Clinical update on benefit versus risks of oral paracetamol alone or with codeine: still a good option?

Abstract

Background: After decades of worldwide use of paracetamol/acetaminophen as a popular and apparently safe prescription and over-the-counter medicine, the future role of this poorly understood analgesic has been seriously questioned by recent concerns about prenatal, cardiovascular (CV) and hepatic safety, and also about its analgesic efficacy. At the same time the usefulness of codeine in combination products has come under debate.

Methods: Based on a PubMed database literature search on the terms efficacy, safety, paracetamol, acetaminophen, codeine and their combinations up to and including June 2016, this clinical update reviews the current evidence of the benefit and risks of oral paracetamol alone and with codeine for mild-to-moderate pain in adults, and compares the respective efficacy and safety profiles with those of nonsteroidal anti-inflammatory drugs (NSAIDs).

Results: Whereas there is a clear strong association of NSAID use and gastrointestinal (GI) and CV morbidity and mortality, evidence for paracetamol with and without codeine supports the recommended use even in most vulnerable individuals, such as the elderly, pregnant women, alcoholics, and compromised GI and CV patients. The controversies and widespread misconceptions about the complex hepatic metabolism and potential hepatotoxicity have been corrected by recent reviews, and paracetamol remains the first-line nonopioid analgesic in patients with liver diseases if notes of caution are applied.

Conclusion: Due to its safety and tolerability profile paracetamol remained a first-line treatment in many international guidelines. Alone and with codeine it is a safe and effective option in adults, whilst NSAIDs are obviously less safe as alternatives, given the risk of potentially fatal GI and CV adverse effects.

Keywords:

• Adult patients
• analgesic efficacy
• codeine combination
• hepatic failure
• NSAIDs
• paracetamol/acetaminophen
• safety

Transparency

Declaration of funding

This review was not funded.

Declaration of financial/other relationships

H.G.K. has disclosed that he has served as expert adviser for bene-Arzneimittel, Novartis and Boehringer Ingelheim on paracetamol and/or NSAID risk evaluation. He also provided services as congress speaker and/or consultant for Dr. Reddy’s, Grünenthal GmbH, Teva, IBSA, Angelini/CSC, Janssen, and Mundipharma. G.U. has disclosed that he had been a consultant for bene-Arzneimittel GmbH in the past.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.