OLINVYK OLICERIDINE 2 mg/2mL Injection, Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Other opioids class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Oliceridine injection is used as short-term treatment to relieve severe, acute pain (pain that begins suddenly, has a specific cause, and is expected to go away when the cause of the pain is healed) in people who are expected to need an opioid pain medication and who cannot be controlled by the use of alternative pain medications. Oliceridine is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.
Read the full MedlinePlus article ↗- Olinvyk is used in adults to control severe acute pain — the kind that's bad enough to need a strong opioid given directly into a vein. It's not for everyday or long-term pain. You...
- Olinvyk works fast — most people notice some pain relief within 2 to 5 minutes of the first dose. It's given through an IV line only, never by mouth or any other route. Depending o...
- How quickly will it start working, and how is it given?
- The most common side effects are nausea, vomiting, dizziness, constipation, itching, headache, and feeling drowsy — these are typical opioid effects and your team will watch for th...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Oliceridine — tap one for details:
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 4QD397987E
An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
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UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
3 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Olinvyk 2 mg/2mLthis 71308-0021-10 | Trevena, | 10 vials | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11931350 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 11931350 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 11931350 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 9642842 ↗ | Method of use | U-2986 | Mar 23, 2032 |
| US 9642842 ↗ | Method of use | U-2986 | Mar 23, 2032 |
| US 9642842 ↗ | Method of use | U-2986 | Mar 23, 2032 |
| US 8835488 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 9309234 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 8835488 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 9309234 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 8835488 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 9309234 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 11077098 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 11077098 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
| US 11077098 ↗ | Drug substance | U-2986 | Mar 23, 2032 |
Is there a generic version of OLINVYK 2 MG/2 ML VIAL?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
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🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 71308-0021-10 You're viewing this | 10 VIAL, SINGLE-DOSE in 1 CARTON (71308-021-10) / 2 mL in 1 VIAL, SINGLE-DOSE (71308-021-01) | 2020-08-07 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF OLINVYK Addiction, Abuse, and Misuse Because the use of 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 prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions ( 5.1 )] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK, especially during initiation or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of OLINVYK are essential [see Warnings and Precautions ( 5.2 )]. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of OLINVYK and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )].
Neonatal Opioid Withdrawal Syndrome Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions ( 5.4 )]. WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF OLINVYK See full prescribing information for complete boxed warning.
OLINVYK exposes users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and reassess regularly for the development of behaviors or conditions. ( 5.1 ) Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK, especially during initiation or following a dosage increase.
To reduce the risk of respiratory depression, proper dosing and titration of OLINVYK are essential. ( 5.2 ) Concomitant use of OLINVYK 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.
( 5.4 , 7 ) Advise pregnant women using opioids for an extended period of time of the risks of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery. ( 5.3 )
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE OLINVYK is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration [see Warnings and Precautions ( 5.1 )] , and persist over the course of therapy, reserve opioid analgesics, including OLINVYK, for use in patients for whom alternative treatment options are ineffective, not management of pain.
The cumulative total daily dose should not exceed 27 mg, as total daily doses greater than 27 mg may increase the risk for QTc interval prolongation [see Warnings and Precautions ( 5.5 ] . OLINVYK is an opioid agonist indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. ( 1 ) Limitations of Use ( 1 ) Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including OLINVYK, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.( 1 , 5.1 ) The cumulative total daily dose should not exceed 27 mg.
( 2.1 , 2.2 , 5.5 ).
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION For intravenous administration only. OLINVYK should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1 ) Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
Reserve titration to higher doses of OLINVYK for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5 ) Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse and misuse. ( 2.1 , 5.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with OLINVYK.
Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.2 ) Initiate treatment with a 1.5 mg dose. ( 2.2 ) For patient controlled analgesia (PCA), recommended demand dose is 0.35 mg, with a 6-minute lock-out.
A demand dose of 0.5 mg may be considered. ( 2.2 ) Supplemental doses of 0.75 mg can be administered, beginning 1 hour after the initial dose, and hourly thereafter, as needed. ( 2.2 ) Periodically reassess patients receiving OLINVYK to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse.
( 2.3 ) Do not rapidly reduce or abruptly discontinue OLINVYK in a physically-dependent patient. ( 2.4 , 5.14 )
2.1Important Dosage and Administration Instructions For intravenous administration only. OLINVYK should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Individual single doses greater than 3 mg have not been evaluated.
The cumulative daily dose should not exceed 27 mg. OLINVYK 30 mg/30 mL (1mg/mL) vial is intended for patient-controlled analgesia (PCA) use only. Draw OLINVYK directly from the vial into the PCA syringe or IV bag without diluting.
Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions ( 5 )] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of OLINVYK for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Use of OLINVYK beyond 48 hours has not been studied in controlled clinical trials.
There is variability in opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse ( 5.1 )] . Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with OLINVYK.
Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions ( 5 ) ] . Inspect OLINVYK for particulate matter and discoloration prior to administration. The solution is a clear, colorless, preservative free solution for intravenous use.
If visibly opaque particles, discoloration, or other foreign particles are observed, do not use.
2.2Initial Dosage OLINVYK can be administered by a healthcare provider with an initial dose of 1.5 mg. For PCA, the initial dose can be followed by access to patient demand doses with a 6-minute lock-out. The recommended demand dose is 0.35 mg. A demand dose of 0.5 mg may be considered for some patients if the potential benefit…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Injection: clear, colorless, sterile, preservative-free solution for intravenous use supplied as follows: 1 mg/mL, equivalent to 1.3 mg/mL oliceridine fumarate salt, in single-dose, 2 mL, clear glass vials with gray plastic flip-off caps 2 mg/2 mL (1 mg/mL), equivalent to 2.6 mg/2 mL (1.3 mg/mL) oliceridine fumarate salt, in single-dose, 2 mL, clear glass vials with orange plastic flip-off caps 30 mg/30 mL (1 mg/mL), equivalent to 39 mg/30 mL (1.3 mg/mL) oliceridine fumarate salt, in single-patient-use, 30 mL, clear glass vials with purple plastic flip-off caps.
For PCA Use Only. Injection: 1 mg/mL and 2 mg/2 ml (1 mg/mL) in single-dose vials 30 mg/30 mL (1 mg/mL) in single-patient-use vial, For PCA Use Only ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS OLINVYK is contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions ( 5.2 )] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.8 )] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.12 )] Known hypersensitivity to oliceridine (e.g., anaphylaxis) Significant respiratory depression ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus ( 4 ) Known hypersensitivity to oliceridine ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Opioid-Induced Hyperalgesia and Allodynia: Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation. ( 5.7 ) Potential for QT Prolongation with Daily Doses Exceeding 27 mg : May increase risk for QT interval prolongation.
Do not exceed a cumulative daily dose of 27 mg. ( 5.5 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Monitor closely, particularly during initiation and titration. ( 5.8 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement corticosteroids and wean the patient off the opioid.
( 5.9 ) Severe Hypotension : Monitor patients during initiation or titration. Avoid use of OLINVYK in patients with circulatory shock. ( 5.10 ) Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness : Monitor for signs of sedation and respiratory depression.
Avoid the use of OLINVYK in patients with impaired consciousness or coma. ( 5.11 )
5.1Addiction, Abuse, and Misuse OLINVYK contains oliceridine, a Schedule II controlled substance. As an opioid, OLINVYK exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence ( 9 )] . Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OLINVYK.
Addiction can occur at recommended dosages and if the drug is misused or abused [see Drug Abuse and Dependence ( 9 )] . The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see Adverse Reactions ( 6.2 )] .
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing OLINVYK, and monitor all patients receiving OLINVYK for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient.
Patients at increased risk may be prescribed opioids such as OLINVYK, but use in such patients necessitates intensive counseling about the risks and proper use of OLINVYK along with intensive monitoring for signs of addiction, abuse, and misuse. Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing OLINVYK.
Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity. Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
5.2Life-Threatening Respiratory Depression Serious, life-threatening respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid opioid overdose reversal agents (e.g., naloxone, nalmefene), depending on the patient’s clinical status [see Overdosage ( 10.2 )] .
Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of opioids, the risk is greatest during initiation of the…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Life-threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions ( 5.3 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 )] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.7 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.9 )] Severe Hypotension [see Warnings and Precautions ( 5.10 )] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.12 )] Seizures [see Warnings and Precautions ( 5.13 )] Withdrawal [see Warnings and Precautions ( 5.14 )] The most common (incidence ≥10%) adverse reactions in controlled clinical trials (Studies 1 and 2) were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Trevena, Inc. at 1-844-465-4686 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. A total of 1535 patients were treated with OLINVYK in controlled and open-label trials in patients with moderate to severe acute pain. Of these, 1181 patients received a total daily dose ≤27 mg and 354 patients received a total daily dose >27 mg during the first 24-hour treatment period.
Among patients who received a daily dose of >27 mg, 198 patients received a daily dose between 27 mg and 40 mg, and 142 patients received a daily dose >40 mg. The most common adverse drug reactions (≥10%) in controlled efficacy trials (Study 1 and Study 2) were nausea, vomiting, dizziness, headache, constipation, pruritus and hypoxia. Adverse reactions leading to discontinuation of OLINVYK were hypotension, hypoxia, nausea, hypoventilation, oxygen saturation decreased, alanine aminotransferase increased, aspartate aminotransferase increased, electrocardiogram QT prolongation, and urticaria.
In two randomized, double-blind, placebo- and morphine-controlled studies, when stratified by 27 mg daily dosing limit, discontinuation of OLINVYK due to adverse reactions occurred in 4% of patients who received a daily dose ≤ 27 mg, and less than 1% of patients who received a daily dose >27 mg. In these same studies, discontinuation due to adverse reactions occurred in 5% of morphine-treated patients, and no placebo-treated patients. In an open-label safety study, discontinuation of OLINVYK due to adverse drug reactions occurred in 3% of patients who received a daily dose ≤ 27 mg, and 1% of patients who received a daily dose >27 mg.
In two randomized, double-blind, placebo- and morphine-controlled studies in patients with moderate to severe acute pain following either orthopedic surgery-bunionectomy (Study 1), or plastic surgery-abdominoplasty (Study 2), patients received one of three OLINVYK dosing regimens, a morphine- control regimen, or a volume‑matched placebo-control regimen. All dosing regimens were administered via patient-controlled analgesia (PCA), allowing patients to individually titrate the dose available to an acceptable level of analgesia.
Patients were treated for up to 48 hours in the bunionectomy study (Study 1), and for up to 24 hours in the abdominoplasty study(Study 2) [see Clinical Studies ( 14 )]. The loading dose for all OLINVYK treatment regimens was 1.5 mg; demand doses were 0.1, 0.35, or 0.5 mg, according to assigned treatment group; supplemental doses of 0.75 mg were permitted, beginning 1 hour after the loading dose, and hourly thereafter, as needed. The loading dose for the morphine treatment regimen was 4 mg; the deman…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Table 6 includes clinically significant drug interactions with OLINVYK. Table 6: Clinically Significant Drug Interactions with OLINVYK Moderate to Strong Inhibitors of CYP2D6 Clinical Impact: Concomitant administration of a moderate to strong CYP2D6 inhibitor can increase the plasma concentration of oliceridine [see Clinical Pharmacology ( 12.3 )] , resulting in increased or prolonged opioid effects. Intervention: If concomitant use is necessary, patients taking a moderate to strong CYP2D6 inhibitor may require less frequent dosing of OLINVYK.
Monitor closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient’s severity of pain and response to treatment. If a CYP2D6 inhibitor is discontinued, increase of the OLINVYK dosage may be considered until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
Examples: Paroxetine, fluoxetine, quinidine, bupropion Moderate to Strong Inhibitors of CYP3A4 Clinical Impact: The concomitant administration of moderate to strong CYP3A4 inhibitors can increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid adverse reactions. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oliceridine concentration may decrease, resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to oliceridine [see Warnings and Precautions ( 5.14 )] .
Intervention: Caution should be used when administering OLINVYK to patients taking inhibitors of the CYP3A4 enzyme. If concomitant use is necessary, patients taking a CYP3A4 inhibitor may require less frequent dosing. Monitor patients for respiratory depression and sedation at frequent intervals.
If a CYP3A4 inhibitor is discontinued, increase of the OLINVYK dosage may be considered until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir).
Strong and Moderate CYP3A4 Inhibitors and CYP2D6 Inhibitors Clinical Impact: OLINVYK is primarily metabolized by both CYP3A4 and CYP2D6. Compared to inhibition of either metabolic pathway, inhibition of both pathways can result in a greater increase of the plasma concentrations of oliceridine and prolong opioid adverse reactions [See Clinical Pharmacology ( 12.3 )]. Intervention: Patients who are CYP2D6 normal metabolizers taking a CYP2D6 inhibitor, and a strong CYP3A4 inhibitor (or discontinuation of CYP3A4 inducers) may require less frequent dosing.
Patients who are known CYP2D6 poor metabolizers and taking a CYP3A4 inhibitor (or discontinuation of CYP3A4 inducers) may require less frequent dosing. These patients should be closely monitored for respiratory depression and sedation at frequent intervals, and subsequent doses should be based on the patient’s severity of pain and response to treatment. Examples: Inhibitors of CYP3A4: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole, itraconazole), anti-retroviral agents, selective serotonin re-uptake inhibitors (SSRIs), protease inhibitors (e.g., ritonavir), NS3/4A inhibitors.
Inhibitors of CYP2D6: Paroxetine, fluoxetine, quinidine, bupropion Inducers of CYP3A4 Clinical Impact: The concomitant use of OLINVYK and CYP3A4 inducers can decrease the plasma concentration of oliceridine [see Clinical Pharmacology ( 12.3 )] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oliceridine. [see Warnings and Precautions ( 5.14 )] . After stopping a CYP3A4 inducer, as the effects of the inducer decline, the oliceridine plasma concentration may increase [see Clinical Pharmacology ( 12.3 )] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.
Intervent…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy : May cause fetal harm ( 8.1 ) Decreased CYP2D6 function: Patients may require less frequent dosing. Monitor closely and administer subsequent doses based on severity of pain and patient response. ( 8.8 )
8.1Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may result in neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )] . There are no available data on OLINVYK use in pregnant women to evaluate for a drug-associated risk of major birth defects and miscarriage or adverse maternal outcomes. There are adverse outcomes reported within detal exposure to opioid analgesics (see Clinical Considerations) .
In animal reproductive studies, oliceridine reduced live litter size at birth and increased postnatal pup mortality between birth and Postnatal Day 4 when administered intravenously to rats from organogenesis through weaning at doses producing clinically relevant plasma exposure. Oliceridine had no effect on embryo-fetal development in rats and rabbits when administered intravenously during organogenesis at doses producing plasma exposures 7 and 8 times the estimated plasma exposure at the maximum recommended human dose (MRHD) on an AUC basis, respectively (see Data) .
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.
Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.4 )] . Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, should be available for reversal of opioid induced respiratory depression in the neonate.
OLINVYK is not recommended for use in pregnant women during and immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor.
Monitor neonates exposed to OLINVYK during labor for signs of excess sedation and respiratory depression. Data Animal Data Oliceridine administered via continuous intravenous infusion during the period of embryofetal organogenesis at doses of 6, 12, or 24 mg/kg/day to pregnant rats from Gestation Day (GD) 6 to 20 and 1.5, 3, or 6 mg/kg/day to pregnant rabbits from GD 7 to 29 had no effect on embryonic development at exposures 7 (rats) to 8 times (rabbits) the estimated plasma exposure at the MRHD of 27 mg/day on an AUC basis.
Maternal toxicity (reduced body weight gain) was observed at ≥12 mg/kg/day in rats and at 6 mg/kg/day in rabbits. In a pre−and post−natal development study in rats, oliceridine administered via continuous intravenous infusion at doses of 0.6, 2.4, and 6.0 mg/kg/day from Gestation Day 6 through Lacta…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may result in neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )] . There are no available data on OLINVYK use in pregnant women to evaluate for a drug-associated risk of major birth defects and miscarriage or adverse maternal outcomes. There are adverse outcomes reported within detal exposure to opioid analgesics (see Clinical Considerations) .
In animal reproductive studies, oliceridine reduced live litter size at birth and increased postnatal pup mortality between birth and Postnatal Day 4 when administered intravenously to rats from organogenesis through weaning at doses producing clinically relevant plasma exposure. Oliceridine had no effect on embryo-fetal development in rats and rabbits when administered intravenously during organogenesis at doses producing plasma exposures 7 and 8 times the estimated plasma exposure at the maximum recommended human dose (MRHD) on an AUC basis, respectively (see Data) .
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.
Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.4 )] . Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, should be available for reversal of opioid induced respiratory depression in the neonate.
OLINVYK is not recommended for use in pregnant women during and immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor.
Monitor neonates exposed to OLINVYK during labor for signs of excess sedation and respiratory depression. Data Animal Data Oliceridine administered via continuous intravenous infusion during the period of embryofetal organogenesis at doses of 6, 12, or 24 mg/kg/day to pregnant rats from Gestation Day (GD) 6 to 20 and 1.5, 3, or 6 mg/kg/day to pregnant rabbits from GD 7 to 29 had no effect on embryonic development at exposures 7 (rats) to 8 times (rabbits) the estimated plasma exposure at the MRHD of 27 mg/day on an AUC basis.
Maternal toxicity (reduced body weight gain) was observed at ≥12 mg/kg/day in rats and at 6 mg/kg/day in rabbits. In a pre−and post−natal development study in rats, oliceridine administered via continuous intravenous infusion at doses of 0.6, 2.4, and 6.0 mg/kg/day from Gestation Day 6 through Lactation Day 21 resulted in reduced live litter size at birth at 1.5 times the estimated plasma exposure at the MRHD on an AUC basis and lower pup survival between birth and Postnatal Day 4 at 0.6 times the estimated plasma exposure at the MRHD on a…
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of OLINVYK in pediatric patients has not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Controlled clinical studies of OLINVYK did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Elderly patients (aged 65 years or older) may have increased sensitivity to OLINVYK. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration.
Titrate the dosage of OLINVYK slowly in geriatric patients and monitor for signs of central nervous system and respiratory depression [see Warnings and Precautions ( 5.8 )] .
🆘 Overdosage ▾
10 OVERDOSAGE Clinical Presentation Acute overdose with OLINVYK can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 )] . Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication.
Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures.
While naloxone reversal of OLINVYK’s effects has not been established in humans, some pharmacological effects (analgesia) of oliceridine have been shown to be reversed by naloxone in animals [see Clinical Pharmacology ( 12.2 )] . For clinically significant respiratory or circulatory depression secondary to oliceridine overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. Because the duration of opioid reversal is expected to be less than the duration of oliceridine in OLINVYK injection, carefully monitor the patient until spontaneous respiration is reliably reestablished.
If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the reversal agent administered.
If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the reversal agent should be initiated with care and by titration with smaller than usual doses of the reversal agent.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Oliceridine is a full opioid agonist and is relatively selective for the mu-opioid receptor. The principal therapeutic action of oliceridine is analgesia. Like all full opioid agonists, there is no ceiling effect to analgesia for oliceridine.
Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory, and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
12.2Pharmacodynamics In nonclinical models, the antinociceptive effect of oliceridine can be antagonized by the opioid antagonist naloxone. Effects on the Central Nervous System Opioids produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.
Opioids causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.
Effects on the Gastrointestinal Tract and Other Smooth Muscle Opioids causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation.
Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED). Effects on the Cardiovascular System Opioids produces peripheral vasodilation, which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions ( 6.1 )] . They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility.
The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see Adverse Reactions ( 6.1 )] . Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown.
Overall, the effects of opioids appear to be modestly immunosuppressive. Concentration-Analgesia Relationships In a fixed-dose bunionectomy trial (N=192), the onset of action of OLINVYK (as measured by the two-stopwatch method) was almost immediate (median 1-3 minutes) upon administration of the first dose. Perceptible pain relief was achieved in the majority of patients within 5 minutes after the first dose of OLINVYK.
The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with opioid agonists. The minimu…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Oliceridine is a full opioid agonist and is relatively selective for the mu-opioid receptor. The principal therapeutic action of oliceridine is analgesia. Like all full opioid agonists, there is no ceiling effect to analgesia for oliceridine.
Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory, and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING OLINVYK (oliceridine) injection is a clear, colorless, preservative free solution for intravenous use supplied as follows: NDC# 71308-011-10: 1 mg/mL, sterile solution in single-dose, 2 mL clear glass vials with gray stoppers topped with overseals with gray plastic flip-off caps (carton of 10 vials) NDC# 71308-021-10: 2 mg/2 mL (1 mg/mL), sterile solution in single-dose, 2 mL clear glass vials with gray stoppers topped with overseals with orange plastic flip-off caps (carton of 10 vials) NDC# 71308-301-10: 30 mg/30 mL (1 mg/mL), sterile solution in single-patient-use, 30 mL clear glass vials with gray stoppers topped with overseals with purple plastic flip-off caps (carton of 10 vials).
For PCA Use Only. Store at controlled room temperature 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Protect from freezing.
Protect from light.
📋 Description ▾
11 DESCRIPTION The active ingredient in OLINVYK is oliceridine, an opioid agonist. Oliceridine fumarate is a white to lightly-colored solid that is sparingly soluble in water. The chemical name for oliceridine fumarate is [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl]ethyl})amine fumarate, and the molecular formula is C 22 H 30 N 2 O 2 S·C 4 H 4 O 4 .
The theoretical average molecular mass is 502.62 (fumarate salt) and 386.55 (free base). The structural formula of oliceridine fumarate is: OLINVYK (oliceridine) injection is a clear, colorless, sterile, preservative-free solution, pH 6.4 to 7.4, in a glass vial for intravenous use. Each milliliter of the solution contains 1.0 mg of oliceridine free base (1.3 mg of oliceridine fumarate salt), as well as L-histidine and mannitol, in water for injection.
Structural Formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Addiction, Abuse, and Misuse Inform patients that the use of OLINVYK, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions ( 5.1 )]. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting OLINVYK or when the dosage is increased, and that it can occur even at recommended dosages.
Hyperalgesia and Allodynia Advise patients to inform their healthcare provider if they experience symptoms of hyperalgesia, including worsening pain, increased sensitivity to pain, or new pain [see Warnings and Precautions ( 5.7 ); Adverse Reactions ( 6.2 )] . Serotonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition called serotonin syndrome resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop after discharge from the hospital.
Instruct patients to inform their healthcare provider if they are taking or plan to take serotonergic medications [see Drug Interactions ( 7 )] . Constipation Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions ( 6 ), Clinical Pharmacology ( 12.2 )] .