oliceridine

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).

Adv. 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

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.

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)

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.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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

Therapeutic effects:

Decrease in severity of pain.

Classifications ⬆ ⬇

Therapeutic Classification: opioid analgesics

Pharmacologic Classification: opioid agonists

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Extensively distributed to extravascular tissues.

Metabolism/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.

Contr. Subst. Schedule ⬆ ⬇

Time/Action Profile ⬆ ⬇

(analgesia)

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

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of oliceridine to patient. Advise patient to read Medication Guideduring 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.

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Indications ⬇

Contraind./Precautions ⬆ ⬇