Phase 4 Study Demonstrates Superiority of EXPAREL plus Bupivacaine versus Bupivacaine Alone in Cesarean Section Procedures
– TAP block with EXPAREL provides significant reductions in opioids and pain scores –
– Results presented at
This was a multicenter, randomized, double-blind study across 13 clinical sites in
- Significant reduction in total opioid consumption with EXPAREL plus bupivacaine HCl versus bupivacaine HCl
- 52% reduction through 72 hours, the primary endpoint of the study (least squares mean [LSM] standard error [SE], 15.5 [6.67] vs 32.0 [6.25] mg, respectively; P=0.0117)
- 49% reduction at one week (LSM [SE], 23.3 [9.75] vs 45.8 [9.13] mg, respectively; P=0.0175)
- 41% reduction at two weeks (LSM [SE], 28.2 [11.20] vs 47.8 [10.49] mg, respectively; P=0.0542)
- Significantly lower cumulative pain scores through 72 hours with EXPAREL versus bupivacaine HCl, measured using the area under the curve of imputed pain intensity scores collected from 6 to 72 hours (LSM [SE], 147.9 [21.13] vs 178.5 [19.78], respectively; P=0.002)
- Significantly higher percentage of opioid-spared patients with EXPAREL versus bupivacaine HCl, defined as patients who took no more than one oxycodone 10 mg tablet (or equivalent) with no opioid-related side effects through 72 hours
- Percentage of opioid-spared patients was 2.2 times higher in the EXPAREL group vs bupivacaine HCl group (54% vs 25%, respectively; P=0.0012)
“Inadequately managed postsurgical pain following cesarean delivery can increase the risks of persistent pain and opioid use, as well as postpartum depression,” said
Safety was comparable between groups in this study, with 64 percent of patients in the EXPAREL group experiencing a treatment-emergent adverse event (TEAE) versus 56 percent of patients in the bupivacaine HCl group. The most common TEAEs were pruritus (itching) and nausea; serious TEAEs were rare (approximately three percent in both groups). There were no fatal TEAEs.
Patients in the EXPAREL arm of this study were administered a TAP field block with 10 mL EXPAREL admixed with 10 mL 0.25% bupivacaine HCl and 10 mL normal sterile saline injected bilaterally (for a total volume of 60 mL). Patients in the active comparator arm received a TAP field block with 10 mL 0.25% bupivacaine HCl admixed with 20 mL normal sterile saline injected bilaterally (for a total volume of 60 mL).
In accordance with current medical practice, prior to C-section all patients in this study received an intrathecal injection of 150 mcg preservative-free morphine for spinal injection in conjunction with single-shot spinal anesthesia using 1.4-1.6 mL bupivacaine HCl 0.75% and 15 mcg fentanyl. Following C-section, patients also received 15 mg of intravenous (IV) ketorolac, 1000 mg of IV acetaminophen at the time of skin incision closure, and oral acetaminophen and ibuprofen beginning 6 hours after skin incision closure for up to 72 hours following surgery. Rescue medication was available upon request and postsurgical opioid consumption through 72 hours was collected.
Pacira is currently enrolling in CHOICE, its next-generation C-section trial designed to be completely opioid-free in the EXPAREL arm, including opioid-free spinal anesthesia.
“Research shows that up to fourteen percent of patients prescribed opioids to manage postsurgical pain suffer from opioid-related adverse events1 that can delay recovery and slow the healing process. These side effects can be particularly challenging for C-section patients who are balancing both recovering from surgery and caring for a newborn child,” said
EXPAREL (bupivacaine liposome injectable suspension) is indicated for single-dose infiltration in adults to produce postsurgical local analgesia and as an interscalene brachial plexus nerve block to produce postsurgical regional analgesia. Safety and efficacy have not been established in other nerve blocks. The product combines bupivacaine with DepoFoam®, a proven product delivery technology that delivers medication over a desired time period. 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 scores with up to a 78 percent decrease in opioid consumption; the clinical benefit of the opioid reduction was not demonstrated. Additional information is available at www.EXPAREL.com.
Important Safety Information
EXPAREL is contraindicated in obstetrical paracervical block anesthesia. Adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via infiltration were nausea, constipation, and vomiting; adverse reactions reported with an incidence greater than or equal to 10% following EXPAREL administration via interscalene brachial plexus nerve block were nausea, pyrexia, and constipation. If EXPAREL and other non-bupivacaine local anesthetics, including lidocaine, are administered at the same site, there may be an immediate release of bupivacaine from EXPAREL. Therefore, EXPAREL may be administered to the same site 20 minutes after injecting lidocaine. EXPAREL is not recommended to be used in the following patient population: patients <18 years old and/or pregnant patients. Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease. Warnings and Precautions Specific to EXPAREL: Avoid additional use of local anesthetics within 96 hours following administration of EXPAREL. EXPAREL is not recommended for the following types or routes of administration: epidural, intrathecal, regional nerve blocks other than interscalene brachial plexus nerve block, or intravascular or intra-articular use. The potential sensory and/or motor loss with EXPAREL is temporary and varies in degree and duration depending on the site of injection and dosage administered and may last for up to 5 days, as seen in clinical trials. Warnings and Precautions for Bupivacaine-Containing Products: Central Nervous System (CNS) Reactions: There have been reports of adverse neurologic reactions with the use of local anesthetics. These include persistent anesthesia and paresthesia. CNS reactions are characterized by excitation and/or depression. Cardiovascular System Reactions: Toxic blood concentrations depress cardiac conductivity and excitability which may lead to dysrhythmias, sometimes leading to death. Allergic Reactions: Allergic-type reactions (eg, anaphylaxis and angioedema) are rare and may occur as a result of hypersensitivity to the local anesthetic or to other formulation ingredients. Chondrolysis: There have been reports of chondrolysis (mostly in the shoulder joint) following intra-articular infusion of local anesthetics, which is an unapproved use. Methemoglobinemia: Cases of methemoglobinemia have been reported with local anesthetic use. Full Prescribing Information is available at www.EXPAREL.com.
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1 Kessler ER, Shah M, Gruschkus SK, Raju A. Pharmacotherapy.2013;33(4):383–391.