Bupivacaine/meloxicam ER: A New Dual-acting Extended-Release Local Anesthetic for Opioid-Sparing Postoperative Pain Management.

OBJECTIVE: To review data for bupivacaine/meloxicam extended-release (ER) solution for management of postoperative pain and opioid-sparing effects. DATA SOURCES: Literature search of PubMed (1946 to August 2021) and ProQuest (1946 to August 2021) was performed using the terms: Zynrelef, HTX-011, and "bupivacaine AND meloxicam." Additional information sources include ClinicalTrials.gov, prescribing information, Heron Therapeutics' Clinical and Economic Evidence Dossier, meeting abstracts, and references of identified articles. STUDY SELECTION AND DATA EXTRACTION: Clinical trials and articles evaluating bupivacaine/meloxicam ER for postoperative pain management. DATA SYNTHESIS: Bupivacaine is a short-acting local anesthetic. Its efficacy is negatively impacted by the acidic environment of surgical sites. Meloxicam, a nonsteroidal antiinflammatory, reduces inflammation at the surgical site and increases pH propagating bupivacaine movement into the neurons. In Phase 2 and Phase 3 clinical trials, bupivacaine/meloxicam ER was compared with bupivacaine HCl, bupivacaine ER, and meloxicam ER with and without scheduled nonopioid multimodal analgesia (MMA) in bunionectomies, herniorrhaphies, total knee arthroplasty and abdominoplasty. Postoperative pain was well controlled for 72 hours and consistently superior to placebo, with minimal or no opioid use. Wound healing was not impacted and adverse effects were similar to placebo (most commonly nausea, dizziness, constipation, and headaches). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Bupivacaine/meloxicam ER is a viable, safe, nonopioid local anesthetic for sustained 72-hour postoperative pain management mitigating opioid consumption. CONCLUSION: Bupivacaine/meloxicam ER is the only dual-acting, extended-release local anesthetic available. It provides effective analgesia in the postoperative setting and successfully reduces or eliminates postoperative opioid consumption.

Difelikefalin: A New κ-Opioid Receptor Agonist for the Treatment of Hemodialysis-Dependent Chronic Kidney Disease-Associated Pruritus.

OBJECTIVE: To review data for difelikefalin (Korsuva) intravenous solution for management of moderate-to-severe pruritus in hemodialysis (HD) patients. DATA SOURCES: Literature search of PubMed (January 1946-May 2022) and SCOPUS (January 1946-May 2022) was performed using the terms: Korsuva, CR845, and difelikefalin. Additional information sources include ClinicalTrials.gov, prescribing information, meeting posters, and references of identified articles. STUDY SELECTION AND DATA EXTRACTION: Clinical trials and articles evaluating difelikefalin for chronic kidney disease-associated pruritis (CKD-aP) in HD patients. DATA SYNTHESIS: Difelikefalin is a peripherally acting κ-opioid receptor agonist with antipruritic effects for HD patients with moderate-to-severe CKD-aP. A phase 3 study showed significant improvement of patient itch intensity and itch-related quality of life (QOL) when compared with placebo. More patients had decreased pruritus on the 24-hour Worst Itch Intensity Numerical Rating Scale with difelikefalin (49.1%) compared with placebo (27.9%, P < 0.001). A positive effect was seen with or without use of additional antipruritic agents. Common adverse events include diarrhea, dizziness, and vomiting; there were no signs of physical dependence or centrally acting opioid effects (euphoria, hallucinations). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Difelikefalin reduced itch intensity and improved QOL for patients with CKD-aP. Whether the benefit is continued long-term as well as how it compares with other effective agents is currently unknown. CONCLUSION: Difelikefalin is the only Food and Drug Administration-approved treatment for moderate-to-severe CKD-aP with additional research into its benefit in this and other types of pruritus ongoing.