Both paracetamol and ibuprofen are commonly used analgesics for the relief of pain following the surgical removal
of lower wisdom teeth (third molars). In 2010, a novel analgesic (marketed as Nuromol) containing both paracetamol and ibuprofen
in the same tablet was launched in the United Kingdom, this drug has shown promising results to date and we have chosen to
also compare the combined drug with the single drugs using this model. In this review we investigated the optimal doses of
both paracetamol and ibuprofen via comparison of both and via comparison with the novel combined drug. We have taken into
account the side effect profile of the study drugs. This review will help oral surgeons to decide on which analgesic to prescribe
following wisdom tooth removal.
To compare the beneficial and harmful effects of paracetamol, ibuprofen
and the novel combination of both in a single tablet for pain relief following the surgical removal of lower wisdom teeth,
at different doses and administered postoperatively.
We searched the Cochrane Oral Health Group'sTrials
Register (to 20 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue
4); MEDLINE via OVID (1946 to 20 May 2013); EMBASE via OVID (1980 to 20 May 2013) and the metaRegister of Controlled Trials
(to 20 May 2013). We checked the bibliographies of relevant clinical trials and review articles for further studies. We wrote
to authors of the identified randomised controlled trials (RCTs), and searched personal references in an attempt to identify
unpublished or ongoing RCTs. No language restriction was applied to the searches of the electronic databases.
Only randomised controlled double-blinded clinical trials were included. Cross-over studies were included provided
there was a wash out period of at least 14 days. There had to be a direct comparison in the trial of two or more of the trial
drugs at any dosage. All trials used the third molar pain model.
Data collection and analysis
All trials identified
were scanned independently and in duplicate by two review authors, any disagreements were resolved by discussion, or if necessary
a third review author was consulted. The proportion of patients with at least 50% pain relief (based on total pain relief
(TOTPAR) and summed pain intensity difference (SPID) data) was calculated for all three drugs at both two and six hours postdosing
and meta-analysed for comparison. The proportion of participants using rescue medication over both six and eight hours was
also collated and compared. The number of patients experiencing adverse events or the total number of adverse events reported
or both were analysed for comparison.
Seven studies were included, they were all parallel-group
studies, two studies were assessed as at low risk of bias and three at high risk of bias; two were considered to have unclear
bias in their methodology. A total of 2241 participants were enrolled in these trials.
Ibuprofen was found to be
a superior analgesic to paracetamol at several doses with high quality evidence suggesting that ibuprofen 400 mg is superior
to 1000 mg paracetamol based on pain relief (estimated from TOTPAR data) and the use of rescue medication meta-analyses. The
risk ratio for at least 50% pain relief (based on TOTPAR) at six hours was 1.47 (95% confidence interval (CI) 1.28 to 1.69;
five trials) favouring 400 mg ibuprofen over 1000 mg paracetamol, and the risk ratio for not using rescue medication (also
favouring ibuprofen) was 1.50 (95% CI 1.25 to 1.79; four trials).
The combined drug showed promising results, with
a risk ratio for at least 50% of the maximum pain relief over six hours of 1.77 (95% CI 1.32 to 2.39) (paracetamol 1000 mg
and ibuprofen 400 mg) (one trial; moderate quality evidence), and risk ratio not using rescue medication 1.60 (95% CI 1.36
to 1.88) (two trials; moderate quality evidence).
The information available regarding adverse events from the studies
(including nausea, vomiting, headaches and dizziness) indicated that they were comparable between the treatment groups. However,
we could not formally analyse the data as it was not possible to work out how many adverse events there were in total.
There is high quality evidence that ibuprofen is superior to paracetamol at doses of 200 mg to 512 mg and
600 mg to 1000 mg respectively based on pain relief and use of rescue medication data collected at six hours postoperatively.
The majority of this evidence (five out of six trials) compared ibuprofen 400 mg with paracetamol 1000 mg, these are the most
frequently prescribed doses in clinical practice. The novel combination drug is showing encouraging results based on the outcomes
from two trials when compared to the single drugs.