Titre du document / Document title

Analgesic efficacy and tolerability of oxycodone 5 mg/ ibuprofen 400 mg compared with those of oxycodone 5 mg/ acetaminophen 325 mg and hydrocodone 7.5 mg/ acetaminophen 500 mg in patients with moderate to severe postoperative pain : A randomized, double-blind, placebo-controlled, single-dose, parallel-group study in a dental pain model

Auteur(s) / Author(s)

LITKOWSKI Leonard J. ⁽¹⁾ ; CHRISTENSEN Steven E. ⁽²⁾ ; ADAMSON Dennis N. ⁽²⁾ ; VAN DYKE Thomas ⁽³⁾ ; HAN Seung-Ho ⁽⁴⁾ ; NEWMAN Kenneth B. ⁽⁴⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Center for Clinical Studies, Dental School, University of Maryland, Baltimore, Maryland, ETATS-UNIS
⁽²⁾ Jean Brown Research Recovery Center, Salt Lake City, Utah, ETATS-UNIS
⁽³⁾ Goldman School of Dental Medicine, Boston University, Boston, Massachusetts, ETATS-UNIS
⁽⁴⁾ Forest Research Institute, Jersey City, New Jersey, ETATS-UNIS

Résumé / Abstract

Background: Combination therapy has been widely used for the clinical management of acute pain. By combining 2 drugs with different mechanisms of action, such therapy provides additive analgesic effects while reducing the risk for adverse effects. Objective: This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo in a dental pain model. Methods: This was a multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group, single-dose study in patients experiencing moderate to severe pain after surgical removal of ≥2 ipsilateral impacted third molars. Patients were randomly assigned to receive oxycodone 5 mg/ibuprofen 400 mg, oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, or placebo. The primary outcome measures were total pain relief through 6 hours after dosing (TOTPAR₆), sum of pain intensity differences through 6 hours (SPID₆), and adverse events. Secondary efficacy measures included SPID₃ and TOTPAR₃, peak pain relief, peak pain intensity difference, time to onset of pain relief, time to use of rescue medication, proportion of patients reporting pain half gone, and the patient's global evaluation. Results: Two hundred forty-nine patients (43.5% male; 87.5% white; mean age, 19.1 years; mean body weight, 153.6 pounds) were randomized to treatment as follows: 62 to oxycodone 5 mg/ibuprofen 400 mg, 61 to oxycodone 5 mg/acetaminophen 325 mg, 63 to hydrocodone 7.5 mg/acetaminophen 500 mg, and 63 to placebo. Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo (mean [SD] TOTPAR₆, 14.98 [5.37], 9.53 [6.77], 8.36 [6.68], and 5.05 [6.49], respectively; P < 0.001, oxycodone 5 mg/ ibuprofen 400 mg vs all other treatments). SPID₆ values also differed significantly for oxycodone 5 mg/ ibuprofen 400 mg compared with all other treatments (mean: 7.78 [4.11], 3.58 [4.64], 3.32 [4.73], and 0.69 [4.85]; P < 0.001). Oxycodone 5 mg/ibuprofen 400 mg was significantly more effective compared with the other treatments on all secondary end points (P < 0.001, all variables except peak PID vs oxycodone 5 mg/acetaminophen 325 mg [P = 0.006]), with the exception of the time to onset of analgesia. The lowest frequency of nausea and vomiting occurred in the groups that received oxycodone 5 mg/ibuprofen 400 mg (6.5% and 3.2%, respectively) and placebo (3.2% and 1.6%). Rates of nausea and vomiting were significantly lower with oxycodone 5 mg/ibuprofen 400 mg compared with oxycodone 5 mg/acetaminophen 325 mg (P = 0.011 and P = 0.009, respectively) but not with hydrocodone 7.5 mg/acetaminophen 500 mg. Conclusions: In this study in patients with moderate to severe pain after surgery to remove impacted third molars, oxycodone 5 mg/ibuprofen 400 mg provided significantly better analgesia throughout the 6-hour study compared with the other opioid/ nonopioid combinations tested, and was associated with fewer adverse events.

Revue / Journal Title

Clinical therapeutics   ISSN 0149-2918 

Source / Source

2005, vol. 27, n^o4, pp. 418-429 [12 page(s) (article)] (31 ref.)

Langue / Language

Anglais

Editeur / Publisher

Excerpta Medica, Belle Mead, NJ, ETATS-UNIS  (1977) (Revue)

Mots-clés anglais / English Keywords

Enzyme ; Oxidoreductases ; Prostaglandin-endoperoxide synthase ; Enzyme inhibitor ; Arylpropionic acid derivatives ; Antitussive agent ; Antimigrainous agent ; Antipyretic ; Narcotic analgesic ; Non steroidal antiinflammatory agent ; Opioid peptide ; Opiates ; Analgesia ; Models ; Tooth ; Single dose ; Double blind study ; Randomization ; Pain ; Postoperative ; Human ; Hydrocodone ; Paracetamol ; Ibuprofen ; Oxycodone ; Toxicity ;

Mots-clés français / French Keywords

Enzyme ; Oxidoreductases ; Prostaglandin-endoperoxide synthase ; Inhibiteur enzyme ; Arylpropionique acide dérivé ; Antitussif ; Antimigraineux ; Antipyrétique ; Analgésique narcotique ; Antiinflammatoire non stéroïde ; Peptide opioïde ; Opiacés ; Analgésie ; Modèle ; Dent ; Dose unique ; Etude double insu ; Randomisation ; Douleur ; Postopératoire ; Homme ; Hydrocodone ; Paracétamol ; Ibuprofène ; Oxycodone ; Toxicité ;

Mots-clés espagnols / Spanish Keywords

Enzima ; Oxidoreductases ; Prostaglandin-endoperoxide synthase ; Inhibidor enzima ; Arilpropionico ácido derivado ; Antitusivo ; Agente antimigrañoso ; Antipirético ; Analgésico narcotico ; Antiinflamatorio no esteroide ; Péptido opioide ; Opiados ; Analgesia ; Modelo ; Diente ; Dosis única ; Estudio doble ciego ; Aleatorización ; Dolor ; Postoperatorio ; Hombre ; Hidrocodona ; Paracetamol ; Ibuprofeno ; Oxicodona ; Toxicidad ;

Mots-clés d'auteur / Author Keywords

analgesia ; dental pain ; opioid ; NSAID ; oxycodone ; ibuprofen ; hydrocodone ; acetaminophen ;

Localisation / Location

INIST-CNRS, Cote INIST : 18353, 35400012458627.0050