Why paracetamol (acetaminophen) is a suitable first choice for treating mild to moderate acute pain in adults with liver, kidney or cardiovascular disease, gastrointestinal disorders, asthma, or who are older

Abstract

Acute pain is among the most common reasons that people consult primary care physicians, who must weigh benefits versus risks of analgesics use for each patient. Paracetamol (acetaminophen) is a first-choice analgesic for many adults with mild to moderate acute pain, is generally well tolerated at recommended doses (≤4 g/day) in healthy adults and may be preferable to non-steroidal anti-inflammatory drugs that are associated with undesirable gastrointestinal, renal, and cardiovascular effects. Although paracetamol is widely used, many patients and physicians still have questions about its suitability and dosing, especially for older people or adults with underlying comorbidities, for whom there are limited clinical data or evidence-based guidelines. Inappropriate use may increase the risks of both overdosing and inadequate analgesia. To address knowledge deficits and augment existing guidance in salient areas of uncertainty, we have researched, reviewed, and collated published evidence and expert opinion relevant to the acute use of paracetamol by adults with liver, kidney, or cardiovascular diseases, gastrointestinal disorders, asthma, or/and who are older. A concern is hepatotoxicity, but this is rare among adults who use paracetamol as directed, including people with cirrhotic liver disease. Putative epidemiologic associations of paracetamol use with kidney or cardiovascular disease, hypertension, gastrointestinal disorders, and asthma largely reflect confounding biases and are of doubtful relevance to short-term use (<14 days). Paracetamol is a suitable first-line analgesic for mild to moderate acute pain in many adults with liver, kidney or cardiovascular disease, gastrointestinal disorders, asthma, and/or who are older. No evidence supports routine dose reduction for older people. Rather, dosing for adults who are older and/or have decompensated cirrhosis, advanced kidney failure, or analgesic-induced asthma that is known to be cross-sensitive to paracetamol, should be individualized in consultation with their physician, who may recommend a lower effective dose appropriate to the circumstances.

Keywords:

• Acetaminophen
• acute pain
• older adult (frail)
• liver
• kidney
• gastrointestinal diseases
• asthma
• cardiovascular diseases

Transparency

Declaration of funding

This work was funded by GlaxoSmithKline Consumer Healthcare. GlaxoSmithKline authors conceived the review and were involved in establishing its terms of reference, and selected literature. GlaxoSmithKline employees reviewed manuscript drafts and suggested revisions, but the authors were independent in deciding which content and recommendations to include in their final version.

Declaration of financial/other relationships

John Alchin has received honorarium payments for serving as a member of the GlaxoSmithKline Global Pain Faculty. Arti Dhar and Kamran Siddiqui are employees of GlaxoSmithKline Consumer Healthcare. Paul J. Christo has received honorarium payments for serving as a member of the GlaxoSmithKline Global Pain Faculty, has also been a consultant/advisor to Eli Lilly and Y-mAbs Therapeutics, Inc., and undertakes paid media work via Algiatry, LLC; he receives grant funding from the US National Institute on Aging. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

AD and KS conceived the review. JA and PC advised on the review scope and literature search parameters. All authors revised manuscript drafts for important intellectual content and approved the final version submitted.

Acknowledgements

The authors thank Yen-May Ong and Huw Williams PhD of MIMS, Singapore, and David Neil PhD, (affiliated to MIMS, Singapore, at time of writing), for providing medical writing support, which was funded by GlaxoSmithKline Consumer Healthcare in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).

Notes

i Based on package leaflet for Panadol optizorb, 500 mg film-coated tablets Paracetamol. GlaxoSmithKline Dungarvan Ltd., Ireland. Users should read their own package leaflet, as exact recommendations vary between countries and products.

ii This review defines “episodic” as, short-term use as needed to treat intermittent acute pain episodes (e.g. headache, menstrual), as opposed to uninterrupted long-term use to treat chronic pain conditions (e.g. osteoarthritis).