Efficacy and Safety of Low Dose Subcutaneous Diclofenac in the Management of Acute Pain: A Randomized Double-Blind Trial

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 75mg/3mL 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 1mL-volume formulation of diclofenac sodium (25, 50 or 75mg) containing hydroxypropyl-beta-cyclodextrin (HP beta CD) as a solubility enhancer. This low-volume formulation allows subcutaneous (SC), in addition to intramuscular (IM) administration. Patients developing moderate-to-severe pain (>= 50mm on Visual Analogue Scale) after third molar extraction under local anesthesia were randomized to one of the 4 SC injections: 25mg diclofenac HP beta CD (n=77), 50mg diclofenac HP beta CD (n=76), 75mg diclofenac HP beta CD (n=78), or placebo (n=75). Results Mean pain intensity difference at 1.5hours 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 25mg group, 37.3 (32.6 to 42.1) in diclofenac 50mg group, 37.7 (33.0 to 42.4) in diclofenac 75mg group, and 12.3 (7.44 to 17.1) in placebo group. Both 25 and 50mg doses of diclofenac produced significantly greater pain relief than placebo (P<0.001 in both comparisons). Conclusion Single SC doses of diclofenac HP beta CD of 25 and 50mg are effective and well tolerated for relieving pain compared with placebo.