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Associated Topics

Evidence supports the use of a single dose of acetaminophen with codeine for moderate to severe pain reduction.

Carlos Flores-Mir DDS, DSc, FRCD(C); Analia Veitz-Keenan DDS .


Systematic Review Conclusion

A single dose of acetaminophen plus codeine provides clinical useful levels of pain relief in patients with moderate to severe post –operative pain.

Critical Summary Assessment

This systematic review represents an update of a previously published Cochrane Review and it follows general accepted rules about how to conduct a systematic review of the available evidence. A good body of high quality double-blinded trials were identified that strongly support the auhors conclusions.

Evidence Quality Rating

Good Evidence

Structured Abstract

Clinical Questions:

In patients that have undergone a surgical procedure and are under moderate to severe pain, does a single dose of acetaminophen plus codeine compared to placebo or acetaminophen alone provide a clinically significant efficient relief of the acute postoperative pain level? In patients that have undergone a surgical procedure and are under moderate to severe pain, does a single dose of acetaminophen plus codeine compared to placebo or acetaminophen alone produce less significant adverse events?

Review Methods:

Four major electronic databases were searched up to August 2008. Double blinded randomized controlled trials with at least ten participants per group were selected if they administered a single oral dose of acetaminophen and codeine compared to acetaminophen alone or placebo in patients with moderate to severe acute post operative pain. Studies with multiple doses or cross-over studies were included if data for the first dose/arm could be individualized. No language restrictions were applied and unpublished studies were not searched. Two reviewers independently searched and assessed the quality of the selected studies using a five point scale (Jadad).

Main Results:

Twenty-six randomized controlled trials with 2295 participants met the inclusion criteria (Twelve studies against placebo and fourteen against acetaminophen alone). The most common acetaminophen dose was 600 to 650 mg and for codeine 60 mg. Most of the studies involved patients with dental pain following impacted third molar extraction. The proportion of patients experiencing at least 50% pain relief over 4-6 hours was 43% against 17% for the placebo group and 53% against 41% for the acetaminophen alone group. The NNT for at least 50% pain relief over four to six hours was 3.9 (3.3 to 4.7) compared to placebo and 8.2 (5.0 to 23) compared to acetaminophen alone. Therefore the addition of 60 mg codeine to 600 mg to 650 mg acetaminophen reduced the number of participants requiring rescue medication over four to six hours by 15%. Seven people would need to be treated with the combination to prevent one requiring rescue medication over four to six hours. The adverse effects were mild and transient.


A single dose of acetaminophen plus codeine provides clinical useful levels of pain relief in patients with moderate to severe post –operative pain and it also extended the duration of the analgesia by one hour compared with the same dosage of acetaminophen alone. At higher doses more participants experienced more pain relief but the amount of support data is limited.

Source of Funding:

Anglia and Oxford RHA, UK,NHS Research and Development Health Technology Evaluation Programmes, UK, and European Union Biomed 2 Grant no. BMH4 CT95 0172, UK.


Importance and Context:

After any surgical procedure inflammation and tissue damage occur. Acetaminophen is a widely used over the counter medication and it is the drug of choice in patients for whom NSAID’s are contraindicated, with known hepatotoxicity after long term use. Codeine has limited tolerability due to its adverse effects (nausea, somnolence, dry mouth, constipation and dizziness) and it is known that a small percentage of patients will not get additional benefit with the inclusion of codeine due to lack the enzyme required to transform codeine into morphine.As dental procedures may result in different levels of post-operative pain, a study of the relative efficacy of acetaminophen and codeine in management of moderate to severe pain would be beneficial.

Strengths and Weaknesses of the Systematic Review:

This is a methodologically strong systematic review in which QUOROM guidelines were followed and a sensitivity analysis was completed. Power calculations and transparent randomization procedures were reported for each trial. An assessment of the homogeneity of included studies was reported. Patients withdrawing from studies were followed and reasons were noted. Estimates of relative benefit and risk were calculated with 95% confidence intervals. The review also reports numbers needed to treat (NNT) for efficacy and numbers needed to harm (NNH) for adverse effects. One weakness of the systematic review could be the decision not to search grey literature for unpublished studies.

Strengths and Weaknesses of the Evidence:

Only randomized double blind clinical trials were included which represents the most appropriate study design for the clinical question A large number of studies and participants indicates rigorous data. The high methodological quality, as well as the homogeneity and consistency among included studies leads to a high level of confidence in the evidence reported.

Implications for Dental Practice:

Pain is a common manifestation following surgery. For patients to receive the greatest benefit from analgesics used to manage pain, practitioners should be familiar with the appropriate selection of the medication type and related doses of analgesics. A combination of acetaminophen and codeines seems effective for pain management in patients with moderate-to-severe postsurgical pain. In addition only one extra hour of analgesic effect is obtained.

Critical Summary Publication Date:


These summaries are not intended to, and do not, express, imply, or summarize standards of care, but rather provide a concise reference for dentists to aid in understanding and applying evidence from the referenced systematic review in making clinically sound decisions as guided by their clinical judgment and by patient needs. American Dental Association © 2019