Oliceridine, a parenterally administered μ-receptor opioid agonist, is approved for the management of moderate to severe acute pain in adults requiring an intravenous (IV) opioid and for whom alternative treatments are inadequate. The treatment is indicated for short-term use in hospitals or other controlled clinical settings, not at-home use. Oliceridine has a maximum recommended daily dose of 27 mg.
The drug’s safety and efficacy were established in two randomized, double-blind, placebo- and morphine-controlled studies of 790 adult patients with moderate to severe acute pain after orthopedic or abdominal surgery. In both trials, patients were randomized to 1 of 3 dosing regimens, or to a placebo- or a morphine-control regimen. After a loading dose of 1.5 mg, oliceridine was administered via patient-controlled analgesia (PCA) at doses of 0.1, 0.35, or 0.5 mg depending on the assigned treatment group. Supplemental doses of 0.75 mg were administered as needed.
Patients receiving PCA doses of oliceridine 0.35 and 0.5 mg reported significantly lower pain levels (measured as greater summed pain intensity difference) than the placebo cohort.
The most common adverse events (AEs; occurring in ≥10% of patients) were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia. Discontinuation due to AEs occurred in 4% of patients who received a daily dose ≤27 mg and less than 1% of patients who received a daily dose >27 mg.
The sponsor also conducted an open-label study of 768 patients with moderate to severe acute pain following surgical procedures or due to a medical condition, including patients who were older, were obese, or had comorbid conditions such as diabetes or sleep apnea. A total of 55% of patients received treatment via clinician-administered bolus dosing, and 45% via PCA or a combination of the two methods. Bolus dosing was initiated at 1 to 2 mg, with supplemental doses of 1 to 3 mg every 1 to 3 hours, as needed. For PCA administration, the loading dose was 1.5 mg and the demand dose was 0.5 mg. Supplemental doses of 1 mg were given as needed. In this group, discontinuation due to AEs occurred in 3% of patients who received a daily dose ≤27 mg and 1% of patients who received a daily dose >27 mg.
The safety profile of oliceridine is similar to other opioids, and the treatment label includes a boxed warning about addiction and misuse, life-threatening respiratory depression, neonatal opioid withdrawal syndrome, and risks from concomitant use with benzodiazepines or other central nervous system depressants.
In October 2018, an advisory committee of the FDA voted 8-7 against the approval of oliceridine, due to concerns that the benefits of the drug did not exceed the risks, which included QTc prolongation. The FDA rejected the oliceridine application in November 2018 and then withdrew breakthrough status in 2019, but it later agreed to reconsider the drug after the sponsor performed additional safety studies and lowered the maximum daily recommended dose.