General Information

Olinvyk (oliceridine) is an opioid agonist.

Olinvyk is specifically indicated for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate.

Olinvyk is supplied as a solution for intravenous administration. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse. Initiate treatment with a 1.5 mg dose. For patient controlled analgesia (PCA), recommended demand dose is 0.35 mg, with a 6-minute lock-out. A demand dose of 0.5 mg may be considered. Supplemental doses of 0.75 mg can be administered, beginning 1 hour after the initial dose, and hourly thereafter, as needed. Do not stop Olinvyk in a physically-dependent patient.

Mechanism of Action

Olinvyk (oliceridine) is an opioid agonist and is relatively selective for the mu-opioid receptor. The principal therapeutic action of oliceridine is analgesia. Like all full opioid agonists, there is no ceiling effect to analgesia for oliceridine. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory, and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

Side Effects

Adverse effects associated with the use of Olinvyk may include, but are not limited to, the following:

• nausea
• vomiting
• dizziness
• headache
• constipation
• pruritus
• hypoxia

The Olinvyk drug label comes with the following Black Box Warning: • Olinvyk exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for the development of behaviors or conditions. • Serious, life-threatening, or fatal respiratory depression may occur. Monitor for respiratory depression, especially during initiation or following a dose increase. • Prolonged use of Olinvyk during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. • Concomitant use of Olinvyk with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

Clinical Trial Results

The FDA approval of Olinvyk was based on two randomized, double-blind, placebo- and morphine-controlled studies of patients with moderate to severe acute pain following orthopedic surgery-bunionectomy or plastic surgery-abdominoplasty. In each study, pain intensity was measured using a patient-reported numeric rating scale (11-point numerical scale ranging from 0- 10, where zero corresponds to no pain and 10 corresponds to worst pain imaginable). In each study, patients were randomized to one of three Olinvyk treatment regimens, a placebo-control regimen, or a morphine-control regimen. Each blinded treatment regimen consisted of a loading dose, incremental doses delivered as needed via patient-controlled analgesia (PCA) device, and supplemental doses, beginning 1 hour after the initial dose, and hourly thereafter, as needed. The loading dose for all Olinvyk treatment regimens was 1.5 mg; demand doses were 0.1, 0.35 or 0.5 mg, according to the assigned treatment group; supplemental doses were 0.75 mg. The loading dose for the morphine treatment regimen was 4 mg; the demand dose was 1 mg; supplemental doses were 2 mg. The placebo-control regimen was volume-matched. A lockout interval of 6 minutes was used for all PCA regimens. 

Study 1 – Orthopedic Surgery - Bunionectomy:

A total of 389 patients (placebo n=79, Olinvyk 0.1 mg n=76, Olinvyk 0.35 mg n=79, Olinvyk 0.5 mg n=79, and morphine n=76), 19-74 years of age, with moderate to severe acute pain following orthopedic surgery-bunionectomy, were treated for up to 48 hours in Study 1. Treatment began after discontinuation of regional anesthesia in patients with pain intensity of ≥4 on a 0-10 numeric rating scale [NRS] within 9 hours after discontinuation of regional anesthesia. The analgesic effects were measured using the Summed Pain Intensity Differences over 48 hours (SPID-48). The mean (SD) baseline pain intensity score was 6.7. A statistically significantly greater analgesic effect was observed in both 0.35 mg and 0.5 mg Olinvyk treatment groups, compared to the placebo group. In Study 1, 60% of patients in the Olinvyk 0.35 mg treatment group, and 63% of patients in the Olinvyk 0.5 mg treatment group reached the maximum recommended total cumulative daily dosage of 27 mg. The median (minimum) time to reach the 27 mg maximum recommended cumulative total daily dosage was 15.8 (9.1) hours for patients in the Olinvyk 0.35 mg treatment group, and 13.6 (6.8) hours for patients in the Olinvyk 0.5 mg treatment group.

Study 2 – Plastic Surgery - Abdominoplasty

A total of 401 patients (placebo n=81, Olinvyk 0.1 mg n=77, Olinvyk 0.35 mg n=80, Olinvyk 0.5 mg n=80, and morphine n=83), 20-71 years of age, with moderate to severe acute pain following plastic surgery-abdominoplasty, were treated for up to 24 hours in Study 2. Treatment began after discontinuation of general anesthesia in patients with NRS ≥5 within 4 hours after end of surgery. The analgesic effects were measured using the Summed Pain Intensity Differences over 24 hours (SPID-24). The majority of patients treated with Olinvyk (0.1 mg treatment group: 86%; 0.35 mg treatment group: 90%; 0.5 mg treatment group: 87%) completed the randomized treatment period without discontinuing study medication (compared to 74% of patients treated with placebo). Eleven percent (11%), 3%, and 5% of patients in the Olinvyk 0.1 mg, 0.35 mg and 0.5 mg treatment groups, respectively, discontinued study medication due to lack of efficacy (compared to 22% of patients treated with placebo). In the Olinvyk 0.1 mg, 0.35 mg, and 0.5 mg treatment groups, 31%, 21%, and 18% of patients, respectively, used protocol-specified rescue medication etodolac, compared to 49% in patients treated with placebo. The mean (SD) baseline pain intensity score was 7.3. A statistically significantly greater analgesic effect was observed in the Olinvyk 0.5 mg and 0.35 mg treatment groups, compared to the placebo group. The analgesic effect was not significantly better in the Olinvyk 0.1 mg treatment group than in the placebo group.