Trust, UK
2
Emergency Department, York Teaching Hospital NHS Foundation Trust, UK Abstract: Immediate management of drug overdose relies upon the patient account of what was ingested and how much. Paracetamol (acetaminophen) is involved in around 40% of intentional overdose episodes, and remains the leading cause of acute liver failure in many countries including the United Kingdom. In recent years, consumers have had increasing access to medications supplied by international retailers via the internet, which may have different proprietary or generic names than in the country of purchase. We describe a patient that presented to hospital after intentional overdose involving ‘acetaminophen’ purchased via the internet. The patient had difficulty recalling the drug name, which was inadvertently attributed to ‘Advil’, a proprietary non-steroidal anti-inflammatory drug. The error was later recognised when the drug packaging became available, but the diagnosis of paracetamol overdose and initiation of acetylcysteine antidote were delayed. This case illustrates the benefit of routinely measuring paracetamol concentrations in all patients with suspected poisoning, although this is not universally accepted in practice. Moreover, it highlights the importance of the internet as a source of medications for intentional overdose, and emphasises the need for harmonisation of international drug names to improve patient safety.
Keywords: Acetaminophen, analgesic, drug name, drug nomenclature, drug safety, generic drug, paracetamol, proprietary drug. INTRODUCTION Over recent years, medications have become increasingly accessible from international retailers using the internet. Few data are available concerning the extent to which purchasers are knowledgeable about the active content of some of these medications, and little information is available concerning the extent of internet-sourced medications or the impact on patient outcomes. Paracetamol remains an important means of intentional drug overdose and, for example, is involved in around 40% of self-poisoning cases that present to hospital in the United Kingdom [1]. There has been a substantial investment in public health strategies to minimise harm associated with paracetamol, including legislation to limit pack size and the number of tablets that may be purchased in a single transaction [2]. In addition, regulatory guidance ensures that drug packaging clearly indicates products that contain paracetamol, to minimise the risk of accidentally coadministering multiple products. The formulation and presentation of medications purchased from international retailers may differ between the countries of purchase and supply, and patients might not readily identify products as containing paracetamol if they are labelled with unfamiliar generic or proprietary names. This present report describes a patient in the United Kingdom that presented to hospital after overdose involving ‘acetaminophen’ purchased from an internet-based retailer. The patient was unaware that the analgesic he purchased contained paracetamol, and difficulty *Address correspondence to this author at the Acute Medical Unit, York Hospital, Wigginton Road, York, YO31 8HE, UK; Tel: +44(0)1904 726276; E-mail:
[email protected]
1574-8863/13 $58.00+.00
ascertaining the correct drug name led to delays in identifying that he had taken a paracetamol overdose. CASE REPORT A 20-year-old male student presented to the Emergency Department 4 hours after intentional overdose involving multiple medications over 1 to 2 hours. He claimed to have purchased a number of drugs via the internet, including citalopram, Coricidin® (a fixed dose combination of dextromethorphan and chlorpheniramine), and an analgesic that he thought began with ‘ad...’. No drug packaging was available. The treating clinician sought advice from the duty pharmacist who suggested that the analgesic might have been Advil®, a brand of ibuprofen. The patient specifically denied ingestion of paracetamol, ethanol, or other substances. Past history included asthma, depression, and two past overdose episodes several years before. His only regular medication was fluoxetine 20 mg daily, and he usually drank 12-14 units ethanol per week (120-140 mL). He denied recent recreational drug use, but claimed to have used cannabis, ketamine, and ecstacy in the past. Initial examination found the patient slightly agitated, pupils were both 4 mm and reactive, pulse 102 min-1, blood pressure 101/72 mmHg, respiratory rate 14 min-1, and cardiorespiratory and neurological examination normal. Resting electrocardiograph showed normal intervals: PR=148 ms, QRS=101 ms, QT corrected by Bazett’s formula=320 ms. Plain chest radiograph, serum electrolytes, lactate, and creatine kinase, and coagulation were normal; alanine transaminase was 56 U/L (normal reference 0 to 45 U/L), other liver biochemistry tests were normal. Urine was © 2013 Bentham Science Publishers
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negative for the presence of methadone metabolites, monacyl-morphine, amphetamine, benzodiazepines, cannabis, cocaine, and opioids. In the United Kingdom, TOXBASE® is the standard resource for poisoning management, provided by the National Poisons Information Service. This includes providing clinical advice by telephone in cases of complex paracetamol overdose [3]. The database entry for Advil (ibuprofen) toxicity was printed and filed in the patient case records, which recommends monitoring kidney and liver function. Therefore, liver biochemistry was rechecked at 16 hours post-ingestion and showed alanine transaminase had increased to 80 U/L. A further check at 38 hours was 513 U/L, and serum paracetamol concentrations were confirmed in the initial hospital sample as 38 mg/L. The patient later confirmed that he had ingested 30 acetaminophen tablets; a relative retrieved the empty drug packaging, which made no mention of paracetamol as an ingredient. Intravenous acetylcysteine was commenced for suspected paracetamol poisoning, and alanine transaminase activity increased modestly, and then significantly improved (Fig. 1). Soon after, the patient was considered fit for discharge by the medical and psychiatry teams. DISCUSSION This case presents a hazard related to supply of international medicinal products with unfamiliar names, and alerts clinicians to the possibility that patients might use the internet as a means of obtaining less familiar products. Paracetamol overdose had not been recognised at the time of presentation to hospital, in large part due to confusion regarding drug names by the patient and treating clinician. Existing guidelines advise that paramedics in the United Kingdom should collect all suspected drugs or substances for identification at hospital, although this may not always be feasible [4]. The diagnosis would have been established sooner if the patient had presented to hospital with drug packaging, and relatives should be encouraged to bring this
Hewett et al.
if possible. Some institutions advocate routine paracetamol tests in all overdose patients, although there is some international variation in practice. Routine determination of paracetamol concentration in the Emergency Department would have allowed earlier detection in this case. However, prevailing guidelines in the United Kingdom state that paracetamol concentrations should be checked only if there is clinical suspicion of ingestion or the history is unclear [5]. Existing studies indicate that it is rare to detect paracetamol in patients that deny taking it, although the present case indicates a weakness of this approach [6, 7]. Routine laboratory measurement of paracetamol might be considered appropriate in all overdose patients, at least in countries where is commonly encountered. Paracetamol-protein adducts may be detected even after paracetamol concentrations become undetectable, and provide an important biomarker in patients that present late after overdose [8-10]. Paracetamol (acetaminophen) is involved in around 40% of intentional overdose episodes in many countries including the United Kingdom, and remains the leading cause of death or transplantation from acute liver failure [11-13]. Initial clinical management depends on the stated paracetamol dose and interval after ingestion [14-16]. Acetaminophen is a generic drug name that is approved in the United States, Canada, and certain other countries, but the term is seldom encountered in the United Kingdom, Europe, or other countries where the approved generic name is paracetamol. In the United States, the Food and Drug Administration found that a major hazard causing unintentional paracetamol deaths was the wide variety of over the counter products containing paracetamol and that consumers might fail to recognise the paracetamol content and risks of taking two or more products concomitantly [17]. Clinicians might not recognise the paracetamol content of international preparations, even if labelled as containing acetaminophen, posing a risk of inadvertent co-prescribing and toxicity. This includes many fixed dose combination products, for example
Fig. (1). Alanine transaminase (triangle, normal reference 0-45 U/L) and prothrombin time (square, normal reference 9-10 sec) at various intervals after intentional overdose.
Paracetamol Nomenclature
Coricidin® or Anadin Extra®. Meanwhile it may be difficult for regulatory authorities to effectively communicate these risks to prescribers [18]. Internet-based retailers are not subject to uniform international regulations, but are subject to internal policies regarding the sale of medications. Further studies are needed to determine the extent to which overdose patients may obtain medications, including paracetamol via the internet Many products that enjoy ‘over the counter’ (OTC) status in one country may be bought and sold freely to customers elsewhere, with no linkage to patient health records. An enormous public health campaign has recently been undertaken in the United Kingdom and elsewhere to raise awareness of paracetamol-containing products so as to minimise risks of unintentional overdose, for example involving cough and cold remedies. Novel means of access to acetaminophen branded products, coupled with a lack of awareness of their content by both patients and prescribers further increase the risks of inadvertent paracetamol toxicity. Legislation introduced in the United Kingdom in 1998 to restrict the number of paracetamol-containing products that could be purchased in a single transaction has lessened harm as a consequence of intentional paracetamol overdose [19]. However, international sellers based in other countries do not appear to be restricted in their ability to supply medications to customers in the United Kingdom and, at the time of writing, it is possible to purchase one thousand 500 mg acetaminophen tablets for $17.99 (USD) in a single transaction, equivalent to 125 times the recommended maximum adult daily dose. CONCLUSION The propensity for differing international drug names to cause confusion and drug error has previously been described, including the risk of accidental overdose [20-22]. Some steps have already been taken towards international harmonisation, most notably those driven by the World Health Organisation International Non-proprietary Name (INN) program, which was established in 1953 [23]. Nonetheless, this has been only partially successful, and significant international differences exist amongst several commonly prescribed agents (Table 1). The risk of drug error falls into three broad areas: (1) differing generic drug names between countries, (2) confusion between generic and brand names, with guidance favouring prescribing by brand for particular drugs, e.g. antiepileptics and long-acting formulations, and (3) different brand names containing the same drug that might inadvertently be co-prescribed. Sustained effort by regulatory authorities is needed to achieve greater harmonisation of international names, and to address the new challenges arising from internet-based medication sales. Public health bodies need to consider steps to raise consumer awareness that acetaminophen is synonymous with paracetamol to minimise the risks of inadvertent drug toxicity arising inadvertent combination with other paracetamol-containing preparations. Prescribers should be alert to medications obtained without prescription that may have different international names and presentations.
Current Drug Safety, 2013, Vol. 8, No. 3
Table 1.
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Some Examples of Different Generic Names for Commonly Prescribed Drugs Comparing the International Non-Proprietary Name (INN), British Approved Names (BAN), and United States Adopted Names Council (USAN) INN
BAN
USAN
Chlorphenamine
Chlorpheniramine*
Chlorphenamine
Dextropropoxyphene
Dextropropoxyphene
Propoxyphene*
Mesalazine
Mesalazine
Mesalamine*
Norepinephrine
Adrenaline*
Norepinephrine
Paracetamol
Paracetamol
Acetaminophen*
Pethidine
Pethidine
Meperidine*
Salbutamol
Salbutamol
Albuterol*
*Denotes different from INN.
CONFLICT OF INTEREST The authors confirm that this article content has no conflict of interest. ACKNOWLEDGEMENTS We would like to express our sincere gratitude to the patient for allowing us present the details of his case in this report. The case details have been submitted to the Medicines and Healthcare Products Regulatory Authority in the United Kingdom, and Institute for Safe Medications Practices in the United States. PATIENT CONSENT Declared none. REFERENCES [1]
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Received: June 4, 2013
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Accepted: June 27, 2013
