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Oxycodone: Drug information

Oxycodone: Drug information
(For additional information see "Oxycodone: Patient drug information" and see "Oxycodone: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Addiction, abuse, and misuse:

Oxycodone 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 oxycodone and monitor all patients regularly for the development of these behaviors or conditions.

Opioid analgesic risk evaluation and mitigation strategy (REMS)

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the FDA has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are strongly encouraged to complete a REMS-compliant education program and 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.

Life-threatening respiratory depression:

Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone. Monitor for respiratory depression, especially during initiation of oxycodone or following a dose increase. Instruct patients to swallow oxycodone tablets whole; crushing, chewing, or dissolving oxycodone ER tablets can cause rapid release and absorption of a potentially fatal dose of oxycodone.

Accidental ingestion:

Accidental ingestion of even one dose of oxycodone, especially by children, can result in a fatal overdose of oxycodone.

Neonatal opioid withdrawal:

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.

Cytochrome P450 3A4 interaction:

The concomitant use of oxycodone with all cytochrome P450 (CYP-450) 3A4 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 concomitantly used CYP3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving oxycodone and any CYP3A4 inhibitor or inducer.

Risks from concomitant use with benzodiazepines or other CNS depressants:

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 dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Risk of medication errors (oral solution):

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.

Brand Names: US
  • Oxaydo;
  • OxyCONTIN;
  • Roxicodone;
  • RoxyBond;
  • Xtampza ER
Brand Names: Canada
  • ACT Oxycodone CR [DSC];
  • APO-Oxycodone CR;
  • Oxy-IR;
  • OxyNEO;
  • PMS-OxyCODONE;
  • PMS-OxyCODONE CR;
  • Supeudol;
  • Supeudol 10;
  • Supeudol 20
Pharmacologic Category
  • Analgesic, Opioid
Dosing: Adult

Note: Place in therapy: When used for managing moderate to severe pain, opioids may be part of a comprehensive, multimodal, patient-specific treatment plan for pain. Maximize nonopioid analgesia, if appropriate, prior to initiation of opioid analgesia (Ref). Dose selection: Dosing provided is based on typical doses and some patients may require higher or lower doses. Individualize dosing and dosing intervals based on patient-specific factors (eg, comorbidities, severity of pain, concomitant medications, cachexia, general condition, degree of opioid experience/tolerance) and titrate to patient-specific treatment goals (eg, improvement in function and quality of life, decrease in pain using a validated pain rating scale). Use the lowest effective dose for the shortest period of time. Safety: Consider prescribing naloxone for 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 [MME]/day orally [equivalent to ≥33 mg oxycodone/day]), and/or concomitant benzodiazepine use (Ref).

Acute pain in opioid-naive patients

Acute pain in opioid-naive patients:

General dosing: Note: For acute non–cancer-related pain severe enough to require an opioid, utilize multimodal pain control, maximize nonopioid analgesics, and limit the quantity prescribed to the expected duration of acute pain; a quantity sufficient for ≤3 days is often adequate, whereas >7 days is rarely needed. Do not use long-acting preparations for treatment of acute pain (Ref).

Immediate release:

Oral: Initial: 5 mg every 4 to 6 hours as needed; adjust dose according to patient response. Usual dosage range: 5 to 15 mg every 4 to 6 hours as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. For outpatient use, usually up to 20 mg/day for moderate pain or up to 30 mg/day for severe pain will suffice. Dosing is based on severity of pain and patient-specific factors; reduced dosing may be indicated in patients with comorbidities (Ref).

Rectal [Canadian product]: Usual dosage range: One (10 or 20 mg) suppository up to 3 to 4 times daily as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies (Ref).

Acute pain in patients on chronic opioid therapy

Acute pain (eg, breakthrough cancer pain) in patients on chronic opioid therapy:

Immediate release: Oral: Usual dose: In conjunction with the scheduled opioid, administer 5% to 15% (rarely up to 20%) of the 24-hour oxycodone requirement (or MME) as needed using an IR formulation every 4 to 6 hours with subsequent dosage adjustments based upon response (Ref). Note: If chronic opioid is not oxycodone, use MME calculations cautiously due to lack of complete cross-tolerance; generally, reduce calculated dose by 25% to 50%; conversions from methadone are highly variable and require extreme caution (Ref).

Acute postoperative pain, postoperative recovery/postanesthesia care unit

Acute postoperative pain, postoperative recovery/postanesthesia care unit :

Note: Optimize multimodal perioperative pain management (eg, regional or local anesthesia, nerve blocks, nonopioid analgesics, other adjuvants) to minimize opioid use (Ref). Refer to institutional protocols.

Opioid-naive patients: Immediate release: Oral: Usual dosage range: 5 to 10 mg every 4 to 6 hours as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. Dosing is based on severity of pain and patient-specific factors; reduced dosing may be indicated in patients with comorbidities (Ref).

Chronic pain, including chronic cancer pain

Chronic pain, including chronic cancer pain:

Note: Before starting opioid therapy for chronic pain, establish realistic goals for pain and function, and consider how therapy will be discontinued if benefits do not outweigh risks (Ref). Opioids, including oxycodone, are not the preferred therapy for chronic noncancer pain due to insufficient evidence of benefit and risk of serious harm; nonpharmacologic treatment and nonopioid analgesics are preferred, with the exception of chronic pain from active cancer, sickle cell disease, and end-of-life care. Consider opioids, including oxycodone, only in patients who experience clinically meaningful improvement in pain and function that outweighs patient safety risks (Ref).

Opioid-naive patients: In general, for noncancer pain, establish oxycodone requirement using IR formulations (Ref). In patients with cancer pain, may switch to a long-acting formulation earlier in the course of therapy (Ref).

Noncancer or cancer pain: Immediate release:

Oral: Initial: 2.5 to 10 mg every 4 to 6 hours as needed or scheduled around the clock (eg, cancer pain); adjust dose according to patient response (see "Titration" below). Usual maintenance dosage range: 5 to 15 mg every 4 to 6 hours as needed or scheduled around the clock. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. Dosing is based on severity of pain and patient-specific factors; start at the lower end of dosing range (Ref).

Titration:

Noncancer pain: Adjust dose according to patient response; if needed, increase the dose slowly in increments of no more than 25% to 50% of the total daily dose (Ref). Note: To reduce risk of overdose in noncancer pain (excluding patients with sickle cell disease and palliative care), use caution when increasing opioid dosage to ≥50 MME/day (equivalent to ≥33 mg oxycodone/day) and avoid increasing dosage to ≥90 MME/day (equivalent to ≥60 mg oxycodone/day) (Ref).

Cancer pain: Adjust dose according to patient response; if needed, increase the fixed scheduled dose by 30% to 100% of the total dose taken in the prior 24-hour period including total amount of rescue medication used; if pain score decreased and functional assessment improved, continue current effective dosing (Ref).

Rectal [Canadian product]: Usual dosage range: One (10 or 20 mg) suppository up to 3 to 4 times daily as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies (Ref).

Opioid-tolerant patients (also refer to "Dose Conversions for Pain Management"):

Extended release:

Note: Dosage forms: Dose of ER capsules is expressed as oxycodone base and dose of ER tablets is expressed as oxycodone hydrochloride; 9 mg of oxycodone base is equivalent to 10 mg oxycodone hydrochloride. Oxycodone ER capsules and ER tablets are not bioequivalent; monitor for changes in efficacy or tolerability and adjust dose if needed. Place in therapy: Although manufacturer's labeling contains directions for initiating ER oxycodone products in patients who are opioid-naive with chronic pain, these preparations should not be used as initial therapy. Instead, initiate treatment with an IR preparation to more accurately determine the daily opioid requirement and decrease the risk of overdose. Unless pain is associated with cancer, palliative care, or sickle cell disease, the CDC recommends that ER opioids be reserved for patients who have received IR opioids daily for ≥1 week yet continue to experience severe, continuous pain (Ref).

ER tablet (oxycodone hydrochloride): Oral: See "Dose Conversions for Pain Management." Calculated dose may be administered every 12 hours.

ER capsule (oxycodone base): Oral: See "Dose Conversions for Pain Management." Calculated dose may be administered every 12 hours. Maximum dose: 288 mg/day; safety of excipients in higher daily doses has not been established.

Titration: After initiation of oxycodone ER, adjust dose in increments of 25% to 50% no more frequently than every 1 to 2 days until desired pain control. Patients may require rescue doses of an IR analgesic during dose titration. Observe for signs and symptoms of opioid withdrawal or signs of oversedation/toxicity; if unacceptable adverse reactions occur, reduce the dose. To reduce risk of overdose in noncancer pain (excluding patients with sickle cell disease and palliative care), use caution when increasing opioid dosage to ≥50 MME/day (equivalent to ≥33 mg oxycodone/day) and avoid increasing dosage to ≥90 MME/day (equivalent to ≥60 mg oxycodone/day) (Ref). Note: Some clinicians have reported better efficacy with more frequent dosing (ie, every 8 hours) (Ref); however, dosing more frequently than every 12 hours is not recommended by the manufacturer and safety has not been established.

Dose conversions for pain management:

Note: Equianalgesic conversions serve only as a general guide to estimate opioid dose equivalents for patients on scheduled doses of opioids. Multiple factors must be considered for safely individualizing conversion of opioid analgesia. In general, for noncancer pain, the decision to convert from an IR to an ER formulation should be individualized and reserved for those with severe continuous pain who have been taking opioids for ≥1 week (Ref).

Converting from IR oxycodone to ER oxycodone preparations: Total daily oral oxycodone dose may be administered in 2 divided doses. Note: Dose of ER capsules is expressed as oxycodone base and the dose of ER tablets and IR formulations is expressed as oxycodone hydrochloride; 9 mg of oxycodone base is equivalent to 10 mg oxycodone hydrochloride.

Converting between ER oxycodone preparations: Dose of ER capsules is expressed as oxycodone base and the dose of ER tablets is expressed as oxycodone hydrochloride; 9 mg of oxycodone base is equivalent to 10 mg oxycodone hydrochloride. Oxycodone ER capsules and ER tablets are not bioequivalent; monitor for changes in efficacy or tolerability and adjust dose if needed.

Converting to/from oxycodone to/from a different opioid (parenteral or oral): Refer to published equianalgesic opioid conversion data (or institutional protocols) for guidance. Conversion ratios are only approximations and substantial interpatient variability exists; therefore, it is safer to underestimate a patient’s daily oral requirement and provide breakthrough pain relief with IR formulations than to risk overestimating daily requirements. When switching to a new opioid (except to/from methadone), reduce initial daily calculated equianalgesic dose of the new opioid by 25% to 50% to adjust for lack of complete mu receptor cross-tolerance (conversions to/from methadone are highly variable and require extreme caution) (Ref).

Converting from transdermal fentanyl to oxycodone ER: Remove fentanyl patch at least 18 hours prior to starting oxycodone ER. The manufacturer suggests a conservative conversion approach of substituting each fentanyl 25 mcg/hour transdermal patch with 9 mg every 12 hours (oxycodone ER capsule) or 10 mg every 12 hours (oxycodone ER tablets). Systematic assessment of this suggested conversion has not been completed; monitor patients closely.

Converting from methadone to oxycodone ER: Extreme caution and 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.

Discontinuation or tapering of therapy:

When reducing the dose, discontinuing, or tapering long-term opioid therapy, the dose should be gradually tapered. An optimal tapering schedule has not been established (Ref). Proposed schedules range from slow (eg, 10% reduction per week or 10% reduction per month depending on duration of long-term therapy) to rapid (eg, 25% to 50% reduction every few days) (Ref). Individualize dosing based on discussions with patient to minimize withdrawal while considering patient-specific goals and concerns, as well as the opioid’s pharmacokinetics. Slower tapers may be appropriate after long-term use (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse effects (Ref). During tapering, patients may be at an increased risk of overdose if they return to their original (or higher) opioid dose or use illicit opioids, due to rapid loss of tolerance; consider prescribing naloxone (Ref). 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 (Ref). Continue to offer nonopioid analgesics as needed for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms (eg, GI symptoms, muscle spasm) as needed (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: There are no specific dose adjustments provided in the manufacturer's labeling. Oxycodone is excreted as parent drug (~10%) and as active to weakly active metabolites (~47%) with varying degrees of analgesic activity (Ref); half-life is prolonged and accumulation of active metabolites occurs in patients with kidney impairment (Ref). Use of other opioids may be preferred for management of severe pain in patients with kidney impairment (Ref).

Note: When making dose adjustments for the rectal formulation [Canadian product], do not break, crush, cut, or dissolve the suppositories.

Altered kidney function:

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl 30 to <60 mL/minute:

Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% to 75% of usual dose no more frequently than every 6 hours (Ref). Use with caution; titrate gradually based on patient response and adverse effects.

Extended release: Oral: Initial: Administer 50% to 75% of usual dose every 12 to 24 hours; if the reduced dose is less than smallest available dosage form, consider alternative analgesic. Use with caution; titrate gradually based on patient response and adverse effects (Ref).

CrCl <30 mL/minute:

Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 8 hours. Use with caution; titrate gradually based on patient response and adverse effects (Ref).

Extended release: Oral: ER formulations should preferably be avoided in patients with severe impairment (Ref).

Hemodialysis, intermittent (thrice weekly): Slightly dialyzable (10.6%) (Ref):

Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 8 hours; titrate gradually based on patient response and adverse effects (Ref). Use with caution; cases of oxycodone toxicity have been reported in hemodialysis patients (Ref).

Extended release: Oral: ER formulations should preferably be avoided in patients with severe impairment (Ref).

Peritoneal dialysis:

Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 8 hours; titrate gradually based on patient response and adverse effects (Ref); use with caution.

Extended release: Oral: ER formulations should preferably be avoided in patients with severe impairment (Ref).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response (analgesia) and adverse reactions (eg, sedation, CNS and respiratory depression) due to drug accumulation is important.

Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 6 hours; titrate gradually based on patient response and adverse effects (Ref).

Extended release: Oral: Avoid use.

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response (analgesia) and adverse reactions (eg, sedation, CNS and respiratory depression) due to drug accumulation is important.

Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of usual dose no more frequently than every 6 hours; titrate gradually based on patient response and adverse effects (Ref).

Extended release: Oral: Avoid use.

Dosing: Hepatic Impairment: Adult

Immediate release: Initiate therapy at 33% to 50% the usual dosage and titrate carefully. For patients with severe impairment, consider extending the dosing interval based on response and tolerability (eg, every 6 to 12 hours) (Ref).

Extended release tablets or Extended release capsules: 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: Pediatric

(For additional information see "Oxycodone: Pediatric drug information")

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

Analgesia, moderate to severe pain: Limited data available:

Infants ≤6 months: Immediate release: Oral solution (1 mg/mL): Oral: Initial dose: 0.025 to 0.05 mg/kg/dose every 4 to 6 hours as needed (Ref).

Infants >6 months, Children, and Adolescents:

Patient weight <50 kg: Immediate release: Oral: 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/dose (Ref).

Patient weight ≥50 kg: Immediate release: Oral: 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 (Ref).

Analgesia, severe pain requiring around-the-clock long-term opioid therapy

Analgesia, severe pain requiring around-the-clock long-term opioid therapy: Note: Use only in pediatric patients ≥11 years of age who are already receiving opioid therapy for ≥5 consecutive days, tolerating a minimum daily opioid dose of ≥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.

Children ≥11 years and Adolescents: Extended-release tablets (eg, OxyContin): 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 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).

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

Conversion factor

Oral

Parenterala

Oxycodone

1

--

Hydrocodone

0.9

--

Hydromorphone

4

20

Morphine

0.5

3

Tramadol

0.17

0.2

a 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 ≥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.

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 (Ref). Specific pediatric protocols are lacking; based on experience in adults, proposed schedules range from slow (eg, 10% reductions per week) to rapid (eg, 25% to 50% reduction every few days) (Ref). 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 (Ref). 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, or pausing the taper and restarting when the patient is ready (Ref). Continue to offer nonopioid analgesics as needed for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

In general, oxycodone clearance may be decreased in patients with renal impairment; initiate therapy at low end of dosing range.

Immediate release: Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following adjustments have been recommended (Ref):

GFR ≥50 mL/minute/1.73 m2: No dosage adjustment required.

GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of dose.

GFR <10 mL/minute/1.73 m2: Administer 50% of dose.

Hemodialysis: Administer 50% of dose posthemodialysis.

Peritoneal dialysis: Administer 50% of dose.

Extended-release tablets (eg, OxyContin): Children ≥11 years and Adolescents: CrCl <60 mL/minute: Serum concentrations are increased ~50%. Initiate at the low end of the dosage range (use caution); adjust dose as clinically indicated. Doses of 33% to 50% of usual initial dosing have been recommended; if the reduced dose is less than smallest available dosage form, consider alternative analgesic.

Dosing: Hepatic Impairment: Pediatric

Immediate release: There are no dosage adjustments provided in the manufacturer's labeling; based on experience in adult patients, may consider a conservative approach of reduced initial doses; adjust dose based on clinical response.

Extended-release tablets (eg, OxyContin): Children ≥11 years and Adolescents: Initial: One-third (1/3) to one-half (1/2) of the usual starting dose; carefully titrate dose to appropriate effect. If reduced dose is less than smallest available dosage form, consider alternative analgesic.

Dosing: Older Adult

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

Dosage Forms: US

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 (30 mL)

Solution, Oral, as hydrochloride:

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

Tablet, Oral, as hydrochloride:

Oxaydo: 5 mg, 7.5 mg

Roxicodone: 5 mg [DSC] [scored]

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

Roxicodone: 30 mg [scored]

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

Tablet Abuse-Deterrent, Oral:

RoxyBond: 15 mg, 30 mg [contains fd&c blue #2 (indigotine)]

Tablet Abuse-Deterrent, Oral, as hydrochloride:

RoxyBond: 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 (indigo carm) aluminum lake]

Generic: 10 mg, 15 mg [DSC], 20 mg, 30 mg [DSC], 40 mg, 60 mg [DSC], 80 mg

Generic Equivalent Available: US

May be product dependent

Dosage Forms Considerations

Xtampza ER: Strength is expressed in terms of oxycodone base.

9 mg equivalent to 10 mg oxycodone hydrochloride

13.5 mg equivalent to 15 mg oxycodone hydrochloride

18 mg equivalent to 20 mg oxycodone hydrochloride

27 mg equivalent to 30 mg oxycodone hydrochloride

36 mg equivalent to 40 mg oxycodone hydrochloride

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Suppository, Rectal:

Supeudol 10: 10 mg (12 ea)

Supeudol 20: 20 mg (12 ea)

Tablet, Oral, as hydrochloride:

Oxy-IR: 5 mg, 10 mg, 20 mg

Supeudol: 5 mg, 10 mg, 20 mg

Generic: 5 mg, 10 mg, 20 mg

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

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

OxyNEO: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Tablet Extended Release 12 Hour, Oral:

Generic: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg

Controlled Substance

C-II

Administration: Adult

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

ER dosage forms:

Oral:

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.

Bariatric surgery: Tablet, abuse deterrent and extended or controlled release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Roxybond (oxycodone) tablets are formulated to have increased resistance to cutting, crushing, grinding, or breaking. Pharmacokinetics are similar to other IR oxycodone formulations. Nonabuse-deterrent IR tablet, capsule, and oral solution formulations are available. Oxycodone ER capsule contents may be taken by sprinkling the contents onto soft food (ie, applesauce, ice cream, yogurt). If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, clinicians should be advised that oral morphine has been shown to have significantly increased Cmax and decreased Tmax in the immediate (1 to 2 weeks) and long-term (6-months) period after bariatric surgery.

IR dosage forms:

Oral:

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) may be used in opioid-tolerant patients (taking ≥30 mg/day of oxycodone or equivalent for ≥1 week); may also be used in palliative care patients who have difficulty and/or are unable to swallow. The concentrate is not substantially absorbed sublingually/orally and requires the GI tract for effective absorption (Ref).

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.

Rectal:

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

Administration: Pediatric

Oral:

Immediate release (capsule, oral solution, tablets): May administer with food to decrease GI upset:

Oral solution: Available in 2 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).

Tablet (Oxaydo): Swallow whole with adequate water to ensure complete swallowing immediately after placing in the mouth; the formulation uses technology designed to discourage common methods of tampering to prevent misuse/abuse. The tablet should not be wet prior to placing in the mouth. Do not crush, chew, or dissolve nor administer via feeding tubes (eg, gastric, NG) due to potential for obstruction.

Extended release: Tablet (eg, OxyContin): May administer with food to decrease GI upset. Swallow whole; do not moisten, dissolve, cut, crush, chew, or break as this would result in rapid release of oxycodone and absorption of a potentially fatal dose of drug. Administer one at a time and follow each with water immediately after placing in the mouth. For oral use only; do not administer rectally; increased risk of adverse events due to better rectal absorption.

Use: Labeled Indications

Pain management:

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

Extended release:

Capsules (Xtampza ER): 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 (Oxycontin): 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.

Medication Safety Issues
Sound-alike/look-alike issues:

OxyCODONE may be confused with HYDROcodone, oxybutynin, OxyCONTIN, oxyMORphone

OxyCONTIN may be confused with MS Contin, oxybutynin, oxyMORphone

OxyFast may be confused with Roxanol

Roxicodone may be confused with Roxanol

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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

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.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, 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. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately (eg, calling 911) in the event of known or suspected overdose.

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 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. Consider prescribing naloxone for emergency treatment of opioid overdose in patients taking benzodiazepines or other CNS depressants concomitantly with opioids.

• 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.

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.

• Older adult: Use with caution in elderly patients; 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 suggest 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 [MME]/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-based opioid use disorder treatment) 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 antiseizure medications 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 IR opioids (instead of ER/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 MME/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]).

• Naloxone access: Discuss the availability of naloxone with all patients who are prescribed opioid analgesics, as well as their caregivers, and consider prescribing it to patients who are at increased risk of opioid overdose. These include patients who are also taking benzodiazepines or other CNS depressants, have an opioid use disorder (OUD) (current or history of), or have experienced a previous opioid overdose. Additionally, health care providers should consider prescribing naloxone to patients prescribed medications to treat OUD; patients at risk of opioid overdose even if they are not taking an opioid analgesic or medication to treat OUD; and patients taking opioids, including methadone or buprenorphine for OUD, if they have household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose. Inform patients and caregivers on options for obtaining naloxone (eg, by prescription, directly from a pharmacist, a community-based program) as permitted by state dispensing and prescribing guidelines. Educate patients and caregivers on how to recognize respiratory depression, proper administration of naloxone, and getting emergency help.

• 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.

Metabolism/Transport Effects

Substrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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. Risk D: Consider therapy modification

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

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

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

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

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

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: 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. Risk D: Consider therapy modification

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

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: 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. Risk D: Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: 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. Risk C: Monitor therapy

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

Desmopressin: Opioid Agonists may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: 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. Risk D: Consider therapy modification

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

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

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

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

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

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

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. Risk D: Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: 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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

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

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

Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: 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. Risk X: Avoid combination

Nefazodone: Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4). Management: If concomitant use of opioid agonists that are metabolized by CYP3A4 and nefazodone is necessary, consider dose reduction of the opioid until stable drug effects are achieved. Monitor for increased opioid effects and serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

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. Risk X: Avoid combination

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

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

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

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

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. Risk D: Consider therapy modification

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

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: 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. Risk D: Consider therapy modification

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

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

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

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

Samidorphan: May diminish the therapeutic effect of Opioid Agonists. Risk X: Avoid combination

Serotonergic Agents (High Risk): Opioid Agonists (metabolized by CYP3A4) 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. Risk C: 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. Risk D: Consider therapy modification

Somatostatin Analogs: Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs. Risk C: Monitor therapy

Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Risk C: 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. Risk D: Consider therapy modification

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

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

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. Risk D: Consider therapy modification

Reproductive Considerations

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

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).

Breastfeeding Considerations

Oxycodone is present in breast milk in variable concentrations.

In one study, oxycodone was measurable in breast milk up to 37 hours after the last maternal dose and therapeutic concentrations were detected in the serum of a breastfeeding infant (Seaton 2007). Oxycodone was also detected in the urine of a breastfed infant (Sulton-Villavasso 2012).

CNS depression, constipation, decreased feeding, and respiratory distress/irregular breathing have been observed in infants exposed to oxycodone via breast milk (Lam 2012; Sulton-Villavasso 2012). Withdrawal symptoms may occur when maternal use is discontinued or breastfeeding is stopped.

Nonopioid analgesics are preferred for breastfeeding females who require pain control peripartum or for surgery outside of the postpartum period (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]). When an opiate is needed, use of oxycodone in breastfeeding women is not recommended by some guidelines (Sachs 2013). Other guidelines note prolonged and frequent use may cause neonatal sedation (ABM [Martin 2018]). Maternal doses greater than 30 mg/day are not recommended (ABM [Martin 2018]; ACOG 209 2019).

When opioids are needed in breastfeeding women, the lowest effective dose for the shortest duration of time should be used to limit adverse events in the mother and breastfeeding infant. In general, a single occasional dose of an opioid analgesic may be compatible with breastfeeding (WHO 2002). Breastfeeding women using opioids for postpartum pain or for the treatment of chronic maternal pain should monitor their infants for drowsiness, sedation, feeding difficulties, or limpness (ACOG 209 2019).

Dietary Considerations

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

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-based opioid use disorder treatment): 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]).

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

Onset of action: Pain relief: Immediate release: 10 to 15 minutes.

Peak effect: Immediate release: 0.5 to 1 hour.

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

Distribution: Vd: 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.

Protein binding: 38% to 45%.

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

Bioavailability: Extended release tablet, immediate release: 60% to 87%; Extended release capsule is not bioequivalent to extended release tablet; however AUC, is similar in a fed state.

Half-life:

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%.

Time to peak, plasma: Immediate release: 1.2 to 1.9 hours; Extended release: 4 to 5 hours.

Excretion: Urine: (~10% as parent; ~65% as metabolites [noroxycodone (23%, active), oxymorphone (10%, active), noroxymorphone (14%, weakly active), reduced metabolites (≤18%)]) (Kinnunen 2019).

Pharmacokinetics: Additional Considerations

Altered kidney function: 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.

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.

Pricing: US

Capsule ER 12 Hour Abuse-Deterrent (Xtampza ER Oral)

9 mg (per each): $7.10

13.5 mg (per each): $10.45

18 mg (per each): $13.25

27 mg (per each): $18.43

36 mg (per each): $22.69

Capsules (oxyCODONE HCl Oral)

5 mg (per each): $1.84 - $1.85

Concentrate (oxyCODONE HCl Oral)

100 mg/5 mL (per mL): $4.17 - $12.33

Solution (oxyCODONE HCl Oral)

5 mg/5 mL (per mL): $1.05 - $1.73

Tablet Abuse-Deterrent (RoxyBond Oral)

5 mg (per each): $13.12

15 mg (per each): $15.88

30 mg (per each): $21.40

Tablet ER 12 Hour Abuse-Deterrent (oxyCODONE HCl ER Oral)

10 mg (per each): $3.02 - $5.03

20 mg (per each): $5.64 - $9.37

40 mg (per each): $8.36 - $16.05

80 mg (per each): $15.73 - $28.01

Tablet ER 12 Hour Abuse-Deterrent (OxyCONTIN Oral)

10 mg (per each): $5.74

15 mg (per each): $8.44

20 mg (per each): $10.69

30 mg (per each): $14.88

40 mg (per each): $18.31

60 mg (per each): $25.93

80 mg (per each): $31.96

Tablets (Oxaydo Oral)

5 mg (per each): $11.70

7.5 mg (per each): $17.53

Tablets (oxyCODONE HCl Oral)

5 mg (per each): $0.08 - $0.62

10 mg (per each): $0.15 - $1.45

15 mg (per each): $0.12 - $2.37

20 mg (per each): $0.27 - $2.32

30 mg (per each): $0.18 - $4.49

Tablets (Roxicodone Oral)

15 mg (per each): $6.23

30 mg (per each): $12.23

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Abtard (GB);
  • Alnagon (RO);
  • Dancex (IE);
  • Endone (AU);
  • Epethinan (IE);
  • Ircodon (KR);
  • Lynlor (GB);
  • M-Oxy (PE);
  • Orionox (FI, NO);
  • Oxinovag (AR);
  • Oxycod (IL);
  • OxyContin (AR, AT, BR, CH, CL, CO, CR, CY, CZ, DK, DO, EC, EE, ES, FI, GB, GT, HK, HN, IE, IL, IT, MY, NI, NL, NO, NZ, PA, PE, PH, PL, PT, SE, SG, SV, VE);
  • Oxycontin (BB, BH, CN, HR, HU, IS, LB, LU, RO, SI, SK, TR, TW, VN, ZA);
  • Oxycontin CR (KR);
  • Oxycontin LP (FR);
  • Oxycontin Neo (PH);
  • Oxyduo (PL);
  • Oxyfast (JP);
  • Oxygesic (DE);
  • Oxyneo (ID, VN);
  • Oxynorm (AT, AU, BE, CH, CY, DK, EG, ES, FI, FR, GB, HK, ID, IE, IS, MY, NO, NZ, PH, SE, SG, TR, TW, ZA);
  • OxyNorm (JP);
  • Oxynorm IV (SG);
  • Plexicodim (MX);
  • Proladone (AU);
  • Reltebon (GB, HU);
  • Targin (DE, IL)


For country code abbreviations (show table)
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  44. Oxycodone hydrochloride capsules [prescribing information]. Allentown, PA: Genus Lifesciences Inc; July 2021.
  45. Oxycodone hydrochloride 1 mg/mL oral solution [prescribing information]. Allentown, PA: Genus Lifesciences Inc; July 2021.
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