Evaluation of Fixed-Dose Combinations of Ibuprofen and Acetaminophen in the Treatment of Postsurgical Dental Pain: A Pilot, Dose-Ranging, Randomized Study

Abstract

Introduction: Ibuprofen and acetaminophen provide analgesia via different mechanisms of action and do not exhibit drug-drug interactions; therefore, combining low doses of each may provide greater efficacy without compromising safety.

Objectives: The present study assessed the analgesic efficacy of fixed-dose combinations (FDCs) of ibuprofen/acetaminophen (IBU/APAP) compared with ibuprofen 400 mg and placebo.

Methods: This 12-h, double-blind, proof-of-concept study compared three FDCs of IBU/APAP (200 mg/500 mg, 250 mg/500 mg, and 300 mg/500 mg) with ibuprofen 400 mg and placebo in patients with moderate-to-severe pain following third molar extraction. The primary endpoint was the time-weighted sum of pain relief and pain intensity difference scores from 0 to 8 h after dosing (SPRID[4]0-8). Time to meaningful pain relief (TMPR), duration of pain relief, and adverse events (AEs) were also assessed.

Results: In total, 394 patients were randomized. All active treatments were superior to placebo for SPRID[4]0-8 (all p < 0.001) but not significantly different from ibuprofen 400 mg. Median TMPR with FDCs and ibuprofen (44.5-54.1 and 56.2 min, respectively) was faster than with placebo (> 720 min; all p < 0.001 vs. placebo). Duration of pain relief was similar with the FDCs and ibuprofen 400 mg (9.7 -11.1 h) and longer than with placebo (1.6 h; all p < 0.001). AE incidence was comparable with all treatments.

Conclusion: Each IBU/APAP FDC provided analgesic efficacy comparable to that with ibuprofen 400 mg and superior to that with placebo. Each FDC provided MPR in < 1 h, duration of pain relief > 9 h, and tolerability similar to that with ibuprofen and placebo. CLINICALTRIALS.

Gov registration: NCT01559259.

Conflict of interest statement

David Kellstein is a former employee of Pfizer Consumer Healthcare. Rina Leyva is a current employee of GSK Consumer Healthcare. On 1 August 2019, Pfizer Consumer Healthcare became part of GSK Consumer Healthcare.

Figures

Fig. 1

Patient disposition. APAP acetaminophen, FDC fixed-dose combination, IBU ibuprofen

Fig. 2

Five-point categorical pain relief rating scores over time. APAP acetaminophen, FDC fixed-dose combination, IBU ibuprofen. *p ≤ 0.001 vs. placebo. †p ≤ 0.01 vs. placebo. ‡p ≤ 0.05 vs. placebo. §p ≤ 0.01 vs. IBU 400 mg. IIp ≤ 0.05 vs. IBU 400 mg. ¶p ≤ 0.05 vs. FDC IBU/APAP 200 mg/500 mg

Fig. 3

Mean time-weighted sum of pain relief and pain intensity difference scores. APAP acetaminophen, FDC fixed-dose combination, IBU ibuprofen, SE standard error, SPRID[4] time-weighted sum of pain relief and pain intensity difference scores based on the categorical pain severity rating scale and pain relief scores from 0–2, 0–6, 0–8, and 0–12 h. *p < 0.001 vs. placebo. †p < 0.05 vs. IBU 400 mg

Fig. 4

Kaplan–Meier estimate of time to meaningful pain relief. APAP acetaminophen, IBU, ibuprofen. *p ≤ 0.001 vs. placebo. †p ≤ 0.05 vs. IBU 400 mg

Fig. 5

Kaplan–Meier estimate of time to treatment failure. APAP acetaminophen, FDC fixed-dose combination, IBU ibuprofen. *p ≤ 0.001 vs. placebo