oliceridine

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

**REMS Drug**

Genetic Implications:

Pronunciation:
oh-li-ser-i-deen

Trade Name(s)

Olinvyk

Ther. Class.

opioid analgesics

Pharm. Class.

opioid agonists

Controlled Substance Schedule: II

Indications

Acute pain severe enough to require an IV opioid analgesic and for which alternative treatments are inadequate.

Action

Binds to mu-opioid receptors in the CNS. Alters the perception of and response to painful stimuli while producing generalized CNS depression.

Therapeutic Effect(s):

Decrease in severity of pain.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to extravascular tissues.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP3A4 and CYP2D6 isoenzymes into inactive metabolites. The CYP2D6 isoenzyme exhibits genetic polymorphism; ~7% of population may be poor metabolizers and may have significantly ↑ oliceridine concentrations and an ↑ risk of adverse effects. Primarily excreted in urine (70%) as metabolites (<10% excreted in urine as unchanged drug).

Half-life: 1.3–3 hr.

TIME/ACTION PROFILE (analgesia)

ROUTE	ONSET	PEAK	DURATION
IV	2–5 min	10–15 min	1–2 hr

Contraindication/Precautions

Contraindicated in:

Hypersensitivity;
Significant respiratory depression;
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment;
GI obstruction (including paralytic ileus);
Circulatory shock;
Impaired consciousness or coma.

Use Cautiously in:

Personal or family history of substance use disorder or mental illness;
Head trauma, brain tumor, or ↑ intracranial pressure;
Hypotension or volume depletion;
COPD, cor pulmonale, or pre-existing respiratory depression;
Adrenal insufficiency;
Biliary tract disease;
Acute pancreatitis;
Seizure disorder;
Severe hepatic impairment (use lowest starting dose and titrate slowly);
CYP2D6 poor metabolizers (↑ risk of respiratory depression) (may require less frequent dosing);
Concurrent use of strong or moderate CYP2D6 or CYP3A4 inhibitors (↑ risk of respiratory depression);
OB: Safety not established in pregnancy; other analgesics preferred during labor. Prolonged use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome;
Lactation: Safety not established in breastfeeding;
Rep: Men and women of reproductive potential (chronic use of opioids may ↓ fertility);
Pedi: Safety and effectiveness not established in children;
Geri: Older adults or debilitated patients (↑ risk of respiratory depression; use lowest starting dose and titrate slowly).

Adverse Reactions/Side Effects

CV: hypotension, QT interval prolongation (especially with cumulative doses >27 mg/day), tachycardia

Derm: pruritus, ↑ sweating, flushing, rash

Endo: ADRENAL INSUFFICIENCY

F and E: hypocalcemia, hypokalemia, hypomagnesemia, hypophosphatemia

GI: nausea, vomiting, ↑ amylase, diarrhea, dry mouth, dyspepsia, flatulence

Hemat: anemia

Local: extravasation

MS: back pain, muscle spasms

Neuro: constipation, dizziness, headache, sedation, anxiety, insomnia, restlessness

Resp: hypoxia, cough, dyspnea, RESPIRATORY DEPRESSION (including central sleep apnea and sleep-related hypoxemia)

Misc: allodynia, fever, opioid-induced hyperalgesia, physical dependence, psychological dependence, tolerance

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Strong CYP2D6 inhibitors and moderate CYP2D6 inhibitors, including bupropion, fluoxetine, paroxetine, and quinidine, may ↑ levels and risk of respiratory depression; if concurrent use necessary, administer oliceridine less frequently.
Strong CYP3A4 inhibitors and moderate CYP3A4 inhibitors, including clarithromycin, erythromycin, itraconazole, ketoconazole, and protease inhibitors, may ↑ levels and risk of respiratory depression; if concurrent use necessary, administer oliceridine less frequently.
Patients who are normal CYP2D6 metabolizers taking a CYP2D6 inhibitor and a strong CYP3A4 inhibitor may have ↑ levels and an ↑ risk of respiratory depression; if concurrent use necessary, administer oliceridine less frequently.
Patients who are poor CYP2D6 metabolizers taking a CYP3A4 inhibitor may have ↑ levels and an ↑ risk of respiratory depression; if concurrent use necessary, administer oliceridine less frequently.
CYP3A4 inducers, including carbamazepine, phenytoin, or rifampin, may ↓ levels and effectiveness.
Use with benzodiazepines or other CNS depressants, including other opioids, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol, trazodone, mirtazapine, 5-HT₃ receptor antagonists, linezolid, methylene blue, and triptans, ↑ risk of serotonin syndrome.
May ↓ the effects of diuretics ; may need to ↑ diuretic dose.
Phenothiazines or general anesthetics may ↑ risk of severe hypotension.
Mixed agonist/antagonist analgesics, including nalbuphine or butorphanol, and partial agonist analgesics, including buprenorphine, may ↓ oliceridine's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients.
Anticholinergic drugs may ↑ risk of urinary retention and/or constipation, which could lead to paralytic ileus.

Route/Dosage

IV (Adults): Intermittent bolus dosing: 1.5 mg initially; may then administer supplemental dose of 0.75 mg 1 hr after initial dose; may repeat supplemental dose of 0.75 mg no more frequently than hourly and titrated based on tolerability and response. Maximum single supplemental dose = 3 mg; maximum total cumulative daily dose = 27 mg. Patient-controlled analgesia (PCA) dosing: Initial dose (administered by health care professional) = 1.5 mg. Demand dose = 0.35–0.5 mg. Lockout interval = 6 min. Supplemental dose (administered by health care professional) = 0.75 mg may be administered beginning 1 hr after the initial dose and repeated hourly as needed (may be used in addition to the demand dose if needed for adequate analgesia). Maximum total cumulative daily dose = 27 mg.

Availability

Solution for injection: 1 mg/mL (for intermittent bolus dosing), 2 mg/2 mL (for intermittent bolus dosing), 30 mg/30 mL (for PCA only)

Assessment

Assess BP, HR, and respiratory rate before and periodically during administration, especially within the first 24–48 hr of therapy and following dose ↑. If respiratory rate <10/min, assess level of sedation. Dose may need to be ↓ by 25–50%. May cause orthostatic hypotension and syncope in ambulatory patients. Monitor for respiratory depression, especially during initiation or following dose ↑; serious, life-threatening, or fatal respiratory depression may occur. May cause sleep-related breathing disorders (central sleep apnea, sleep-related hypoxemia). Geri: Pedi: Assess geriatric and pediatric patients frequently; more sensitive to the effects of opioid analgesics and may experience side effects and respiratory complications more frequently.
Assess type, location, and intensity of pain prior to and 15 min following IV administration. Continually reevaluate patient to assess the maintenance of pain control, incidence of adverse reactions, and for the development of addiction, abuse, or misuse. Frequent communication is important among the prescriber, other members of the health care team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. If pain level ↑ after dose stabilization, attempt to identify the source of ↑ pain before ↑ oliceridine dose. If unacceptable opioid-related adverse reactions occur, consider ↓ the dose. Adjust dose to obtain an appropriate balance between pain management and opioid-related adverse reactions.
Oliceridine 1 mg is approximately equianalgesic with morphine 5 mg. An equianalgesic chart (see equianalgesic dosing guidelines) should be used when changing from one opioid to another.
Assess bowel function routinely. Institute prevention of constipation with ↑ intake of fluids and bulk and laxatives to minimize constipating effects. Administer stimulant laxatives routinely if opioid use exceeds 2–3 days, unless contraindicated. Consider drugs for opioid induced constipation.
Assess risk for opioid addiction, abuse, or misuse prior to administration.

Implementation

High Alert: Accidental overdose of opioid analgesics has resulted in fatalities. Before administering, check infusion pump settings.
Only administered by a health care professional. For IV administration only. Single doses >3 mg or use beyond 48 hr have not been evaluated. Cumulative daily dose should not exceed 27 mg.
Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
Explain therapeutic value of medication prior to administration to enhance the analgesic effect.
Regularly administered doses may be more effective than as needed administration. Analgesic is more effective if given before pain becomes severe.
Coadministration with nonopioid analgesics may have additive analgesic effects and permit lower opioid doses.
REMS: FDA strongly encourages health care professionals to complete a REMS-compliant education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain, available at www.fda.gov/OpioidAnalgesicREMSBlueprint. Information on programs can be found at 1-800-503-0784 or www.opioidanalgesicrems.com.
Discuss availability of naloxone for emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing therapy, especially if patient has household members (including children) or other close contacts at risk for accidental exposure or overdose. Consider prescribing naloxone, based on the patient's risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. However, the presence of risk factors for overdose should not prevent the proper management of pain in any patient.

To discontinue, taper dose gradually while monitoring carefully for signs and symptoms of withdrawal. If signs or symptoms of withdrawal (restlessness; lacrimation; rhinorrhea; yawning; perspiration; chills; myalgia; mydriasis; irritability; anxiety; backache; joint pain; weakness; abdominal cramps; insomnia; nausea; anorexia; vomiting; diarrhea; ↑ BP, respiratory rate, or HR) occur, ↑ the dose to the previous level and taper more slowly, either by ↑ the interval between dose ↓, ↓ the amount of change in dose, or both. Do not abruptly discontinue oliceridine in a physically dependent patient.

IV Administration

IV Push: 1 mg/mL and 2 mg/2 mL vials are used for intermittent IV push. 30 mg/30 mL vial is for patient-controlled analgesic (PCA) (see Route and Dosage). Solution is clear and colorless; do not administer solutions that are cloudy, discolored, or contain particulate matter.

Patient/Family Teaching

Explain purpose and side effects of oliceridine to patient. Advise patient to read Medication Guide during therapy.
REMS: Instruct patient on how and when to ask for pain medication. Do not stop taking without discussing with health care professional; may cause withdrawal symptoms if discontinued abruptly after prolonged use. The Patient Counseling Guide (PCG) is available at www.fda.gov/OpioidAnalgesicREMSPCG.
May cause drowsiness or dizziness. Advise patient to call for assistance when ambulating and to avoid driving or other activities that require alertness until response to the medication is known.
Advise patient to notify health care professional if pain control is not adequate or if side effects occur.
Advise patient to change positions slowly to minimize orthostatic hypotension.
Instruct patient to avoid concurrent use of alcohol or other CNS depressants.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
Rep: Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal symptoms (irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, failure to gain weight); usually occur the first days after birth.

Evaluation/Desired Outcomes

Decrease in severity of pain without a significant alteration in level of consciousness or respiratory status.