FDA Approves Oliceridine for Management of Acute Pain

Oliceridine, an 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 requires no dosage adjustments in patients with renal impairment

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 one of three dosing regimens, or to either a placebo- or a morphine-control regimen. After a loading dose of 1.5 mg, oliceridine was administered intravenously via patient-controlled analgesia (PCA) at doses of 0.1, 0.35, or 0.5 mg depending on the assigned treatment group. Supplemental doses were 0.75 mg. There was a daily dosing limit of 27 mg.

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.

Safety was established in an open-label, “real world” 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. Unlike other IV opioids, oliceridine has a maximum recommended daily dose of 27 mg.

Sources: FDA press release, August 7, 2020; Trevena press release, August 10, 2020.