Local Infiltration Analgesia With and Without EXPAREL Following Total Knee Arthroplasty

Inclusion Criteria: 1. Male or female, at least 18 years of age at screening. 2. Scheduled to undergo primary, unilateral, tricompartmental TKA under spinal anesthesia. 3. Primary indication for TKA is degenerative osteoarthritis of the knee. 4. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3. 5. Female subjects must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the FDA for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study. 6. Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments. Exclusion Criteria: 1. Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration. 2. History of previous prior contralateral TKA or open knee surgery on the knee being considered for TKA. Prior arthroscopy is permitted. 3. Planned concurrent surgical procedure (e.g., bilateral TKA). 4. Undergoing unicompartmental TKA or revision TKA. 5. Concurrent painful physical condition that may require analgesic treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not strictly related to the knee surgery and which may confound the postsurgical assessments (e.g., significant pain from other joints including the non-index knee joint, chronic neuropathic pain, concurrent or prior contralateral TKA, concurrent foot surgery). 6. Comorbidity impacting current physical function of Investigator opinion that it may impact postsurgical rehabilitation. 7. Allergy, hypersensitivity, or contraindication to any of the study medications (i.e., bupivacaine, pregabalin, acetaminophen/paracetamol, celecoxib, oxycodone, morphine, hydromorphone, or tranexamic acid). 8. Use of any of the following medications within the times specified before surgery: long-acting opioid medication or NSAIDs (except for low-dose aspirin used for cardioprotection) within 3 days, or any opioid medication within 24 hours. 9. Initiation of treatment with any of the following medications within 1 month of study drug administration or if the medication(s) are being given to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®). If a subject is taking one of these medications for a reason other than pain control, he or she must be on a stable dose for at least 1 month prior to study drug administration. 10. Current use of systemic glucocorticosteroids within 1 month of enrollment in this study. 11. Use of dexmedetomidine HCl (Precedex®) within 3 days of study drug administration. 12. History of coronary or vascular stent placed within the past 3 months (may be extended to 1 year if medically indicated per physician discretion). 13. Have been treated for a deep vein thrombosis, pulmonary embolism, myocardial infarction, or ischemic stroke within the past 6 months (may be extended to 1 year if medically indicated per physician discretion). 14. Rheumatoid or inflammatory arthritis or disease. 15. Severely impaired renal or hepatic function (e.g., serum creatinine level \>2 mg/dL \[176.8 µmol/L\], blood urea nitrogen level \>50 mg/dL \[17.9 mmol/L\], serum aspartate aminotransferase \[AST\] level \>3 times the upper limit of normal \[ULN\], or serum alanine aminotransferase \[ALT\] level \>3 times the ULN.) 16. Any neurologic or psychiatric disorder that might impact postsurgical pain or interfere with study assessments. 17. Malignancy in the last 2 years, per physician discretion. 18. History of misuse, abuse, or dependence on opioid analgesics, other prescription drugs, illicit drugs, or alcohol. 19. Failure to pass the alcohol breath test or urine drug screen. 20. Body weight \<50 kg (110 pounds) or a body mass index \>40 kg/m2. 21. Previous participation in an EXPAREL study. 22. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.