Three Newly Approved Analgesics: An Update

Since 2008, three new analgesic entities, tapentadol immediate release (Nucynta) diclofenac potassium soft gelatin capsules (Zipsor), and bupivacaine liposome injectable suspension (EXPAREL) were granted US Food and Drug Administration (FDA) approval to treat acute pain. Tapentadol immediate-release is a both a mu-opioid agonist and a norepinephrine reuptake inhibitor, and is indicated for the treatment of moderate to severe pain. Diclofenac potassium soft gelatin capsules are a novel formulation of diclofenac potassium, which is a nonsteroidal anti-inflammatory drug (NSAID), and its putative mechanism of action is through inhibition of cyclooxygenase enzymes. This novel formulation of diclofenac allows for improved absorption at lower doses. Liposomal bupivacaine is a new formulation of bupivacaine intended for single-dose infiltration at the surgical site for postoperative analgesia. Bupivacaine is slowly released from this liposomal vehicle and can provide prolonged analgesia at the surgical site. By utilizing NSAIDs and local anesthetics to decrease the transmission of afferent pain signals, less opioid analgesics are needed to achieve analgesia. Since drug-related adverse events are frequently dose related, lower doses from different drug classes may be employed to reduce the incidence of adverse effects, while producing synergistic analgesia as part of a multimodal analgesic approach to acute pain.Key Words: Liposomal bupivacaine, Tapentadol, Diclofenac potassium soft gelatin capsules, AnalgesicsPain, as defined by the International Association for the Study of Pain, is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”¹ Although there is a subjective and perhaps emotional component to pain, acute pain is usually proportional to the degree of tissue damage.²Pain may serve a protective mechanism to the individual by signaling tissue injury or organ dysfunction that may otherwise result in illness if left unnoticed and untreated. However, pain that is secondary to a surgical intervention is undesirable. Postoperative pain can result in increased sympathetic nervous system activity, guarded breathing, increased likelihood of thrombi formation, and delayed recovery.³ The benefits of adequate postoperative analgesia include improved respiratory, cardiovascular, and gastrointestinal function, improved arterial graft survival, and decreased incidence of thrombotic or septic complications. Not only does adequate postoperative analgesia result in earlier return to function, more rapid patient mobilization, improved healing, reduced health care costs, and improved patient satisfaction, but it may play a role in preventing the progression of chronic pain.^4–6Opioids have traditionally been the most common analgesic for treating moderate to severe postoperative pain.² However, their utility is hampered by undesirable side effects, which are sometimes intolerable to the patient. These side effects include central nervous depression, respiratory depression, pruritus, nausea, vomiting, ileus, tolerance, and opioid-induced hyperalgesia.^4–6 By treating pain with several modalities, including local anesthetics and nonsteroidal anti-inflammatory drugs (NSAIDs,) lower doses of opioids are needed to achieve analgesia while reducing or eliminating opioid-mediated adverse effects.^4,5The multimodal approach to analgesia intervenes pharmacologically at many different inputs along the pain pathway. The synergistic analgesia achieved by affecting pain transmission at multiple points also results in lower doses of each drug administered. Adverse drug reactions or drug toxicities are dose-dependent, so there are fewer side effects from each drug class. This article presents and reviews 3 new analgesic agents that may be useful in treating postoperative dental and maxillofacial pain: tapentadol immediate release (Nucynta) diclofenac potassium soft gelatin capsules (Zipsor) and bupivacaine liposome injectable suspension (EXPAREL).