Oliceridine (Olinvyk), a potent μ-opioid receptor agonist, received United States Food and Drug Administration (US-FDA) approval on 7 August 2020 for the management of moderate to severe acute pain in adults.
Oliceridine (Olinvyk), a potent μ-opioid receptor agonist, received United States Food and Drug Administration (US-FDA) approval on 7 August 2020 for the management of moderate to severe acute pain in adults. [1]
Compared to conventional opioids such as morphine, oliceridine has a promising potential to offer comparable analgesia, and a wider therapeutic window at a comparable or decreased risk of opioid-related adverse effects (constipation and respiratory depression). [2,3]
Pharmacological Class: μ-opioid receptor agonist
Oliceridine is a G protein-selective agonist at the µ-opioid receptor. [3] It primarily activates the G-protein pathway with minimal receptor phosphorylation and recruitment of β-arrestin. [2] Its major therapeutic action is analgesia. However, the precise mechanism of its pain-relieving action is not clearly known.
Throughout the brain and spinal cord, specific central nervous system (CNS) opioid receptors for endogenous compounds with opioid-like activity have been detected that are thought to play a pivotal role in the analgesic effects of oliceridine.
Like other full opioid agonists, no ceiling effect to analgesia is seen for the opioid oliceridine. Clinically, the dosage is titrated to offer adequate pain relief and may be restricted by noxious reactions, including CNS and respiratory depression. [4]
Oliceridine should be used for intravenous
administration only. [4] The maximum
recommended daily dose limit of this μ-opioid receptor agonist is 27
milligrams. [1] Single doses higher than 3 mg should not be given as it has not
been yet investigated. [4]
Absorption
The oral bioavailability of oliceridine is low (5.77%). The half-life of oliceridine is 1.3-3 hours while its metabolites have a substantially longer half-life (~44 hours). None of these metabolites have any significant activity at the µ-opioid receptor.
Distribution
The opioid oliceridine possesses an extensive tissue distribution since its mean steady-state volume of distribution ranges between 90-120 L. In humans, the plasma protein binding is found to be 77%.
Metabolism
In the liver, oliceridine is considerably metabolized by CYP3A4 and CYP2D6 P450 hepatic enzymes, with minor contributions from CYP2C9 and CYP2C19 into inactive metabolites.
With increasing dose, the mean clearance of oliceridine declines slightly. Particularly at doses higher than 2 mg, a greater than- proportional exposure is developed.
Oliceridine possesses a low renal clearance (2.2 – 5.1% of total clearance) since the percent of unchanged drug eliminated via the urine is low (0.97-6.75% of the dose). Kidney impairment does not affect the clearance of oliceridine. Its pharmacokinetics does not alter significantly (except for peak concentrations) when given over different infusion times.
Excretion
Approximately 70% of oliceridine is eliminated in the urine. Elimination of the remaining 30 % occurs via the feces. In the urine, only a small amount of unchanged drug (0.97-6.75% of a dose) is found.
Contraindicated in patients having the following conditions:
Due to the additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants substantially raises the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Concomitant usage of anticholinergics may enhance the risk of urinary retention and severe constipation. This may develop paralytic ileus in patients.
Concomitant use may considerably minimize the analgesic effect of oliceridine and/or precipitate withdrawal symptoms.
The opioid agonist can remarkably minimize the efficacy of diuretics by stimulating the release of antidiuretic hormone.
Concomitant usage of the opioid with other drugs that affect the serotonergic neurotransmitter system can substantially develop serotonin syndrome.
The opioid may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an elevated degree of respiratory depression.
Concomitant administration of moderate to strong CYP3A4 inhibitors can raise the plasma concentration of oliceridine. This, in turn, leads to prolonged or elevated opioid adverse reactions.
Concomitant administration of a moderate to strong CYP2D6 inhibitor can elevate the plasma concentration of oliceridine leading to increased or prolonged opioid effects.
(Inhibitors of CYP3A4: Macrolide antibiotics [e.g., erythromycin], azole-antifungal agents [e.g., ketoconazole, itraconazole], antiretroviral agents, selective serotonin reuptake inhibitors [SSRIs], protease inhibitors [e.g., ritonavir], NS3/4A inhibitors, Inhibitors of CYP2D6: Paroxetine, fluoxetine, quinidine, bupropion).
Oliceridine is primarily metabolized by both CYP3A4 and CYP2D6. Suppression of both the pathways can potentially enhance the plasma concentrations of the opioid, and prolong its noxious reactions.
Concomitant use of oliceridine and CYP3A4 inducers can considerably reduce the plasma concentration of oliceridine. This reduces the efficacy or onset of a withdrawal syndrome in individuals who have developed physical dependence to the opioid agonist.
The most common side effects are: [1, 4]
Other adverse reactions that may occur: [4]
Olinvyk (oliceridine) can treat moderate to severe acute pain in adults, where the pain is severe enough to require an intravenous opioid and for whom alternative treatments are not adequate.
Randomized, controlled and open-label trials were conducted to investigate the safety and efficacy of oliceridine in 1,535 patients who had undergone bunion surgery or abdominal surgery and had moderate to severe acute pain. At the approved doses, patients managed with oliceridine therapy reported minimized pain in comparison to placebo. [1]
Intravenous oliceridine is safe and well-tolerated for the
management of moderate to severe acute pain
A phase 3, open-label, multi-center study (ATHENA) was carried out to explore the safety and tolerability of intravenous oliceridine for managing moderate to severe acute pain in a broad, real-world patient population, including postoperative surgical patients and non-surgical patients with painful medical conditions.
The findings reported a prompt reduction in NRS pain score was offered by oliceridine which was maintained till the end of treatment. No deaths or significant cardio respiratory events were witnessed. The incidence of adverse events leading to early discontinuation and serious adverse events were 2% and 3%, respectively. Nausea, constipation, and vomiting were the most common treatment-emergent adverse events (mild or moderate severity) and probably related to oliceridine in 33% of patients. [6]
Comments (2)