Oliceridine (Olinvyk) Offers New Treatment Option for Acute Pain Management in Hospitals and Controlled Clinical Settings

Oliceridine (Olinvyk; Trevena, Inc) is an intravenous (IV) opioid agonist indicated in adults for management of acute severe pain in a hospital or controlled clinical setting.^1,2

Oliceridine should only be used in patients who require an IV opioid analgesic and for whom alternative treatments are inadequate.¹ Oliceridine is a novel μ-opioid receptor ligand with reduced β-arrestin recruitment.³ β-Arrestin signaling is thought to contribute to opioid-related adverse events (AEs) seen with conventional opioids.³ Common opioid-related AEs include nausea, vomiting, constipation, and respiratory depression.⁴ Oliceridine is intended to be an opioid with an improved respiratory safety profile and reduced incidence of nausea and vomiting. Controlled substance schedule for oliceridine is pending.

Efficacy

The APOLLO-1 and APOLLO-2 trials evaluated the efficacy and safety of oliceridine for acute pain following bunionectomy and abdominoplasty, respectively.^3,4 In both trials, patients received a loading dose of either placebo, oliceridine (1.5 mg), or morphine (4 mg), followed by demand doses via patient-controlled analgesia (0.1, 0.35, or 0.5 mg oliceridine, 1 mg morphine, or placebo). The primary end point for both trials was the proportion of treatment responders to oliceridine compared with placebo. In APOLLO-1, oliceridine was shown to be an effective analgesic with responder rates of 50%, 62%, and 65.8% in the 0.1 mg, 0.35 mg, and 0.5 mg regimens, respectively, compared with 15.2% for placebo (all P < .0001).³ Oliceridine was also shown to be effective in APOLLO-2 with responder rates of 61%, 76.3%, and 70.0% for 0.1 mg, 0.35 mg, and 0.5 mg regimens, respectively, compared with 45.7% for placebo (all P < .05).⁴

In both trials, the composite measure of respiratory safety burden was not statistically different from morphine; however, APOLLO-1 patients in the 0.1-mg and 0.35-mg regimens had a significantly lower risk of experiencing a respiratory safety event when compared with morphine.³ Of the 3 oliceridine regimens, 0.35 mg and 0.5 mg were shown to be noninferior to morphine at achieving treatment response in both trials.^3,4

Safety

The most commonly reported AEs for oliceridine were nausea, vomiting, headache, and dizziness.¹ The proportion of patients experiencing 1 or more gastrointestinal-related AEs increased in a dose-dependent manner across the 3 oliceridine regimens.^3,4 In APOLLO-1, the proportion of gastrointestinal-related AEs ranged from 40.8% to 70.9% in the oliceridine regimens compared with 24.1% for placebo and 72.4% for morphine.³

Dosing and Administration

The recommended initial dose is 1.5 mg given IV.¹ Onset of analgesic effect is expected within 2 to 5 minutes after initial dose.¹ Supplemental doses of 0.75 mg can be administered 1 hour after the initial dose and as needed hourly thereafter.¹ For patient-controlled analgesia (PCA), the recommended demand dose is 0.35 mg, with a 6-minute lock out. The cumulative daily dose should not exceed 27 mg due to risk of QT prolongation. Oliceridine 1 mg is approximately equipotent to morphine 5 mg.¹ Oliceridine is available as single-dose 2 mL (1 mg/mL) vials and as 30 mg/30 mL (1mg/mL) vials for PCA use only.

Patients with decreased cytochrome P450 2D6 function, patients taking a moderate/strong cytochrome P450 3A4 (CYP3A4) inhibitor, or patients who have very recently discontinued a CYP3A4 inducer are at risk of increased plasma concentrations of oliceridine.¹

References 

1. Olinvyk. Prescribing information. Trevena Inc; 2020. Accessed August 31, 2020. https://olinvyk.com/docs/OLINVYK-FINAL-LABEL-07Aug2020.pdf​

2. FDA approves new opioid for Intravenous use in hospitals, other controlled clinical settings. News release. FDA. August 7, 2020. Accessed August 31, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-new-opioid-intravenous-use-hospitals-other-controlled-clinical-settings.

3. Viscusi ER, Skobieranda F, Soergel DG, Cook E, Burt DA, Singla N. 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. doi:10.2147/JPR.S171013​

4. 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;19(7):715-731. doi:10.1111/papr.12801