Oliceridine

Oliceridine, sold under the brand name Olinvyk, is an opioid medication that is used for the treatment of moderate to severe acute pain in adults.[1] It is given by intravenous (IV) injection.[1]

Oliceridine
Clinical data
Trade namesOlinvyk
Other namesTRV-130
License data
Routes of
administration		Intravenous
ATC code
  • none
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC22H30N2O2S
Molar mass386.55 g·mol−1
3D model (JSmol)

Medical uses

Oliceridine is indicated for short-term intravenous use in hospitals or other controlled clinical settings, such as during inpatient and outpatient procedures.[1] It is not indicated for at-home use.[1]

Adverse effects

The safety profile of oliceridine is similar to other opioids.[1] As with other opioids, the most common side effects of oliceridine are nausea, vomiting, dizziness, headache and constipation.[1] Prolonged use of opioid analgesics during pregnancy can result in neonatal opioid withdrawal syndrome.[1]

Olinvyk carries a boxed warning about addiction, abuse and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; and risks from concomitant use with benzodiazepines or other central nervous system depressants.[1] Unlike other opioids for intravenous administration, Olinvyk has a maximum recommended daily dose limit of 27 milligrams.[1]

Contraindications

Oliceridine should not be given to people with significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected gastrointestinal obstruction; or known hypersensitivity to the medication.[1]

Pharmacology

Pharmacodynamics

Oliceridine is a μ-opioid receptor biased agonist developed by Trevena. In cell-based (in vitro) research, oliceridine elicits robust G protein signaling, with potency and efficacy similar to that of morphine, but with less β-arrestin 2 recruitment and receptor internalization [2]. However, recent reports highlight that this might be due to its low intrinsic efficacy [3], rather than functional selectivity or 'G protein bias' as initially reported. In vivo, it may have fewer adverse effects (including respiratory depression and constipation) compared with morphine.[4][5][6] In general, in vitro potency does not guarantee any clinical relevance in humans.[7]

History

A total of 1,535 participants with moderate to severe acute pain were treated with oliceridine in controlled and open-label trials.[1] Its safety and efficacy were established by comparing oliceridine to placebo in randomized, controlled studies of participants who had undergone bunion surgery or abdominal surgery.[1] Participants administered oliceridine reported decreased pain compared to placebo at the approved doses.[1]

Society and culture

An advisory committee of the U.S. Food and Drug Administration (FDA) voted against the approval of oliceridine in 2018, due to concerns that the benefit of the drug did not exceed the risk. The risks of oliceridine include prolongation of the QT interval on the ECG, and depression of the respiratory drive (which could cause a person to stop breathing).[8] As a result of the committee's vote, the FDA declined to approve oliceridine, citing safety concerns.[9]

Oliceridine was approved for medical use in the United States in August 2020.[1] The FDA granted approval of Olinvyk to Trevena Inc.[1]

See also

References
  1. "FDA Approves New Opioid for Intravenous Use in Hospitals, Other Controlled Clinical Settings". U.S. Food and Drug Administration (FDA) (Press release). 7 August 2020. Retrieved 7 August 2020. This article incorporates text from this source, which is in the public domain.
  2. DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD (March 2013). "A G protein-biased ligand at the μ-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine". Journal of Pharmacology and Experimental Therapeutics. 344 (3): 708–17. doi:10.1124/jpet.112.201616. PMID 23300227. S2CID 8785003.
  3. Gillis, A; Gondin, AB; Kliewer, A; Sanchez, J; Lim, HD; Alamein, C; Manandhar, P; Santiago, M; Fritzwanker, S; Schmiedel, F; Katte, TA; Reekie, T; Grimsey, NL; Kassiou, M; Kellam, B; Krasel, C; Halls, ML; Connor, M; Lane, JR; Schulz, S; Christie, MJ; Canals, M (31 March 2020). "Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists". Science Signaling. 13 (625): eaaz3140. doi:10.1126/scisignal.aaz3140. PMID 32234959. S2CID 214771721.
  4. Chen XT, Pitis P, Liu G, Yuan C, Gotchev D, Cowan CL, Rominger DH, Koblish M, Dewire SM, Crombie AL, Violin JD, Yamashita DS (subscription required) (October 2013). "Structure-Activity Relationships and Discovery of a G Protein Biased μ Opioid Receptor Ligand, [(3-Methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the Treatment of Acute Severe Pain". Journal of Medicinal Chemistry. 56 (20): 8019–31. doi:10.1021/jm4010829. PMID 24063433.CS1 maint: uses authors parameter (link)
  5. Soergel DG, Subach RA, Sadler B, Connell J, Marion AS, Cowan C, Violin JD, Lark MW (October 2013). "First clinical experience with TRV130: Pharmacokinetics and pharmacodynamics in healthy volunteers". The Journal of Clinical Pharmacology. 54 (3): 351–7. doi:10.1002/jcph.207. PMID 24122908.
  6. Staff (1 October 2015). "Acute Postoperative Pain". Genetic Engineering & Biotechnology News (Paper). 35 (17): 40.
  7. Waldman, SA (July 2002). "Does potency predict clinical efficacy? Illustration through an antihistamine model". Annals of Allergy, Asthma & Immunology. 89 (1): 7–11, quiz 11-2, 77. doi:10.1016/S1081-1206(10)61904-7. PMID 12141724.
  8. "FDA Panel Votes Against Analgesic Oliceridine". www.medpagetoday.com. MedPage Today, LLC. 11 October 2018. Retrieved 23 December 2018.
  9. "FDA rejects Trevena's painkiller oliceridine | FierceBiotech". www.fiercebiotech.com. Questex LLC. Retrieved 23 December 2018.
  • "Oliceridine". Drug Information Portal. U.S. National Library of Medicine.
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