Efficacy and safety of a fixed‐dose combination of ibuprofen and caffeine in the management of moderate to severe dental pain after third molar extraction

Abstract

BackgroundIbuprofen is an effective analgesic treatment with a ceiling effect at doses above 400 mg. This study compared the combination of ibuprofen 400 mg and caffeine 100 mg with ibuprofen 400 mg monotherapy, caffeine and placebo in the analgesic treatment of moderate to severe acute dental pain following third molar extraction.MethodsPhase III, active‐/placebo‐controlled, double‐blind, single‐centre, two‐stage, parallel‐group study in adult patients with at least moderate baseline pain intensity. Primary endpoint was defined as the time‐weighted sum of pain relief and pain intensity difference over 8 h (SPRID0–8 h), secondary endpoints included duration of pain relief, time to meaningful pain relief and more.Results N = 748 patients were enrolled and N = 562 treated. Mean baseline pain intensity was 7.7 on a 0–10 numerical rating scale. Analysis of SPRID0–8 h demonstrated superior analgesic effects for a single dose of ibuprofen/caffeine versus ibuprofen, caffeine and placebo over 8 h, rescue medication in this stage was requested by more patients on ibuprofen (32.5%) than on ibuprofen/caffeine (16.0%). Median time to meaningful pain relief was shorter for ibuprofen/caffeine (1.13 h) compared with ibuprofen (1.78 h; p = 0.0001). More patients on ibuprofen/caffeine than on ibuprofen reported meaningful pain relief. Adverse events were infrequent and mostly mild or moderate across treatment groups. Tolerability was rated as ‘very good’ or ‘excellent’ by most patients in both treatment groups.ConclusionThis study demonstrated clinically relevant superiority of ibuprofen/caffeine over monotherapy with ibuprofen in patients with acute dental pain. All treatments were well tolerated.SignificanceThis trial showed superior efficacy of 400/100 mg ibuprofen/caffeine, compared to 400 mg ibuprofen alone, for treating acute pain, reflecting that caffeine is an effective analgesic adjuvant. Data on efficacy of 400 mg ibuprofen combined with caffeine for the treatment of acute pain were not available yet.

Pharmacokinetic Properties of Ibuprofen (IBU) From the Fixed‐Dose Combination IBU/Caffeine (400/100 mg; FDC) in Comparison With 400 mg IBU as Acid or Lysinate Under Fasted and Fed Conditions—Data From 2 Single‐Center, Single‐Dose, Randomized Crossover Studies in Healthy Volunteers

“…In a recent clinical study, ibuprofen 400 mg plus caffeine 100 mg showed improved analgesic efficacy compared with 400 mg ibuprofen alone in subjects experiencing dental pain after their third molar extraction, whereby meaningful pain relief was reached 39 minutes earlier with the FDC. 4 In headache, ibuprofen combined with caffeine has been shown to be more efficacious compared with ibuprofen alone. 18 Thus, the improved PK properties of the FDC presented here can be assumed to add to the favorable pharmacodynamic properties of caffeine-containing analgesic preparations in different conditions of acute pain.…”

“…Caffeine is a well‐proven and widely used analgesic adjuvant, and fixed‐dose combination (FDC) products of caffeine with acetylsalicylic acid, paracetamol, or both analgesics are available in many countries. Recently, a clinical study investigating the efficacy, tolerability, and safety of the FDC IBU 400 mg plus caffeine 100 mg compared with its single ingredients and placebo for the treatment of acute pain was reported …”

“…Recently, a clinical study investigating the efficacy, tolerability, and safety of the FDC IBU 400 mg plus caffeine 100 mg compared with its single ingredients and placebo for the treatment of acute pain was reported. 4 Ibuprofen is an NSAID with potent analgesic and antipyretic effects. It reduces the production of prostaglandins associated with inflammation and pain by inhibiting the cyclooxygenase-1 and -2 enzymes.…”

Effect of preemptive analgesia with ibuprofen in the control of postoperative pain in dental implant surgeries: A randomized, triple-blind controlled clinical trial

“…In addition, different types of drugs have been tested in PA (1,9,(13)(14)(15)(16) however without a consensual definition of the best protocol regarding the drug, posology and period of exposure to the drug. Studies have shown a high preference for the use of Ibuprofen in pain control related to dental problems or dental procedures (12,16,19) Ibuprofen, a name derived from the initials of isobutylphenyl propionic acid, is a drug in the group of NSAIDs which acts by non-selectively inhibiting cyclooxygenase 1 and 2 thus avoiding the consequent formation of pro-inflammatory mediators by the arachidonic acid cascade (19). In this sense, the hypothesis for this study was that individuals who receive PA with the use of ibuprofen (600 mg, oral) 1 hour before the implant surgery present lower postoperative pain in relation to individuals receiving placebo medication.…”

A Randomized, Double-Blind, Placebo-Controlled Trial of Ibuprofen Lysinate in Comparison to Ibuprofen Acid for Acute Postoperative Dental Pain

“…A Cochrane meta-analysis confirmed that analgesics combined with caffeine provide more effective pain relief than analgesics without caffeine [22]. Moreover, a recent study on the efficacy and safety of the combination of 400 mg ibuprofen acid with 100 mg caffeine in the dental extraction model showed that this combination was more efficacious and had a faster onset of action than ibuprofen acid alone [23]. Thus, combining ibuprofen with caffeine or another analgesic agent appears to be a more efficient way to increase its analgesic activity than administering ibuprofen as a lysine salt formulation.…”