Age and Ageing Advance Access originally published online on August 22, 2007
Age and Ageing 2007 36(5):582-584; doi:10.1093/ageing/afm090
Prescription of paracetamol-containing medications as indicator of quality of prescribing
SIR—Paracetamol is widely prescribed for mild to moderate pain and pyrexia. It is available as a single ingredient and also in combination with opiate analgesics such as codeine and dihydrocodeine. The recommended dose of paracetamol for adults is 0.5 to 1 g every 4–6 h to a maximum of 4 g in a given 24-h period [1].Hepatotoxicity is rare if doses of paracetamol < 12 g (or 150 mg/kg body weight) are ingested[2] although it is described[3, 4]. Patients with poor nutrition are particularly at risk of hepatotoxicity even at doses within the recommended range[5]. This may be relevant for older people in hospital as the prevalence of malnutrition is known to be high in this population[6]. However, we are not aware of clinical trial evidence to suggest that older people should have a lower recommended dose. In fact, the current recommended dose is not based on randomised controlled trial data. Using a single intravenous dose of 500 mg of paracetamol, Wynne et al. showed paracetamol clearance to decrease with age and frailty[7]. Miners et al. showed that after administering a single oral dose of 1 g of paracetamol the total clearance and clearance by glucuronidation did not change with age although there was a reduction in clearance by sulphation and renal clearance[8]. Interestingly there was no age effect on the cytochrome P450 mediated clearance of the reactive toxic metabolite. This has also been seen in rat studies [9].
While deliberate overdose of paracetamol is well known, inadvertent, iatrogenic over-dosage is less well recognised. The National Sentinel Audit of Evidence Based Prescribing for Older People supported improvements in prescribing by measuring the quality of prescribing practice [10]. We report here on the prescription of paracetamol and paracetamol-containing preparations in 102 hospitals that participated in the audit and give an estimate of the risk of exceeding the recommended dose of paracetamol. The data were collected prior to the withdrawal of Co-Proxamol, dextropropoxyphene in combination with paracetamol, withdrawn in January 2005, because of poorly established efficacy and unacceptable risk of toxicity in overdose [11].
Hospitals in England and Wales were invited to volunteer to participate in the study in 1999 and 102 hospitals agreed. Prescribing data on paracetamol-containing medications were collected from drug charts of 100 consecutive medical in-patients aged 65 years or older on a selected day for each hospital. Data collected included the dose and frequency of all paracetamol containing medications prescribed. The total paracetamol content in milligrams prescribed to patients was evaluated over a 24 h period. We did not collect data on medications actually administered and nurses did not prescribe. Patients were considered to be at risk of overdosage if there was the potential to be administered over 4 g of paracetamol in 24 h.
Data were collected for 9,979 patients. Of these, 9,927 patients had one or more drugs prescribed. Among these patients 6,141 (62%) were prescribed 6,560 medications containing paracetamol. Apart from paracetamol tablets, four combination preparations were prescribed (Table 1). Data to enable estimation of total dosage was complete for only 6,060 patients prescribed 6,465 medications containing paracetamol (Table 2). There was a potential risk of a paracetamol overdosage for 732/6,060 (12%) of patients prescribed medication containing paracetamol. The risk of the potential for overdosage increased with the number of paracetamol-containing medications prescribed per patient. The percentage of patients at risk of potential overdosage was low (7%) when only one paracetamol-containing medication was prescribed. However, the risk increased dramatically to 90% when two paracetamol-containing medications were prescribed and to 100% with three or more paracetamol-containing medications (Table 2). Data were collected a year later in the second loop of the audit cycle and no significant changes were found.
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Discussion
This study demonstrates that medical in-patients aged 65 years or older are at potential risk, through suboptimal prescribing, of being administered paracetamol exceeding the recommended therapeutic dose. The main problems were: (i) failure to specify the dose frequency; and (ii) prescribing more than one paracetamol-containing medication.
Although this study was conducted prior to the withdrawal of Co-Proxamol we do not expect the situation to have changed much since. As paracetamol is available in a number of compound analgesic preparations, a common error is to co-prescribe paracetamol with a compound analgesic containing paracetamol and exceed the recommended limit. Recently, SUREMED, an anonymous self-reporting scheme for medication errors [12, 13] alerted prescribers in King's College Hospital of such duplicate dose errors (internal communication). The alert advised that when prescribing analgesics which patients bring into hospital, doctors need to check the paracetamol content and review the current medication chart to ensure that no other paracetamol-based analgesics are prescribed.
The main limitation of our study was the unavailability of data on clinical endpoints and medications administered, which the audit was not designed to measure. While data were collected for 100 consecutive patients over the age of 65 on medical wards on a selected day for each hospital, we do not have data on the number of all inpatients at the time of audit. Over 98% of the patients prescribed paracetamol or paracetamol-containing medication had dosage data available. We did not feel that we could make a meaningful comparison between patients with and without dosage data because the latter group had only 81 patients compared with 6,040 with dosage data available.
Paracetamol is a popular first-line choice for management of pain and pyrexia in patients of all ages. When used at recommended doses it seldom causes adverse events [14, 15]. To reduce the risk of exceeding the recommended dose of paracetamol prescribers should avoid prescribing the drug as more than one preparation. There is no rationale for more than two preparations to be prescribed concurrently. In addition, prescribers should not rely on those who administer medicines to quantify the total dosage of potentially harmful drugs. The prescription of multiple preparations of paracetamol can be used as a marker of quality of prescribing. As mentioned earlier in this paper, there is no evidence to suggest a lower recommended dose of paracetamol for older people. The prevalence of prescriptions allowing the administration of greater than 4 g of paracetamol in a 24 h period can be used to reflect the risk of iatrogenic over-dosage in adult patients in general.
- Paracetamol is commonly prescribed as a single ingredient or as a compound analgesic.
- The recommended maximum dose of paracetamol for adults is 4 g in a given 24-h period.
- This study showed that the risk of exceeding this dose is increased dramatically when more than one paracetamol-containing medication is prescribed.
- The prevalence of prescriptions allowing the administration of greater than 4 g of paracetamol in a 24 h period can be used to reflect the quality of prescribing in hospital in-patients.
None
Acknowledgements
We thank the hospitals that participated in the study. This work was undertaken by the Royal College of Physicians' Clinical Effectiveness and Evaluation Unit and the Clinical Age Research Unit of the Department of Clinical Gerontology, King's College Hospital, who received funding from the National Institute of Clinical Excellence. The views expressed in this publication are those of the authors.
1 Clinical Age Research Unit, King's College Hospital, Bessemer Road, London SE5 9PJ, UK
2 Department of Healthcare of Older People, Kent and Canterbury Hospital, Canterbury, Kent CT1 3 NG, UK
3 Clinical Effectiveness and Evaluation Unit, Royal College of Physicians, 11 St Andrew's Place, Regents Park, London NW1 4LE, UK
* To whom correspondence should be addressed E-mail: Juliet.manyemba{at}kch.nhs.uk
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