|Phase 4 Study Shows EXPAREL® Versus an Active Comparator Significantly Reduces Opioid Consumption and Postsurgical Pain in Patients Undergoing Total Knee Arthroplasty|
Multicenter randomized study serves as unequivocal evidence of EXPAREL as an opioid minimizing agent in a complex and painful surgical procedure
Protocol’s best practice infiltration technique for the use of EXPAREL will be focus of educational programs at
The co-primary efficacy endpoints were the area under the curve (AUC) of the pain intensity scores measured on a visual analog scale (VAS) from 12 to 48 hours after surgery and the total opioid consumption expressed as morphine equivalents from zero to 48 hours after surgery. The EXPAREL group achieved a statistically significant reduction in pain scores compared to the group who did not receive EXPAREL (p=0.0381). Additionally, patients who received EXPAREL consumed significantly fewer opioids than patients who did not receive EXPAREL during the 48 hours that followed surgery (p=0.0048).
Sixteen centers participated in this trial with 139 patients randomized to an EXPAREL-based or a bupivacaine-based multimodal pain regimen of oral acetaminophen, celecoxib and pregabalin. In addition, all patients received intravenous tranexamic acid at the beginning of surgery or intra-operatively.
The study showed the EXPAREL group achieved statistically significant differences compared to the group who did not receive EXPAREL for the following key secondary endpoints:
“The operating room is the gateway to opioid abuse and places patients at serious risk for addiction and dependence,” said
This Phase 4 study was a multicenter, randomized, double-blind, controlled, parallel group study. Patients were randomized to receive local infiltration analgesia with 266 mg of EXPAREL admixed with bupivacaine and expanded in volume to 120 mL (20 mL EXPAREL vial admixed with 20 mL standard bupivacaine 0.5% and expanded with 80 mL normal saline) to local infiltration analgesia with bupivacaine expanded in volume to 120 mL (20 mL standard bupivacaine 0.5% and expanded with 100 mL normal saline). Investigators administered study drug using six 20 mL prefilled syringes.
To support optimal and replicable outcomes in TKA, this study used a standardized infiltration protocol designed by experienced clinicians to define best practice technique for administering EXPAREL. Key features of the infiltration protocol include volume expansion to ensure full coverage of the nerve fibers responsible for sending pain signals to the brain, admixing with free bupivacaine to provide sufficient immediate pain relief, and a clear definition of the sites for infiltration and administration technique to ensure adequate coverage of the impacted nerve fibers.
Pacira and its partner,
EXPAREL (bupivacaine liposome injectable suspension) is currently indicated for single-dose infiltration into the surgical site to produce postsurgical analgesia. The product combines bupivacaine with DepoFoam®, a proven product delivery technology that delivers medication over a desired period of time. EXPAREL represents the first and only multivesicular liposome local anesthetic that can be utilized in the peri- or postsurgical setting. By utilizing the DepoFoam platform, a single dose of EXPAREL delivers bupivacaine over time, providing significant reductions in cumulative pain score with up to a 45 percent decrease in opioid consumption; the clinical benefit of the opioid reduction was not demonstrated. Additional information is available at http://www.exparel.com/hcp/pdf/EXPAREL_Prescribing_Information.pdf.
Important Safety Information
EXPAREL is contraindicated in obstetrical paracervical block anesthesia. EXPAREL has not been studied for use in patients younger than 18 years of age. Non-bupivacaine-based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. Other formulations of bupivacaine should not be administered within 96 hours following administration of EXPAREL. Monitoring of cardiovascular and neurological status, as well as vital signs should be performed during and after injection of EXPAREL as with other local anesthetic products. Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations. In clinical trials, the most common adverse reactions (incidence greater-than or equal to 10%) following EXPAREL administration were nausea, constipation, and vomiting.
Please see the full Prescribing Information for more details available at: http://www.exparel.com/hcp/pdf/EXPAREL_Prescribing_Information.pdf.
Forward Looking Statements
Any statements in this press release about our future expectations, plans, outlook and prospects, and other statements containing the words “believes,” “anticipates,” “plans,” “estimates,” “expects,” “intends,” “may” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks relating to: the success of our sales and manufacturing efforts in support of the commercialization of EXPAREL; the rate and degree of market acceptance of EXPAREL and our other products; the size and growth of the potential markets for EXPAREL and our ability to serve those markets; our plans to expand the use of EXPAREL to additional indications and opportunities, and the timing and success of any related clinical trials; the related timing and success of
1. “Volleyball Legend Gabrielle Reece on Knee Replacement, Managing Pain, Olympics and More.” USA Today,