By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The Food and Drug Administration (FDA) has approved a novel opioid agonist for pain management. Oliceridine is a mu-opioid receptor (MOR) agonist similar to morphine. It is classified as a G-protein-biased ligand, possibly providing analgesic benefit while limiting adverse effects. It is given intravenously in a hospital or other controlled setting. The FDA initially rejected the drug in 2018 over safety concerns. The agency reconsidered and approved it in August 2020. Oliceridine is distributed as Olinvyk.


Oliceridine should be prescribed to adults to manage acute pain severe enough to require intravenous opioid analgesic and for whom alternative treatment has not worked.1


The initial recommended dose is 1.5 mg.1 For patient-controlled analgesia (PCA), the recommended dose is 0.35 mg with a six-minute lock-out. A demand dose of 0.5 mg may be considered. A supplemental dose of 0.75 mg can be given one hour after the initial dose and hourly thereafter, as needed. The cumulative daily dose should not exceed 27 mg. The lowest effective dose and shortest duration should be used and individualized based on pain severity, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse.1 Oliceridine is available as 1 mg/mL and 2 mg/2 mL single-dose vials and 30 mg/30 mL patient-single-use vials for PCA.


Oliceridine provides an alternative to opioids for managing moderate to severe pain. It may carry a slightly more favorable risk-benefit ratio because of difference in MOR binding/activation selectivity.2,3


Oliceridine is available in injectable form only. It shares the same warning as opioids, such as addiction, abuse, misuse, respiratory depression, neonatal opioid withdrawal syndrome, and interaction with benzodiazepine and other central nervous system depressants.1


Biased agonism is the ability of a molecule to activate different signaling pathways when binding to a receptor, in this case MOR.2,3 Analgesic effects and adverse effects are believed to be caused by activation of different signaling pathways (i.e., G-protein and beta-arrestin-2). Oliceridine shows preferential selectivity for the G-protein pathway in animal models.2 Conventional opioids are nonselective.

The approval of oliceridine was based on two randomized, placebo- and active-controlled, Phase III studies for moderate to severe pain following orthopedic surgery (bunionectomy; n = 389 in study 1) and plastic surgery (abdominoplasty; n = 401 in study 2).1,4,5 Most participants were women (85% in study 1 and 100% in study 2). In each study, subjects were randomized to oliceridine (1.5 mg loading followed by a demand dose of 0.1 mg, 0.35 mg, or 0.5 mg), morphine (4 mg loading dose, demand dose 1 mg), or volume-matched placebo. A lockout interval of six minutes was used for all PCA regimens. Clinician-administered supplemental doses of 0.75 mg oliceridine, 2 mg morphine, or volume-matched placebo were permitted. Rescue medication was administered as needed (etodolac 200 mg every six hours).

The primary efficacy endpoint was sum of pain intensity difference (SPID) from baseline at 48 hours (bunionectomy; SPID-48) or 24 hours (abdominoplasty; SPID-24). Responders were defined as: ≥ 30% SPID improvement, no rescue medicine, no early discontinuation, or did not reach protocol-specified dosing limit.

In study 1, FDA-approved dose of oliceridine (0.35 mg and 0.5 mg) and morphine were significantly more effective than placebo. Morphine was numerically (but not statistically) better. Response rates were 62%, 65.8%, and 71%, respectively, and 15.2% for placebo.4 Results were similar for study 2, with response rates of 76.3%, 70.0%, and 78.3%, respectively, vs. 45.7% for placebo.

Overall, the adverse reaction profiles were similar between oliceridine and morphine. There were some subtle differences. The odds ratio for rescue antiemetic use was significantly smaller with oliceridine vs. morphine in study 1 and numerically smaller in study 2.4,5 The percentage of patients who required oxygen supplementation was numerically lower in the oliceridine groups but did not reach statistical significance.4,5

In a Phase III, open-label study, 768 subjects (91% completion rate) with moderate to severe acute pain from mainly surgical procedures (orthopedic, colorectal, and gynecological) were evaluated for safety and effectiveness. Thirty-two percent of subjects were ≥ age 65 years, and 46% recorded a body mass index ≥ 30 kg/m2.6 Oliceridine appears to be generally well-tolerated and effective. Adverse reactions generally were mild (37%) or moderate (25%), with 2.2% discontinuing early because of adverse events. Nausea was the most common adverse reaction (31%). Changes in pain scores were reported within 30 minutes after the first dose. Discontinuation because of a lack of effectiveness was 4.3%.


Oliceridine is a novel MOR ligand. Although the preferential selectivity was therapeutically enticing, oliceridine does not appear to translate into any clear clinical advantage relative to improving the therapeutic index or widening the therapeutic window. Oliceridine should be reserved for patients when alternative options are not adequate or not tolerated. Drug Enforcement Agency scheduling is pending. Cost was unavailable at the time of this review.


  1. Trevena. Trevena announces FDA approval of Olinvyk (oliceridine) injection. Aug. 10, 2020.
  2. Urits I, Viswanath O, Orhurhu V, et al. The utilization of mu-opioid receptor biased agonists: Oliceridine, an opioid analgesic with reduced adverse effects. Curr Pain Headache Rep 2019;23:31.
  3. Stötzner P, Spahn V, Celik MÖ, et al. Mu-opioid receptor agonist induces kir3 currents in mouse peripheral sensory neurons - Effects of nerve injury. Front Pharmacol 2018;9:1478.
  4. Viscusi ER, Skobieranda F, Soergel DG, et al. APOLLO-1: A randomized placebo and active-controlled phase III study investigating oliceridine (TRV130), a G protein-biased ligand at the µ-opioid receptor, for management of moderate-to-severe acute pain following bunionectomy. J Pain Res 2019;12:927-943.
  5. Singla NK, Skobieranda F, Soergel DG, et al. APOLLO-2: A randomized, placebo and active-controlled phase III study investigating oliceridine (TRV130), a G protein-biased ligand at the μ-opioid receptor, for management of moderate to severe acute pain following abdominoplasty. Pain Pract 2019;7:715-731.
  6. Bergese SD, Brzezinski M, Hammer GB, et al. ATHENA: A phase 3, open-label study of the safety and effectiveness of oliceridine (TRV130), a G-protein selective agonist at the µ-opioid receptor, in patients with moderate to severe acute pain requiring parenteral opioid therapy. J Pain Res 2019;12:3113-3126.