title: Efficacy and safety of low dose subcutaneous diclofenac in the management of acute pain: a randomized double-blind trial.
abstract: OBJECTIVE
  Diclofenac is an effective and well-tolerated nonsteroidal anti-inflammatory drug (NSAID) frequently used in the treatment of acute pain. Marketed formulations for parenteral administration usually contain 75 mg/3 mL of diclofenac sodium, which provide limited dosing flexibility, and are usually given intramuscularly.
  
  
  METHODS
  We present a randomized, double-blind, active comparator- and placebo-controlled, parallel-group phase III multicenter study, investigating efficacy and tolerability of a new 1 mL-volume formulation of diclofenac sodium (25, 50 or 75 mg) containing hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer. This low-volume formulation allows subcutaneous (SC), in addition to intramuscular (IM) administration. Patients developing moderate-to-severe pain (≥ 50 mm on Visual Analogue Scale) after third molar extraction under local anesthesia were randomized to one of the 4 SC injections: 25 mg diclofenac HPβCD (n = 77), 50 mg diclofenac HPβCD (n = 76), 75 mg diclofenac HPβCD (n = 78), or placebo (n = 75).
  
  
  RESULTS
  Mean pain intensity difference at 1.5 hours postdose (primary endpoint) was higher in all diclofenac-treated groups than placebo group. The adjusted means (95% CI) were 36.5 (31.7 to 41.2) in diclofenac 25 mg group, 37.3 (32.6 to 42.1) in diclofenac 50 mg group, 37.7 (33.0 to 42.4) in diclofenac 75 mg group, and 12.3 (7.44 to 17.1) in placebo group. Both 25 and 50 mg doses of diclofenac produced significantly greater pain relief than placebo (P < 0.001 in both comparisons).
  
  
  CONCLUSIONS
  Single SC doses of diclofenac HPβCD of 25 and 50 mg are effective and well tolerated for relieving pain compared with placebo.
authors.affiliation: The School of Dentistry, University of Birmingham, Birmingham, U.K.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dietrich
authors.forename: Rachel
authors.initials: R
authors.lastname: Leeson
authors.forename: Barbara
authors.initials: B
authors.lastname: Gugliotta
authors.forename: Birte
authors.initials: B
authors.lastname: Petersen
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D059787:Acute Pain / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004008:Diclofenac / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005079:Excipients / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D018401:Sample Size; D064232:Visual Analog Scale; D055815:Young Adult; D047392:beta-Cyclodextrins / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D047392:beta-Cyclodextrins; D004008:Diclofenac; D000073738:2-Hydroxypropyl-beta-cyclodextrin
keywords: acute pain; randomized controlled trial; subcutaneous diclofenac