IMPORTANT SAFETY INFORMATION
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL
OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER
CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS
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
OLINVYK, and monitor all patients regularly for the development of behaviors or conditions.
Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK.
Monitor for respiratory depression, especially during initiation of OLINVYK or following a
Prolonged use of OLINVYK during pregnancy can result in neonatal opioid withdrawal syndrome,
which may be life-threatening if not recognized and treated, and requires management
according to protocols developed by neonatology experts. If opioid use is required for a
prolonged period 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 opioids 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.
OLINVYK is a new chemical entity and is indicated in adults for the management of acute pain
severe enough to require an intravenous opioid analgesic and for whom alternative treatments are
Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses,
reserve OLINVYK for use in patients for whom alternative treatment options [e.g., non-opioid
analgesics or opioid combination products]:
Have not been tolerated, or are not expected to be tolerated
Have not provided adequate analgesia, or are not expected to provide adequate analgesia.
The cumulative total daily dose should not exceed 27 mg, as total
daily doses greater than 27 mg may increase the risk for QTc
OLINVYK is contraindicated in patients with:
Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative
Known or suspected gastrointestinal obstruction, including paralytic ileus
Known hypersensitivity to oliceridine (e.g., anaphylaxis)
WARNINGS AND PRECAUTIONS
OLINVYK contains oliceridine, a Schedule II controlled substance, that exposes users to the
risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is
unknown, it can occur in patients appropriately prescribed OLINVYK. Assess risk, counsel, and
monitor all patients receiving opioids.
Serious, life-threatening respiratory depression has been reported with the use of opioids, even
when used as recommended, especially in patients with chronic pulmonary disease, or in elderly,
cachectic and debilitated patients. The risk is greatest during initiation of OLINVYK therapy,
following a dose increase, or when used with other drugs that depress respiration. Proper dosing
of OLINVYK is essential, especially when converting patients from another opioid product to
avoid overdose. Management of respiratory depression may include close observation, supportive
measures, and use of opioid antagonists, depending on the patient’s clinical status.
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and
sleep-related hypoxemia with risk increasing in a dose-dependent fashion. In patients who
present with CSA, consider decreasing the dose of opioid using best practices for opioid taper.
Prolonged use of opioids during pregnancy can result in withdrawal in the neonate that may be
life-threatening. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage
accordingly. Advise pregnant women using OLINVYK for a prolonged period of the risk of neonatal
opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Profound sedation, respiratory depression, coma, and death may result from the concomitant use
of OLINVYK with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine
sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics,
antipsychotics, other opioids, or alcohol). Because of these risks, reserve concomitant
prescribing of these drugs for use in patients for whom alternative treatment options are
inadequate, prescribe the lowest effective dose, and minimize the duration.
OLINVYK was shown to have mild QTc interval prolongation in thorough QT studies where patients
were dosed up to 27 mg. Total cumulative daily doses exceeding 27 mg per day were not studied and may increase the risk for QTc
interval prolongation. Therefore, the cumulative total daily dose of OLINVYK should not exceed
Increased plasma concentrations of OLINVYK may occur in patients with decreased Cytochrome P450
(CYP) 2D6 function or normal metabolizers taking moderate or strong CYP2D6 inhibitors; also in
patients taking a moderate or strong CYP3A4 inhibitor, in patients with decreased CYP2D6
function who are also receiving a moderate or strong CYP3A4 inhibitor, or with discontinuation
of a CYP3A4 inducer. These patients may require less frequent dosing and should be closely
monitored for respiratory depression and sedation at frequent intervals. Concomitant use of
OLINVYK with CYP3A4 inducers or discontinuation of a moderate or strong CYP3A4 inhibitor can
lower the expected concentration, which may decrease efficacy, and may require supplemental
Cases of adrenal insufficiency have been reported with opioid use (usually greater than one
month). Presentation and symptoms may be nonspecific and include nausea, vomiting, anorexia,
fatigue, weakness, dizziness, and low blood pressure. If confirmed, treat with physiologic
replacement doses of corticosteroids and wean patient from the opioid.
OLINVYK may cause severe hypotension, including orthostatic hypotension and syncope in
ambulatory patients. There is increased risk in patients whose ability to maintain blood
pressure has already been compromised by a reduced blood volume or concurrent administration of
certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these
patients for signs of hypotension. In patients with circulatory shock, avoid the use of OLINVYK
as it may cause vasodilation that can further reduce cardiac output and blood pressure.
Avoid the use of OLINVYK in patients with impaired consciousness or coma. OLINVYK should be used
with caution in patients who may be susceptible to the intracranial effects of CO2
retention, such as those with evidence of increased intracranial pressure or brain tumors, as a
reduction in respiratory drive and the resultant CO2 retention can further increase
intracranial pressure. Monitor such patients for signs of sedation and respiratory depression,
particularly when initiating therapy.
As with all opioids, OLINVYK may cause spasm of the sphincter of Oddi, and may cause increases
in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for
OLINVYK may increase the frequency of seizures in patients with seizure disorders and may
increase the risk of seizures in vulnerable patients. Monitor patients with a history of seizure
disorders for worsened seizure control.
Do not abruptly discontinue OLINVYK in a patient physically dependent on opioids. Gradually
taper the dosage to avoid a withdrawal syndrome and return of pain. Avoid the use of mixed
agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g.,
buprenorphine) analgesics in patients who are receiving OLINVYK, as they may reduce the
analgesic effect and/or precipitate withdrawal symptoms.
OLINVYK may impair the mental or physical abilities needed to perform potentially hazardous
activities such as driving a car or operating machinery.
Although self-administration of opioids by patient-controlled analgesia (PCA) may allow each
patient to individually titrate to an acceptable level of analgesia, PCA administration has
resulted in adverse outcomes and episodes of respiratory depression. Health care providers and
family members monitoring patients receiving PCA analgesia should be instructed in the need for
appropriate monitoring for excessive sedation, respiratory depression, or other adverse effects
of opioid medications.
Adverse reactions are described in greater detail in the Prescribing Information.
The most common (incidence ≥10%) adverse reactions in Phase 3 controlled clinical trials were
nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia.
For medical inquiries or to report an adverse event, other safety-related information or product
complaints for a company product, please contact the Trevena Medical Information Contact Center at
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see Full Prescribing Information, including Boxed
References: 1. Data on file. Trevena, Inc; 2020. 2. OLINVYK. Prescribing information.
Trevena, Inc; 2021. 3. Bergese SD, Brzezinski M, Hammer GB, et al. ATHENA: a phase 3, open-label study of
the safety and effectiveness of oliceridine (TRV130), a G-protein selective agonist at the µ-opioid receptor, in
patients with moderate to severe acute pain requiring parenteral opioid therapy. J Pain Res.
2019;12:3113-3126. 4. Gan TJ, Wase L. Oliceridine, a G protein-selective ligand at the µ-opioid receptor,
for the management of moderate to severe acute pain. Drugs Today (Barc). 2020;56(4):269-286.