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Analgesic efficacy and adverse effects of paracetamol-codeine combination in third molar surgery: a meta-analytic systematic review

Rosa A, Miranda M, Barnaba P, Bollero P, Gargari M, Martelli M

Minerva dental and oral science, 2026

582 participants · 2 citations

Abstract

INTRODUCTION

This systematic review and meta-analysis aimed to assess the analgesic efficacy and adverse event profile of paracetamol combined with codeine for managing postoperative pain following third molar surgery.

EVIDENCE ACQUISITION

A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane Library to identify randomized controlled trials comparing paracetamol + codeine with placebo or other analgesics. Data on pain reduction, rescue medication use, and adverse effects were extracted and pooled using a random-effects model. Odds ratios (OR) and numbers needed to treat (NNT) or harm (NNH) were calculated.

EVIDENCE SYNTHESIS

Six RCTs involving 582 patients met inclusion criteria. The paracetamol-codeine combination significantly reduced postoperative pain and delayed the need for rescue medication (OR=0.45, 95% CI 0.30-0.68). However, adverse events were common, with drowsiness (25%, NNH=7), nausea (18%, NNH=11), and dizziness (12%, NNH=15) being the most frequently reported.

CONCLUSIONS

Paracetamol + codeine provides effective postoperative analgesia for third molar surgery, especially in patients contraindicated for NSAIDs. Clinicians should consider the increased risk of sedation and gastrointestinal symptoms when prescribing this combination, and educate patients accordingly.

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 582 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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