Oliceridine

{{Short description|Opioid analgesic drug}} {{cs1 config|name-list-style=vanc}} {{Infobox drug | drug_name = | INN = | caption2 = 3D representation of an oliceridine molecule | type =  | image = TRV130.svg | image_class = skin-invert-image | image_class2 = bg-transparent | width = 250px | alt = | caption = Molecular structure of oliceridine | image2 = Oliceridine 3D.png | pronounce = OH li SER i deen | tradename = Olinvyk | Drugs.com = {{drugs.com|ppa|oliceridine}} | MedlinePlus = | licence_CA =  | licence_EU =  | DailyMedID = Oliceridine | licence_US =  | pregnancy_AU =  | pregnancy_AU_comment = | pregnancy_category = | dependency_liability = | addiction_liability = | routes_of_administration = Intravenous<ref>{{cite web | title=Olinvyk- oliceridine injection, solution | website=DailyMed | date=18 August 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ce167984-8b9d-40b7-84ce-d0f33fff1eaa#LINK_5124ccc6-4102-466b-ad71-15d663677a4a | access-date=16 September 2020}}</ref> | class = | ATCvet = | ATC_prefix = N02 | ATC_suffix = AX07 | ATC_supplemental =  | legal_AU =  | legal_AU_comment = | legal_BR =  | legal_BR_comment = | legal_CA =  | legal_CA_comment = | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Schedule II | legal_US_comment = | legal_EU = | legal_EU_comment = | legal_UN =  | legal_UN_comment = | legal_status =

| IUPAC_name = ''N''-[(3-Methoxythiophen-2-yl)methyl]-2-[(9''R'')-9-pyridin-2-yl-6-oxaspiro[4.5]decan-9-yl]ethanamine | C = 22 | H = 30 | N = 2 | O = 2 | S = 1 | SMILES = COc1ccsc1CNCC[C@]2(CCOC3(CCCC3)C2)c4ccccn4 | StdInChI = 1S/C22H30N2O2S/c1-25-18-7-15-27-19(18)16-23-13-10-21(20-6-2-5-12-24-20)11-14-26-22(17-21)8-3-4-9-22/h2,5-7,12,15,23H,3-4,8-11,13-14,16-17H2,1H3/t21-/m1/s1 | StdInChI_comment = | StdInChIKey = DMNOVGJWPASQDL-OAQYLSRUSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''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.<ref name="FDA PR">{{cite press release | title=FDA Approves New Opioid for Intravenous Use in Hospitals, Other Controlled Clinical Settings | website=U.S. Food and Drug Administration (FDA) | date=7 August 2020 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-opioid-intravenous-use-hospitals-other-controlled-clinical-settings | archive-url=https://web.archive.org/web/20200808054033/https://www.fda.gov/news-events/press-announcements/fda-approves-new-opioid-intravenous-use-hospitals-other-controlled-clinical-settings | archive-date=August 8, 2020 | access-date=7 August 2020}} {{PD-notice}}</ref> It is given by intravenous (IV) injection.<ref name="FDA PR" />

The most common side effects include nausea, vomiting, dizziness, headache, constipation, itchy skin and low oxygen levels in blood.<ref name="FDA snapshot" />

It was approved for medical use in the United States in August 2020.<ref name="FDA snapshot">{{cite web | title=Drug Trials Snapshots: Olinvyk | website=U.S. Food and Drug Administration (FDA) | date=7 August 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-olinvyk | archive-url=https://web.archive.org/web/20200924045202/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-olinvyk | archive-date=September 24, 2020 | access-date=16 September 2020}} {{PD-notice}}</ref>

== Medical uses == Oliceridine is indicated for short-term intravenous use in hospitals or other controlled clinical settings, such as during inpatient and outpatient procedures.<ref name="FDA PR" /> It is not indicated for at-home use.<ref name="FDA PR" />

== Adverse effects == The safety profile of oliceridine is similar to other opioids.<ref name="FDA PR" /> As with other opioids, the most common side effects of oliceridine are nausea, vomiting, dizziness, headache and constipation.<ref name="FDA PR" /> Prolonged use of opioid analgesics during pregnancy can result in neonatal opioid withdrawal syndrome.<ref name="FDA PR" />

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.<ref name="FDA PR" /> Unlike other opioids for intravenous administration, Olinvyk has a maximum recommended daily dose limit of 27 milligrams.<ref name="FDA PR" />

== 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.<ref name="FDA PR" />

== 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.<ref name="pmid23300227">{{cite journal | vauthors = 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 | display-authors = 6 | title = A G protein-biased ligand at the μ-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 344 | issue = 3 | pages = 708–717 | date = March 2013 | pmid = 23300227 | doi = 10.1124/jpet.112.201616 | s2cid = 8785003 }}</ref> It has been suggested that this might be due to its low intrinsic efficacy,<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists | journal = Science Signaling | volume = 13 | issue = 625 | article-number = eaaz3140 | date = March 2020 | pmid = 32234959 | doi = 10.1126/scisignal.aaz3140 | s2cid = 214771721 | url = https://nottingham-repository.worktribe.com/output/4193457 | hdl = 1959.4/unsworks_81586 | hdl-access = free }}</ref> rather than functional selectivity or 'G protein bias', although the validity of that conclusion has also been questioned.<ref>{{cite journal | vauthors = Stahl EL, Bohn LM | title = Low Intrinsic Efficacy Alone Cannot Explain the Improved Side Effect Profiles of New Opioid Agonists | journal = Biochemistry | volume = 61 | issue = 18 | pages = 1923–1935 | date = September 2022 | pmid = 34468132 | doi = 10.1021/acs.biochem.1c00466 | pmc = 8885792 }}</ref> ''In vivo'', it may have fewer adverse effects (including respiratory depression and constipation) compared with morphine.<ref name="pmid24063433">{{cite journal | vauthors = Chen XT, Pitis P, Liu G, Yuan C, Gotchev D, Cowan CL, Rominger DH, Koblish M, Dewire SM, Crombie AL, Violin JD, Yamashita DS | display-authors = 6 | title = 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 = Journal of Medicinal Chemistry | volume = 56 | issue = 20 | pages = 8019–8031 | date = October 2013 | pmid = 24063433 | doi = 10.1021/jm4010829 }}</ref><ref name="pmid24122908">{{cite journal | vauthors = Soergel DG, Subach RA, Sadler B, Connell J, Marion AS, Cowan CL, Violin JD, Lark MW | display-authors = 6 | title = First clinical experience with TRV130: pharmacokinetics and pharmacodynamics in healthy volunteers | journal = Journal of Clinical Pharmacology | volume = 54 | issue = 3 | pages = 351–357 | date = March 2014 | pmid = 24122908 | doi = 10.1002/jcph.207 | s2cid = 25049515 }}</ref><ref>{{Cite journal|last=Staff|date=1 October 2015|title=Acute Postoperative Pain|journal=Genetic Engineering & Biotechnology News|type=Paper|volume=35|issue=17|page=40}}</ref> In general, ''in vitro'' potency does not guarantee any clinical relevance in humans.<ref name="Waldman">{{cite journal | vauthors = Waldman SA | title = Does potency predict clinical efficacy? Illustration through an antihistamine model | journal = Annals of Allergy, Asthma & Immunology | volume = 89 | issue = 1 | pages = 7–11; quiz 11–2, 77 | date = July 2002 | pmid = 12141724 | doi = 10.1016/S1081-1206(10)61904-7 }}</ref>

== History == A total of 1,535 participants with moderate to severe acute pain were treated with oliceridine in controlled and open-label trials.<ref name="FDA PR" /> 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.<ref name="FDA PR" /> Participants administered oliceridine reported decreased pain compared to placebo at the approved doses.<ref name="FDA PR" />

The U.S. Food and Drug Administration (FDA) approved oliceridine based on evidence from three clinical trials (Trial 1/NCT02815709, Trial 2/NCT02820324 and Trial 3) of 1558 participants 18 to 89 years old who were in need of pain medication.<ref name="FDA snapshot" /> The trials were conducted at 53 sites in the United States.<ref name="FDA snapshot" />

Trial 1 enrolled participants who underwent bunion surgery.<ref name="FDA snapshot" /> Participants with moderate to severe post-surgical pain were randomly assigned to receive oliceridine, placebo or an approved drug to treat pain (morphine) for 48 hours intravenously.<ref name="FDA snapshot" /> Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.<ref name="FDA snapshot" /> All participants were allowed to use a rescue pain medication, if the pain was not well controlled using the trial medications.<ref name="FDA snapshot" />

Trial 2 enrolled participants who underwent surgical removal of abdominal wall fat (abdominoplasty) and had moderate to severe pain.<ref name="FDA snapshot" /> Participants were randomly assigned to receive oliceridine, placebo or an approved drug to treat pain (morphine) for 24 hours intravenously.<ref name="FDA snapshot" /> Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.<ref name="FDA snapshot" /> All participants were allowed to use a rescue pain medication, if the pain was not well controlled using the trial medications.<ref name="FDA snapshot" />

To assess the benefits of oliceridine, participants used a numerical scale to score how severe the pain was after the surgery.<ref name="FDA snapshot" /> The scores for the participants receiving oliceridine were compared to the scores for the participants who received placebo and those who received morphine.<ref name="FDA snapshot" />

In the third trial, participants who had pain following various type of surgeries or due to a medical condition received at least one dose of oliceridine.<ref name="FDA snapshot" /> Data from this trial were used only to assess the side effects of oliceridine.<ref name="FDA snapshot" />

Oliceridine was approved for medical use in the United States in August 2020.<ref name="FDA PR" /> The FDA granted approval of Olinvyk to Trevena Inc.<ref name="FDA PR" />

==Society and culture== === Legal status === 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).<ref name="FDA Vote Against 18">{{cite web |title=FDA Panel Votes Against Analgesic Oliceridine |url=https://www.medpagetoday.com/painmanagement/opioids/75668 |website=www.medpagetoday.com |publisher=MedPage Today, LLC |access-date=23 December 2018 |language=en |date=11 October 2018}}</ref> As a result of the committee's vote, the FDA declined to approve oliceridine, citing safety concerns.<ref name="FDA rejection 2018">{{cite web |title=FDA rejects Trevena's painkiller oliceridine {{!}} FierceBiotech |url=https://www.fiercebiotech.com/biotech/fda-rejects-trevena-s-painkiller-oliceridine |website=www.fiercebiotech.com |date=5 November 2018 |publisher=Questex LLC |access-date=23 December 2018 }}</ref><ref name="pmid31010646">{{cite journal | vauthors = Azzam AA, McDonald J, Lambert DG | title = Hot topics in opioid pharmacology: mixed and biased opioids | journal = British Journal of Anaesthesia | volume = 122 | issue = 6 | pages = e136–e145 | date = June 2019 | pmid = 31010646 | doi = 10.1016/j.bja.2019.03.006 | hdl-access = free | s2cid = 128360210 | hdl = 2381/43829 }}</ref>

Oliceridine was approved for medical use in the United States in August 2020.<ref name="FDA PR" /> The FDA granted approval of Olinvyk to Trevena Inc.<ref name="FDA PR" />

The DEA issued an interim final rule on October 30, 2020, designating oliceridine as CSA Schedule II (DEA Code 9245).{{fcn|date=July 2022}}

== References == {{Reflist}}

== External links == * {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/oliceridine | archive-url = https://web.archive.org/web/20220123152459/https://druginfo.nlm.nih.gov/drugportal/name/oliceridine | archive-date = January 23, 2022 | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Oliceridine }} * {{ClinicalTrialsGov|NCT02815709|Study of Oliceridine (TRV130) for the Treatment of Moderate to Severe Acute Pain After Bunionectomy (APOLLO-1)}} * {{ClinicalTrialsGov|NCT02820324|Study of Oliceridine (TRV130) for the Treatment of Moderate to Severe Acute Pain After Abdominoplasty}}

Category:Analgesics Category:Biased ligands Category:Mu-opioid receptor agonists Category:2-Pyridyl compounds Category:Spiro compounds Category:Thiophenes