OxyCODONE

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as hydrochloride:

Generic: 5 mg

Capsule ER 12 Hour Abuse-Deterrent, Oral:

Xtampza ER: 9 mg (100 ea); 13.5 mg (100 ea); 18 mg (100 ea); 27 mg (100 ea); 36 mg (100 ea)

Concentrate, Oral, as hydrochloride:

Generic: 100 mg/5 mL (15 mL [DSC], 30 mL)

Solution, Oral, as hydrochloride:

Generic: 5 mg/5 mL (5 mL, 15 mL, 473 mL, 500 mL)

Tablet, Oral, as hydrochloride:

Roxicodone: 5 mg [scored]

Roxicodone: 15 mg [scored; contains fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow)]

Roxicodone: 30 mg [scored]

Generic: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg

Tablet Abuse-Deterrent, Oral, as hydrochloride:

Oxaydo: 5 mg, 7.5 mg

Tablet ER 12 Hour Abuse-Deterrent, Oral, as hydrochloride:

OxyCONTIN: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg

OxyCONTIN: 80 mg [contains fd&c blue #2 aluminum lake]

Generic: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg

Pharmacology

Mechanism of Action

Binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: Children 2 to 10 years: 2.1 L/kg (range: 1.2 to 3.7 L/kg); Adults: 2.6 L/kg; distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain

Metabolism

Hepatically via CYP3A4 to noroxycodone (has weak analgesic), noroxymorphone, and alpha- and beta-noroxycodol. CYP2D6 mediated metabolism produces oxymorphone (has analgesic activity; low plasma concentrations [<15%]), alpha- and beta-oxymorphol.

Excretion

Urine (~19% as parent; >64% as metabolites)

Onset of Action

Pain relief: Immediate release: 10 to 15 minutes; Peak effect: Immediate release: 0.5 to 1 hour

Time to Peak

Plasma: Immediate release: 1.2 to 1.9 hours; Extended release: 4 to 5 hours

Duration of Action

Immediate release: 3 to 6 hours; Extended release: ≤12 hours

Half-Life Elimination

Apparent: Immediate release: 3.2 to ~4 hours; Extended release tablet: 4.5 hours; Extended release capsule: 5.6 hours

Elimination: Children 2 to 10 years: 1.8 hours (range: 1.2 to 3 hours); Adults: 3.7 hours

Adults with CrCl <60 mL/minute: Half-life increases by 1 hour, but peak oxycodone concentrations increase by 50% and AUC increases by 60%

Adults with mild to moderate hepatic impairment: Half-life increases by 2.3 hours, peak oxycodone concentrations increase by 50%, and AUC increases by 95%

Protein Binding

38% to 45%

Use in Specific Populations

Special Populations: Renal Function Impairment

Higher peak plasma oxycodone (50%), and noroxycodone (20%), higher AUC for oxycodone (60%), noroxycodone (50%), and oxymorphone (40%) in patients with CrCl <60 mL/minute. There is an increased half-life elimination for oxycodone elimination of only 1 hour.

Special Populations: Hepatic Function Impairment

Peak plasma oxycodone and noroxycodone concentrations 50% and 20% higher; AUC values are 95% and 65% higher, respectively, in mild to moderate hepatic impairment. Oxymorphone peak plasma concentration and AUC values are lower by 30% and 40%. The half-life elimination for oxycodone is increased by 2.3 hours.

Use: Labeled Indications

Pain management:

Immediate-release formulations: Management of acute or chronic moderate to severe pain where the use of an opioid analgesic is appropriate and for which alternative treatments are inadequate.

Extended-release formulations:

Capsules: Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate in adults

Tablets: Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate in adults and opioid-tolerant pediatric patients ≥11 years of age who are already receiving and tolerating a minimum daily opioid dose of at least 20 mg oxycodone orally or its equivalent.

Limitations of use: Reserve oxycodone for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Oxycodone ER is not indicated as an as-needed analgesic.

Contraindications

Hypersensitivity (eg, anaphylaxis, angioedema) to oxycodone or any component of the formulation; significant respiratory depression; hypercapnia; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; GI obstruction, including paralytic ileus (known or suspected).

Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other opioids; suspected surgical abdomen (eg, acute appendicitis or pancreatitis); any disease/condition that affects bowel transit; mild pain that can be managed with other pain medications (immediate release, suppository); mild, intermittent or short duration pain that can be managed with other pain medications or acute pain (extended release); chronic obstructive airway; status asthmaticus; cor pulmonale; acute alcoholism; delirium tremens; convulsive disorders; severe CNS depression; increased cerebrospinal or intracranial pressure; head injury; monoamine oxidase (MAO) inhibitors (concomitant use or within 14 days of therapy); pregnant women or during labor and delivery; breastfeeding.

Dosage and Administration

Dosing: Adult

Pain management: Note: All doses should be titrated to appropriate effect.

Immediate release:

Oral: Initial: 5 to 15 mg every 4 to 6 hours as needed; dosing range: 5 to 20 mg per dose (APS 2008). For severe chronic pain, administer on a regularly scheduled basis, every 4 to 6 hours, at the lowest dose that will achieve adequate analgesia.

Rectal [Canadian product]: Initial: One suppository 3 to 4 times daily as needed.

Extended release: Oral:

Note: Oxycodone ER capsules are not bioequivalent to ER tablets. Dose of ER capsules is expressed as oxycodone base and the dose of ER tablets is expressed as oxycodone hydrochloride. Oxycodone ER 60 mg and 80 mg tablets are intended for use in opioid-tolerant patients only. Single doses >40 mg (ER tablets) or >36 mg (ER capsules), or a total dose of >80 mg daily (ER tablets) or >72 mg daily (ER capsules) are for use only in opioid-tolerant patients. Opioid tolerance is defined as: Patients already taking at least morphine 60 mg orally daily, oxymorphone 25 mg orally daily, transdermal fentanyl 25 mcg per hour, oxycodone 30 mg orally daily, hydromorphone 8 mg orally daily, hydrocodone 60 mg orally daily or an equivalent dose of another opioid for at least 1 week.

Opioid naive (use as the first opioid analgesic or use in patients who are not opioid tolerant): Initial:

ER tablet: 10 mg every 12 hours

ER capsules: 9 mg every 12 hours

Conversion from other oral oxycodone formulations to oxycodone ER: Initiate oxycodone ER with 50% of the total daily oral oxycodone daily dose (mg/day) administered every 12 hours.

Conversion from other opioids to oxycodone ER: Discontinue all other around-the-clock opioids when oxycodone ER is initiated. Initiate with 10 mg (ER tablets) or 9 mg (ER capsules) every 12 hours. Substantial interpatient variability exists due to patient specific factors, relative potency of different opioids, and dosage forms; therefore, it is preferable to underestimate the initial 24 hour oral oxycodone requirements and utilize rescue medication (immediate-release opioid).

Conversion from transdermal fentanyl patch to oxycodone ER: Note: Remove fentanyl patch at least 18 hours prior to starting oxycodone ER. The manufacturer suggests using the conservative conversion factor of oxycodone ER tablets 10 mg or oxycodone ER capsules 9 mg every 12 hours for each fentanyl 25 mcg/hour transdermal patch; systematic assessment of this suggested conversion has not been completed; monitor patients closely.

Conversion from methadone to oxycodone ER: Close monitoring is required when converting methadone to another opioid. Ratio between methadone and other opioid agonists varies widely according to previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

Maintenance dose: Dosage adjustment (titration): After initiation of oxycodone ER, adjust dose in increments (25% to 50%) no more frequently than every 1 to 2 days until desired pain control. Recommended maximum dose of ER capsules is 288 mg/day. Patients may require rescue doses of an immediate-release analgesic during dose titration. Observe for signs and symptoms of opioid withdrawal or signs of over sedation/toxicity; if unacceptable adverse reactions occur, the subsequent dose may be reduced. Note: Some clinicians have reported that in certain chronic pain patients, more frequent dosing (ie, every 8 hours) is required for effective pain relief (Gallagher 2007; Marcus 2004; Nicholson 2006), although dosing more frequently than every 12 hours is not recommended by the manufacturer, and safety and efficacy has not been established.

Dosage adjustment for concomitant therapy: Concomitant CNS depressants: Initiate oxycodone ER with 33% to 50% of the calculated recommended dose. If reduced dose is less than smallest available dosage form consider alternative analgesic.

Discontinuation of therapy: When discontinuing chronic opioid therapy, the dose should be gradually tapered down. An optimal universal tapering schedule for all patients has not been established (CDC [Dowell 2016]). Proposed schedules range from slow (eg, 10% reductions per week) to rapid (eg, 25% to 50% reduction every few days) (CDC 2015). Tapering schedules should be individualized to minimize opioid withdrawal while considering patient-specific goals and concerns as well as the pharmacokinetics of the opioid being tapered. An even slower taper may be appropriate in patients who have been receiving opioids for a long duration (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse events (CDC [Dowell 2016]). Monitor carefully for signs/symptoms of withdrawal. If the patient displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing amount of daily dose reduction, pausing the taper and restarting when the patient is ready, and/or coadministration of an alpha-2 agonist (eg, clonidine) to blunt withdrawal symptoms (Berna 2015; CDC [Dowell 2016]). Continue to offer nonopioid analgesics as needed for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms (eg, GI complaints, muscle spasm) as needed (Berna 2015; Sevarino 2018).

Dosage adjustment in debilitated patients (nonopioid tolerant):

Immediate release: Oral, rectal [Canadian product]: Initial: There are no specific dosage adjustments provided in the manufacturer's labeling; use caution and with a reduced dose.

Extended release: Oral: Initial: Initiate oxycodone ER with 33% to 50% of the calculated recommended dose. If reduced dose is less than smallest available dosage form, consider alternative analgesic.

Dosing: Geriatric

Refer to adult dosing. Initiate therapy at low end of dosing range and use caution.

Dosing: Pediatric

Note: Doses should be titrated to appropriate effect. Multiple concentrations of oral solution available (20 mg/mL and 1 mg/mL); the highly concentrated formulation (20 mg/mL) should only be used in opioid tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week). Orders for oxycodone oral solutions (20 mg/mL or 1 mg/mL) should be clearly written to include the intended dose (in mg not mL) and the intended product concentration to be dispensed to avoid potential dosing errors:

Analgesia, moderate to severe pain: Immediate release:

Infants ≤6 months: Limited data available: Oral: Initial dose: 0.025 to 0.05 mg/kg/dose every 4 to 6 hours as needed (Berde 2002)

Infants >6 months, Children, and Adolescents: Oral:

Patient weight <50 kg: Initial dose: 0.1 to 0.2 mg/kg/dose every 4 to 6 hours as needed; for severe pain some experts have recommended an initial dose of 0.2 mg/kg; usual maximum dose range: 5 to 10 mg (American Pain Society 2008; APA 2012; Berde 2002)

Patient weight ≥50 kg: Initial dose: 5 to 10 mg every 4 to 6 hours as needed; for severe pain an initial dose of 10 mg may be used; usual maximum dose: 20 mg/dose (American Pain Society 2008; Berde 2002)

Analgesia, severe pain requiring around-the-clock long-term opioid therapy: Extended release tablets (eg, OxyContin): Note: Use only in pediatric patients ≥11 years of age who are already receiving opioid therapy for at least 5 consecutive days, tolerating a minimum daily opioid dose of at least 20 mg of oxycodone orally or its equivalent at least for the 2 days immediately prior to starting extended release oxycodone tablets, and for which alternative treatment options are inadequate. Prior to initiation, all other around-the-clock opioid therapy must be discontinued.

Initial dose: Children ≥11 years and Adolescents: Oral: Initial dose based on current opioid regimen dose; use the following conversion factor table and equation to convert the current opioid(s) daily dose to the extended release oxycodone tablet daily dose. Note: Substantial interpatient variability exists due to patient specific factors, relative potency of different opioids, and dosage forms; therefore, it is preferable to underestimate the initial 24-hour oral oxycodone requirements and utilize rescue medication (immediate release opioid):

Initial dose of extended release oxycodone tablets administered every 12 hours = (mg/day of current opioid regimen X conversion factor)/2

Dose calculations or adjustments for specific clinical scenarios:

• If rounding is necessary, numerical value should be rounded down to the nearest tablet strength. If calculated daily dose is <20 mg, do not start extended release oxycodone tablet as there is no safe tablet strength available.
• If more than one opioid in the regimen, calculate the approximate extended release oxycodone tablet dose for each opioid and sum the totals for the approximate total daily extended release oxycodone tablet dose, then divide by 2 for the 12-hour extended release oxycodone dose.
• If current opioid regimen includes a fixed-dose opioid/nonopioid dosage form (eg, hydrocodone/acetaminophen), only the mg of opioid should be used in the conversion calculations.
• If patient receiving concomitant CNS depressants, reduce extended release oxycodone tablet starting dose by ¹/₃ to ¹/₂ the calculated initial dose.
• If asymmetric dosing, the higher dose should be scheduled as the morning dose, and the lower dose 12 hours later.

Note: The following conversion table should ONLY be used to convert opioid doses to extended release oxycodone tablet (not from extended release oxycodone tablet to other opioids; it is NOT a table of equianalgesic doses as it may overestimate initial dose).

Table has been converted to the following text:

Conversion Factor for Calculating Initial Extended Release Oxycodone Tablet Dose in Pediatric Patients ≥11 years

Current opioid regimen to be converted to extended release oxycodone tablet: Oxycodone: Oral: Conversion factor = 1

Current opioid regimen to be converted to extended release oxycodone tablet: Hydrocodone: Oral: Conversion factor = 0.9

Current opioid regimen to be converted to extended release oxycodone tablet: Hydromorphone: Oral: Conversion factor = 4; Parenteral*: Conversion factor = 20

Current opioid regimen to be converted to extended release oxycodone tablet: Morphine: Oral: Conversion factor = 0.5; Parenteral*: Conversion factor = 3

Current opioid regimen to be converted to extended release oxycodone tablet: Tramadol: Oral: Conversion factor = 0.17; Parenteral*: Conversion factor = 0.2

*For patients receiving high-dose parenteral opioids, a more conservative conversion factor should be applied (ie, lower numerical conversion factor); for example, for high-dose parenteral morphine, a conversion of 1.5 should be used for calculations instead of 3.

Conversion from fentanyl patch to extended release oxycodone tablet: Limited data available: Children ≥11 years and Adolescents: Note: Remove fentanyl patch at least 18 hours prior to starting extended release oxycodone. Initial dose based on current opioid regimen dose; the manufacturer suggests using the conservative conversion factor of 10 mg every 12 hours of extended release oxycodone tablet for each 25 mcg/hour fentanyl transdermal patch; systemic assessment of this suggested conversion has not been completed, monitor patients closely

Maintenance dose: Dosage adjustment (titration): After initiation of extended release oxycodone tablet, adjust dose in small increments (up to 25% of current total daily dosage) no more frequently than every 1 to 2 days until desired pain control; patients may require rescue doses of an immediate release analgesic during dose titration. Observe for signs and symptoms of opioid withdrawal or signs of oversedation/toxicity; if unacceptable adverse reactions occur, the subsequent dose may be reduced.

Administration

Appropriate laxatives should be administered to avoid the constipating side effects associated with use. Antiemetics may be needed for persistent nausea. Some dosage forms may not be appropriate for administration through feeding tubes (eg, gastric, NG). Refer to product labeling.

Extended release dosage forms:

Tablet: Administer with or without food. Swallow tablet whole. Do not moisten, dissolve, cut, crush, break, or chew extended release tablets. Extended release tablets should be administered one at a time and each followed with water immediately after placing in the mouth.

Capsule: Administer each dose with food and approximately the same amount. For patients with difficulty swallowing, capsule may be opened and the contents sprinkled on soft foods (eg, applesauce, pudding, yogurt, ice cream, jam) or into a cup for administration directly into the mouth. Rinse mouth immediately afterwards to ensure all contents have been swallowed. Contents of capsule may also be administered through a nasogastric (NG) tube or gastrostomy tube (G-tube). Flush tube with water first, then pour capsule contents directly into tube (do not premix capsule contents with fluid that will be used to flush them through the tube). After contents have been placed in tube, flush tube with 15 mL of water, milk, or liquid nutritional supplement once and then repeat twice with 10 mL.

Immediate release dosage forms:

Capsule: Administer with or without food.

Oral solution: Administer with or without food. Available in two strengths; 1 mg/mL and a concentrated oral solution (20 mg/mL). Precautions should be taken to avoid confusion between the different concentrations; prescriptions should have the concentration specified as well as the dose clearly represented as milligram (mg) of oxycodone, not volume (mL). The enclosed calibrated oral syringe should always be used to administer the concentrated oral solution to ensure the dose is measured and administered accurately. The concentrated oral solution (20 mg/mL) should only be used in opioid-tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week).

Tablets:

Without abuse deterrent: Administer with or without food. When administered with food, onset may be delayed.

With abuse deterrent:

Oxaydo: Administer with or without food. Do not crush, chew, or dissolve the tablets. Due to inactive ingredient that causes nasal burning (upon snorting) and throat irritation, the tablet must be swallowed whole with enough water to ensure complete swallowing immediately after placing in the mouth. The tablet should not be wet prior to placing in the mouth.

Suppository [Canadian product]: Administer rectally. Do not break, crush, cut, or dissolve the suppositories.

Dietary Considerations

Instruct patient to avoid high-fat meals when taking some products (food has no effect on the reformulated OxyContin).

Storage

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from light and moisture.

Suppository [Canadian product]: Store below 25°C (77°F).

Drug Interactions

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Alvimopan: Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Consider therapy modification

Amphetamines: May enhance the analgesic effect of Opioid Agonists. Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Monitor therapy

CYP3A4 Inhibitors (Strong): May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Desmopressin: Opioid Agonists may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Eluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline. Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Gastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Consider therapy modification

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Monoamine Oxidase Inhibitors: OxyCODONE may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Avoid combination

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of nalmefene and opioid agonists. Discontinue nalmefene 1 week prior to any anticipated use of opioid agonistss. If combined, larger doses of opioid agonists will likely be required. Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Opioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Pegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

PHENobarbital: May enhance the CNS depressant effect of OxyCODONE. PHENobarbital may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Primidone: May enhance the CNS depressant effect of OxyCODONE. Primidone may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Consider therapy modification

Ramosetron: Opioid Agonists may enhance the constipating effect of Ramosetron. Monitor therapy

RifAMPin: May decrease the serum concentration of OxyCODONE. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonergic Agents (High Risk): Opioid Agonists may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Consider therapy modification

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

St John's Wort: May decrease the serum concentration of OxyCODONE. Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Voriconazole: May enhance the adverse/toxic effect of OxyCODONE. Voriconazole may increase the serum concentration of OxyCODONE. Management: A reduced oxycodone dose may be necessary with concurrent voriconazole. Increased frequency and duration of monitoring for oxycodone-related adverse effects is recommended. Consider therapy modification

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Test Interactions

Some quinolones may produce a false-positive urine screening result for opioids using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opioid screens by more specific methods should be considered.

Adverse Reactions

As reported with adult patients, unless otherwise noted.

>10%:

Central nervous system: Drowsiness (extended-release: 9% to 23%, extended-release, adolescents: 1% to <5%; immediate-release: ≥3%), headache (extended-release: 14%; immediate-release: ≥3%), dizziness (extended-release: 2% to 13%; immediate-release: ≥3%)

Dermatologic: Pruritus (extended-release: 3% to 13%; immediate-release: ≥3%)

Gastrointestinal: Nausea (extended-release: 11% to 23%; immediate-release: ≥3%), constipation (extended-release: 5% to 23%; extended-release, adolescents: 9%; immediate-release: ≥3%), vomiting (extended-release: 4% to 21%; immediate-release: 3%)

Miscellaneous: Fever (extended-release: 1% to 11%; immediate-release: ≥3%)

1% to 10%:

Cardiovascular: Flushing (extended-release: 1% to 5%), hypertension (extended-release: 1% to 5%), orthostatic hypotension (extended-release: 1% to 5%), oxygen saturation decreased (extended-release, adolescents: 1% to <5%), edema (immediate-release: ≤5%; extended-release: <1%), tachycardia (<5%), cardiac failure (immediate-release: <3%), deep vein thrombosis (immediate-release: <3%), hypotension (<3%), palpitations (<3%; may occur with withdrawal), peripheral edema (immediate-release: <3%; extended-release: <1%), thrombophlebitis (immediate-release: <3%), vasodilation (<3%)

Central nervous system: Abnormality in thinking (extended-release: 1% to 5%), dysphoria (extended-release: 1% to 5%), insomnia (1% to 5%), irritability (extended-release: 1% to 5%), twitching (extended-release: 1% to 5%), abnormal dreams (extended-release: ≤5%), anxiety (≤5%), chills (≤5%), confusion (≤5%), euphoria (extended-release: ≤5%), fatigue (extended-release: ≤5%), hypoesthesia (≤5%), migraine (≤5%), nervousness (≤5%), withdrawal syndrome (extended-release: ≤5%), agitation (<5%), pain (<5%), depression (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), lethargy (adolescents: 1% to <5%; extended-release, adults: <1%), paresthesia (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), procedural pain (extended-release, adolescents: 1% to <5%), hypertonia (<3%), neuralgia (<3%), personality disorder (immediate-release: <3%)

Dermatologic: Excoriation (extended-release: 1% to 5%), diaphoresis (≤5%), hyperhidrosis (≤5%), skin rash (≤5%), skin photosensitivity (immediate-release: <3%), urticaria (<3%)

Endocrine & metabolic: Hypochloremia (extended-release, adolescents: 1% to <5%), hyponatremia (extended-release: 1% to <5%), weight loss (extended-release, adolescents: 1% to <5%), hyperglycemia (≤5%), gout (immediate-release: <3%)

Gastrointestinal: Diarrhea (≤6%), xerostomia (≤6%), gastritis (extended-release: 1% to 5%), hiccups (extended-release: 1% to 5%), upper abdominal pain (extended-release: 1% to 5%), abdominal pain (≤5%), anorexia (≤5%), decreased appetite (≤5%), dyspepsia (≤5%), gastroesophageal reflux disease (extended-release: ≤5%), dysphagia (immediate-release: <3%; extended-release: <1%), gingivitis (immediate-release: <3%), glossitis (immediate-release: <3%)

Genitourinary: Dysuria (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), urinary retention (extended-release, adolescents: 1% to <5%; extended-release, adults: <1%), urinary tract infection (immediate-release: <3%)

Hematologic & oncologic: Decreased hemoglobin (extended-release, adolescents: 1% to <5%), decreased platelet count (extended-release, adolescents: 1% to <5%), decreased red blood cells (extended-release, adolescents: 1% to <5%), febrile neutropenia (extended-release, adolescents: 1% to <5%), neutropenia (extended-release, adolescents: 1% to <5%), anemia (immediate-release: <3%), hemorrhage (immediate-release: <3%), iron deficiency anemia (immediate-release: <3%), leukopenia (immediate-release: <3%)

Hepatic: Increased serum alanine aminotransferase (extended-release, adolescents: 1% to <5%)

Hypersensitivity: Hypersensitivity reaction (<3%)

Infection: Herpes simplex infection (immediate-release: <3%), infection (immediate-release: <3%), sepsis (immediate-release: <3%)

Neuromuscular & skeletal: Asthenia (1% to 6%), limb pain (extended-release, adolescents: 1% to <5%), arthralgia (≤5%), back pain (≤5%), musculoskeletal pain (extended release: ≤5%), myalgia (≤5%), tremor (≤5%), arthritis (immediate-release: <3%), laryngospasm (immediate-release: <3%), neck pain (immediate-release: <3%), ostealgia (immediate-release: <3%), pathological fracture (immediate-release: <3%)

Ophthalmic: Blurred vision (extended-release: 1% to 5%), amblyopia (immediate-release: <3%)

Respiratory: Cough (≤5%), dyspnea (≤5%), oropharyngeal pain (extended-release: ≤5%), bronchitis (immediate-release: <3%), epistaxis (immediate-release: <3%), flu-like symptoms (immediate-release: <3%), laryngismus (immediate-release: <3%), pharyngitis (immediate-release: <3%), pulmonary disease (immediate-release: <3%), rhinitis (immediate-release: <3%), sinusitis (immediate-release: <3%)

Miscellaneous: Seroma (extended-release, adolescents: 1% to <5%), accidental injury (<3%; extended-release: <1%)

Frequency not defined:

Cardiovascular: Circulatory depression, shock

Central nervous system: Depersonalization

Respiratory: Respiratory depression

<1%, postmarketing, and/or case reports: Abnormal gait, aggressive behavior, amenorrhea, amnesia, chest pain, choking sensation, cholestasis, dehydration, dental caries, depression of ST segment on ECG, diverticulitis of the gastrointestinal tract (exacerbation), drug abuse, drug dependence, drug overdose (may be intentional), dysgeusia, emotional lability, eructation, exfoliative dermatitis, facial edema, flatulence, gag reflex, gastrointestinal disease, hallucination, hematuria, hyperalgesia, hyperkinesia, hypogonadism, hypotonia, impotence, increased appetite, increased gamma-glutamyl transferase, increased heart rate, increased liver enzymes, increased thirst, intestinal obstruction, lymphadenopathy, malaise, memory impairment, mood changes, neonatal withdrawal, night sweats, pharyngeal edema, polyuria, restlessness, seizure, SIADH, sleep disturbance, speech disturbance, stomatitis, stupor, suicidal ideation, suicidal tendencies, syncope, tinnitus, vertigo, visual disturbance, voice disorder, xeroderma

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, that may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Constipation: May cause constipation, which may be problematic in patients with unstable angina and patients post-myocardial infarction (MI). Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.
• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.
• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxymorphone).
• Respiratory depression: [US Boxed Warning]: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Swallow ER tablets whole; crushing, chewing, or dissolving can cause rapid release and a potentially fatal dose. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Adrenocortical insufficiency: Use with caution in patients with adrenocortical insufficiency, including Addison disease; dose adjustment may be required. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan 2013).
• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi.
• CNS depression/coma: Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO₂ retention.
• Delirium tremens: Use with caution in patients with delirium tremens.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.
• Hepatic impairment: Use with caution in patients with hepatic impairment; oxycodone clearance may decrease.
• Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]).
• Obesity: Use with caution in patients who are morbidly obese.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture; dose adjustment may be required.
• Psychosis: Use with caution in patients with toxic psychosis.
• Renal impairment: Use with caution in patients with renal impairment; oxycodone clearance may decrease.
• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.
• Seizures: Use with caution in patients with a history of seizure disorders; may cause or exacerbate preexisting seizures.
• Sleep-related disorders: Opioid use increases the risk for sleep-related disorders (eg, central sleep apnea [CSA], hypoxemia) in a dose-dependent fashion. Use with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing (eg, heart failure, obesity). Consider dose reduction in patients presenting with CSA. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]).
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Benzodiazepines or other CNS depressants: [US Boxed Warning]: 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 of oxycodone and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosage and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.
• CYP 3A4 interactions: [US Boxed Warning]: Use with all CYP3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitant CYP 3A4 inducer may result in increased oxycodone concentrations. Monitor patients receiving oxycodone and any CYP 3A4 inhibitor or inducer.
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Dose reduction may be required. Consider the use of alternative nonopioid analgesics in these patients.
• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Use opioids for chronic pain with caution in this age group; monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]). Consider the use of alternative nonopioid analgesics in these patients.
• Neonates: Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated 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. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein-binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Extended-release tablets: Tablets may be difficult to swallow and could become lodged in throat; patients with swallowing difficulties may be at increased risk. Cases of intestinal obstruction or diverticulitis exacerbation have also been reported, including cases requiring medical intervention to remove the tablet; patients with an underlying GI disease (eg, esophageal cancer, colon cancer) may be at increased risk.
• Oral solutions: [US Boxed Warning]: Ensure accuracy when prescribing, dispensing, and administering oxycodone oral solution. Dosing errors due to confusion between mg and mL, and other oxycodone oral solutions of different concentrations can result in accidental overdose.

Other warnings/precautions:

• Abrupt discontinuation/withdrawal: Abrupt discontinuation in patients who are physically dependent on opioids has been associated with serious withdrawal symptoms, uncontrolled pain, attempts to find other opioids (including illicit), and suicide. Use a collaborative, patient-specific taper schedule that minimizes the risk of withdrawal, considering factors such as current opioid dose, duration of use, type of pain, and physical and psychological factors. Monitor pain control, withdrawal symptoms, mood changes, suicidal ideation, and for use of other substances and provide care as needed. Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may also precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists.
• Abuse/misuse/diversion: [US Boxed Warning]: Use exposes patients and other users to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient's risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk for misuse include younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]).
• Accidental exposure: [US Boxed Warning]: Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of oxycodone.
• Appropriate use: Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, certain anticonvulsants and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and non-opioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using immediate-release opioids (instead of extended-release/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 morphine milligram equivalents (MME)/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]).
• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.
• REMS program: [US Boxed Warning]: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, a REMS is required. Drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist; and consider other tools to improve patient, household, and community safety.
• Surgery: Opioids decrease bowel motility; monitor for decreased bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.

Monitoring Parameters

Pain relief, respiratory and mental status, blood pressure; bowel function; signs/symptoms of misuse, abuse, and addiction; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013)

Alternate recommendations: Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. Re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and re-checking should be considered at least yearly (includes controlled prescription medications and illicit drugs of abuse). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (Dowell [CDC 2016]).

Pregnancy

Pregnancy Considerations

Oxycodone crosses the placenta (Kokki 2012).

According to some studies, maternal use of opioids may be associated with birth defects (including neural tube defects, congenital heart defects, and gastroschisis), poor fetal growth, stillbirth, and preterm delivery (CDC [Dowell 2016]).

[US Boxed Warning]: Prolonged use of oxycodone 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. If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur (Chou 2009). Symptoms of neonatal abstinence syndrome (NAS) following opioid exposure may be autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high-pitched crying, hyperactivity, increased muscle tone, increased wakefulness/abnormal sleep pattern, irritability, sneezing, seizure, tremor, yawning) (Dow 2012; Hudak 2012). Mothers who are physically dependent on opioids may give birth to infants who are also physically dependent. Opioids may cause respiratory depression and psycho-physiologic effects in the neonate; newborns of mothers receiving opioids during labor should be monitored.

Oxycodone is not commonly used to treat pain during labor and immediately postpartum (ACOG 209 2019) or chronic noncancer pain in pregnant women or those who may become pregnant (CDC [Dowell 2016]; Chou 2009).

Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility in men and women (Brennan 2013).

Patient Education

What is this drug used for?

• It is used to ease pain.

Frequently reported side effects of this drug

• Weakness
• Nausea
• Vomiting
• Headache
• Trouble sleeping
• Itching
• Lack of appetite
• Diarrhea
• Dry mouth

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe dizziness
• Passing out
• Confusion
• Severe constipation
• Severe abdominal pain
• Difficulty breathing
• Slow breathing
• Shallow breathing
• Difficult urination
• Fast heartbeat
• Slow heartbeat
• Abnormal heartbeat
• Seizures
• Tremors
• Vision changes
• Chest pain
• Sensing things that seem real but are not
• Mood changes
• Trouble with memory
• Abnormal gait
• Difficulty speaking
• Swelling of arms or legs
• Severe fatigue
• Sexual dysfunction (males)
• Decreased sex drive
• No menstrual periods
• Trouble getting pregnant
• Serotonin syndrome like dizziness, severe headache, agitation, sensing things that seem real but are not, fast heartbeat, abnormal heartbeat, flushing, tremors, sweating a lot, change in balance, severe nausea, or severe diarrhea.
• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss.
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.