General Information

Exparel is a long-acting, sustained-release formulation of bupivacaine HCL, a local anesthetic widely used for treating postoperative pain. Exparel was formulated using the DepoFoam lipid-based delivery system. DepoFoam technology encapsulates the drug in multivesicular liposomal particles which then release the drug over a desired period of time without altering the drug molecule.

Exparel is specifically indicated:

• In patients 6 years of age and older for single-dose infiltration to produce postsurgical local analgesia
• In adults as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia

Exparel is supplied as a solution for injection. Exparel is intended for single-dose administration only. The recommended dose of Exparel is based on the surgical site and the volume required to cover the area. Exparel has only been evaluated in bunionectomy and hemorrhoidectomy procedures. It has not been demonstrated to be safe and effective in other procedures. The recommended dose of Exparel for bunionectomy is 106 mg or a volume of 8 mL. The recommended dose of Exparel for hemorrhoidectomy is 266 mg or a volume of 20 mL.

Mechanism of Action

Exparel is a long-acting, sustained-release formulation of bupivacaine HCL, a local anesthetic. Bupivacaine is related chemically and pharmacologically to the amide-type local anesthetics. Local anesthetics block the generation and the conduction of nerve impulses presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential.Exparel was formulated using the DepoFoam lipid-based delivery system. DepoFoam technology encapsulates the drug in multivesicular liposomal particles which then release the drug over a desired period of time without altering the drug molecule.

Side Effects

Adverse events associated with the use of Exparel may include, but are not limited to, the following:

• nausea
• constipation
• vomiting

Clinical Trial Results

The FDA approval of Exparel was based on two multicenter, randomized, double-blind clinical trials. One trial evaluated the treatments in subjects undergoing bunionectomy; the other trial evaluated the treatments in subjects undergoing hemorrhoidectomy.

Bunionectomy
This trial enrolled 193 subjects who received 106 mg of Exparel administered directly into the wound at the conclusion of the surgery, prior to wound closure. Pain intensity was rated by the subjects on a 0 to 10 numeric rating scale (NRS) out to 72 hours. The primary outcome measure was the area under the curve (AUC) of the NRS pain intensity scores (cumulative pain scores) collected over the first 24 hour period. Exparel demonstrated a significant reduction versus placebo only in the first 24 hours. Between 24 and 72 hours after study drug administration, there was minimal to no difference between Exparel and placebo treatments on mean pain intensity.

Hemorrhoidectomy
This trial enroll 189 subjects who received 266 mg of Exparel administered directly into the wound (greater than or equal to 3 cm) at the conclusion of the surgery. Pain intensity was rated by the subjects on a 0 to 10 NRS at multiple time points up to 72 hours. The primary outcome measure was the AUC of the NRS pain intensity scores (cumulative pain scores) collected over the first 72 hour period. Exparel demonstrated a significant reduction in pain intensity compared to placebo for up to 24 hours. The difference in mean pain intensity between treatment groups occurred only during the first 24 hours following study drug administration. Between 24 and 72 hours after study drug administration, there was minimal to no difference between Exparel and placebo treatments on mean pain intensity.