Oliceridine, sold under the brand name Olinvyk, is an
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
medication that is used for the treatment of moderate to severe acute
pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
in adults.
[ ] It is given by
intravenous
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
(IV) injection.
The most common side effects include nausea, vomiting, dizziness, headache, constipation, itchy skin and low oxygen levels in blood.
It was approved for medical use in the United States in August 2020.
[ ]
Medical uses
Oliceridine is
indicated
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...
for short-term intravenous use in hospitals or other controlled clinical settings, such as during inpatient and outpatient procedures.
It is not indicated for at-home use.
Adverse effects
The safety profile of oliceridine is similar to other opioids.
As with other opioids, the most common side effects of oliceridine are nausea, vomiting, dizziness, headache and constipation.
Prolonged use of opioid analgesics during pregnancy can result in neonatal opioid withdrawal syndrome.
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.
Unlike other opioids for intravenous administration, Olinvyk has a maximum recommended daily dose limit of 27 milligrams.
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.
Pharmacology
Pharmacodynamics
Oliceridine is a
μ-opioid receptor
The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(''mu'')-opioid peptide (MOP) receptors. The prototypical ...
biased agonist
Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand (biochemistry), ligand-dependent selectivity for certain signal transduction pathway ...
developed by
Trevena. In cell-based (''in vitro'') research, oliceridine elicits robust
G protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their act ...
signaling
In signal processing, a signal is a function that conveys information about a phenomenon. Any quantity that can vary over space or time can be used as a signal to share messages between observers. The ''IEEE Transactions on Signal Processing'' ...
, with
potency
Potency may refer to:
* Potency (pharmacology), a measure of the activity of a drug in a biological system
* Virility
* Cell potency, a measure of the differentiation potential of stem cells
* In homeopathic dilutions, potency is a measure of how ...
and
efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...
similar to that of
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
, but with less
β-arrestin 2
Beta-arrestin-2, also known as arrestin beta-2, is an intracellular protein that in humans is encoded by the ''ARRB2'' gene.
Members of arrestin/beta-arrestin protein family are thought to participate in agonist-mediated desensitization of G prot ...
recruitment and
receptor internalization.
However, recent reports highlight that this might be due to its low intrinsic efficacy, rather than functional selectivity or 'G protein bias' as initially reported. ''In vivo'', it may have fewer
adverse effect
An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complica ...
s (including respiratory depression and constipation) compared with
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
.
In general, ''in vitro'' potency does not guarantee any clinical relevance in humans.
History
A total of 1,535 participants with moderate to severe acute pain were treated with oliceridine in controlled and open-label trials.
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.
Participants administered oliceridine reported decreased pain compared to placebo at the approved doses.
The U.S.
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(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.
The trials were conducted at 53 sites in the United States.
Trials 1 enrolled participants who underwent bunion surgery.
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 through the vein.
Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.
All participants were allowed to use a rescue pain medication, if the pain was not well controlled using the trial medications.
Trial 2 enrolled participants who underwent surgical removal of abdominal wall fat (abdominoplasty) and had moderate to severe pain.
Participants were randomly assigned to receive oliceridine, placebo or an approved drug to treat pain (morphine) for 24 hours through the vein.
Neither the participants nor the health care providers knew which treatment was being given until after the trial was completed.
All participants were allowed to use a rescue pain medication, if the pain was not well controlled using the trial medications.
To assess the benefits of oliceridine, participants used a numerical scale to score how severe the pain was after the surgery.
The scores for the participants receiving oliceridine were compared to the scores for the participants who received placebo and those who received morphine.
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.
Data from this trial were used only to assess the side effects of oliceridine.
Oliceridine was approved for medical use in the United States in August 2020.
The FDA granted approval of Olinvyk to Trevena Inc.
Society and culture
Legal status
An advisory committee of the U.S.
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(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
The QT interval is a measurement made on an electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the Q wave to the end of the T wave, and approximates to the time taken ...
on the
ECG
Electrocardiography is the process of producing an electrocardiogram (ECG or EKG), a recording of the heart's electrical activity. It is an electrogram of the heart which is a graph of voltage versus time of the electrical activity of the hear ...
, and
depression of the respiratory drive (which could cause a person to stop breathing).
As a result of the committee's vote, the FDA declined to approve oliceridine, citing safety concerns.
Oliceridine was approved for medical use in the United States in August 2020.
The FDA granted approval of Olinvyk to Trevena Inc.
The DEA issued an interim final rule on October 30, 2020, designating oliceridine as CSA Schedule II (DEA Code 9245).
See also
*
SHR9352
SHR9352 is a drug which acts as a potent and selective biased agonist at the μ-opioid receptor, selective for activation of the G-protein signalling pathway over β-arrestin 2 recruitment. It was structurally derived from oliceridine by replaci ...
*
TRV734
TRV734 is a drug developed by Trevena Inc which acts as a biased agonist at the μ-opioid receptor, selective for activation of the G-protein signalling pathway over β-arrestin 2 recruitment. It is closely related to oliceridine
Oliceridine ...
References
External links
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