Patients experiencing acute pain after surgery, including dental surgery, often require
analgesia. Ideally, the chosen analgesic should have a rapid onset and sustained effect.
Etoricoxib is a new cyclooxygenase-2-selective inhibitor that has demonstrated analgesic
efficacy in the treatment of acute pain with a rapid onset and long-lasting pain relief.
The goal of this study was to determine the analgesic effect of single oral doses
of etoricoxib 60, 120, 180, and 240 mg compared with placebo in the treatment of pain
after dental surgery. Ibuprofen was used as an active control.
This was a randomized, double-blind, parallel-group, single-dose, placebo- and active
comparator-controlled study performed at a single center. It consisted of 3 visits
(prestudy, treatment, and poststudy). Eligible patients were aged > or =16 years with
moderate or severe pain after surgical extraction of > or =2 third molars, of which
> or =1 was an impacted mandibular molar. Patients were assessed over 24 hours and
reported pain intensity and pain relied at 14 predefined time points. Plasma samples
for a pharmacokinetic/pharmacodynamic analysis were collected from a subset of patients
at baseline and the 14 predefined time points. The end points included total pain
relief over 8 hours (TOPAR8, the primary end point), sum of pain intensity difference
over 8 hours, patient's global evaluation of treatment, median time to onset of pain
relief (2-stopwatch method), peak pain relief, and duration of analgesic effect (median
time to use of rescue medication). Adverse events were collected up to 14 days postdose.
Three hundred ninety-eight (63.1% women, 36.9% men; mean age, 21.1 years; 72.1% white,
27.9% other; mean number of third molars removed, 3.5; 65.2% experiencing moderate
pain) were randomly allocated to receive etoricoxib 60 mg (n = 75), etoricoxib 120
mg (n = 76), etoricoxib 180 mg (n = 74), etoricoxib 240 mg (n = 76), ibuprofen 400
mg (n = 48), and placebo (n = 49). All active treatments had significantly greater
overall analgesic effect (TOPAR8) compared with placebo (P < or 0.001). Patients who
received etoricoxib 120 and 180 mg had significantly higher TOPAR8 scores than those
who received etoricoxib 60 mg ( P < = 0.001) and ibuprofen (P < 0.05 etoricoxib 120
mg; P < or = 0.001 etoricoxib 180 mg). Least-squares mean TOPAR8 scores for etoricoxib
60, 120, 180, and 240 mg, ibuprofen, and placebo were 16.0, 22.0, 23.5, 20.7, 18.6,
and 5.2, respectively. The median time to onset of analgesia was 24 minutes for etoricoxib
120, 180, and 240 mg, and 30 minutes for etoricoxib 60 mg and ibuprofen. There were
no significant differences in the onset of analgesia between etoricoxib 120, 180,
and 240 mg and ibuprofen. The duration of analgesic effect was >24 hours for etoricoxib
120, 180, and 240 mg, and 12.1 hours for etoricoxib 60 mg. The duration of effect
was significantly longer with all 4 etoricoxib doses compared with ibuprofen (10.1
hours; P < 0.05 etoricoxib 60 mg; < or = 0.001etoricoxib 120, 180, and 240 mg) and
compared with placebo (2.1 hours; P < = 0.001). In the pharmacokinetic/pharmacodynamic
analysis (n approximately 120), there was a linear relationship between plasma etoricoxib
concentrations and pain relief scores up to the maximum observed concentration, followed
by a decline in plasma concentrations with persistent analgesia. The most common adverse
events were postextraction alveolitis and nausea.
In this dose-ranging study, etoricoxib 120 mg was determined to be the minimum dose
that had maximal efficacy in patients with moderate to severe acute pain associated
with dental surgery. Both etoricoxib and ibuprofen were generally well tolerated.