Version July 2025
Because the use of 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 and reassess all patients regularly for the development of these behaviors and conditions.
Health care providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription.
Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of oxycodone are essential. 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 of even one dose of oxycodone, especially by children, can result in a fatal overdose of oxycodone.
If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome (NOWS), which may be life threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery.
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. Regularly evaluate patients receiving oxycodone and any CYP3A4 inhibitor or inducer.
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.
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 and death.
Dosage guidance:
Safety: Consider prescribing naloxone or nalmefene for patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, patients with sleep-disordered breathing, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally), and/or concomitant benzodiazepine use (Ref).
Dosing: Dosing provided is based on typical doses; some patients may require higher or lower doses. Individualize dosing based on patient-specific factors (eg, comorbidities, severity of pain, 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.
Clinical considerations: Opioids may be part of a comprehensive, multimodal, patient-specific treatment plan for managing moderate to severe pain. Maximize nonopioid analgesia, if appropriate, prior to initiation of opioid analgesia (Ref).
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 pain severe enough to require opioids. Long-acting preparations for treatment of acute pain in opioid-naive patients should generally be avoided (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 opioid-tolerant patients (eg, breakthrough cancer pain):
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, post anesthesia 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 (Ref). Some experts use 5 to 10 mg every 3 to 4 hours as needed (Ref).
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. 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: 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: Dosages ≥50 morphine milligram equivalents (MME)/day are likely to not have increased benefits in pain relief or function relative to overall risks. To reduce risk of overdose in noncancer pain (excluding patients with sickle cell disease and palliative care), readdress pain and reassess evidence of individual benefits and risks when increasing opioid dosage to ≥50 MME/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, reserve ER opioids 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. Dosages ≥50 MME/day are likely to not have increased benefits in pain relief or function relative to overall risks. To reduce risk of overdose in noncancer pain (excluding patients with sickle cell disease and palliative care), readdress pain and reassess evidence of individual benefits and risks when increasing opioid dosage to ≥50 MME/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. Individualize tapering based on discussions with patient to minimize withdrawal, while considering patient-specific goals and concerns and the opioid's pharmacokinetics. Proposed initial 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). Slower tapers may be appropriate after long-term use (eg, >1 year), whereas more rapid tapers may be appropriate in patients experiencing severe adverse effects. 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 or nalmefene. 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 autonomic withdrawal symptoms and other adjunctive agents to treat GI symptoms and muscle spasms, as needed. Continue to offer nonopioid analgesics as needed for pain management during the taper (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: In patients with liver impairment, monitor closely for respiratory and CNS depression and worsening hepatic encephalopathy or opioid-induced neurotoxicity (eg, myoclonus, hyperalgesia, delirium, confusion, disorientation) following initiation of therapy and during titration (Ref). Ensure appropriate prophylaxis against hepatic encephalopathy and constipation (eg, lactulose) are employed (Ref).
When making dose adjustments for the rectal formulation [Canadian product], do not break, crush, cut, or dissolve the suppositories.
Hepatic impairment leads to an increase in oxycodone bioavailability (increased by 50% to 95%), prolonged action of pharmacologically active metabolites, and the risk of accumulation and related adverse effects (Ref).
Liver impairment prior to treatment initiation:
Initial or dose adjustment in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A through C:
Immediate release: Oral, rectal [Canadian product]: Initial: Administer 50% of the usual indication-specific dose and administer no more frequently than every 6 hours; further extending the dosing interval should be considered to avoid or minimize drug accumulation following administration of multiple doses. If necessary, may increase dose based on response and tolerability (Ref).
Extended release: Oral: Avoid use (Ref).
Note: Minimize opioid use in older adults unless for the management of severe acute pain. Opioids are associated with an increased risk of falls and inducing or worsening delirium in older adults (Ref).
Refer to adult dosing. Initiate therapy at low end of dosing range and use caution.
(For additional information see "Oxycodone: Pediatric drug information")
Dosage guidance:
Safety: 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:
Pain, moderate to severe: 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).
Pain, severe, 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).
|
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.
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.
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.
Opioid-induced constipation (OIC) is the most common subtype of opioid-induced bowel dysfunction, which is a broader term that encompasses additional GI opioid-induced adverse reactions including nausea, vomiting, and gastroesophageal reflux. Symptoms of OIC may include decreased frequency of bowel movements, straining to pass bowel movements, a sense of incomplete evacuation, and/or hard stools (Ref). Tolerance does not develop to OIC (Müller-Lissner 2017, Rossi 2019). Symptoms are reversible after discontinuation of the opioid (Ref). OIC is the most common reason for discontinuation reported by patients and may often result in a longer hospital stay and increased overall healthcare costs (Ref). Opioid dose or route of administration does not appear to alter risk (Ref).
Mechanism: Time-related; mu-opioid receptor stimulation in the GI tract results in delayed gastric emptying, decreased peristalsis, decreased water and chloride secretion into the intestinal lumen, and slowed bowel motility (Ref).
Onset: Varied; changes in peristalsis may occur 5 to 25 minutes after administration of opioids (Ref). However, OIC is defined based on a 7-day period of change (Ref).
Risk factors:
• Increased dosing frequency (ie, daily vs 2 to 3 times per week) (Ref)
• Chronic opioid administration (Ref)
• Concurrent use of other medications that cause constipation
Opioid-induced neurotoxicity is an opioid-related adverse drug reaction more commonly associated with opioids that have active metabolites (eg, codeine, hydromorphone, meperidine, morphine, oxycodone). Symptoms may include allodynia, delirium, hallucinations, hyperalgesia, hypersomnolence, myoclonus, tremor, and seizures (Ref).
Mechanism: Not clearly established; hypothesized to result from an accumulation of neuroexcitatory opioid metabolites (Ref).
Risk factors:
• High opioid dose (Ref)
• Dehydration (Ref)
• Kidney failure (Ref)
• Infection (Ref)
• Advanced age (Ref)
Serious, life-threatening, or fatal opioid-induced respiratory depression (OIRD) may occur with use of oxycodone in adult and pediatric patients. Effects include hypoventilation, hypoxia, hypercapnia, and respiratory acidosis, as well as reduced ventilatory responses to hypoxia and hypercapnia (Ref).
Mechanism: Dose-related; stimulation of mu-opioid receptors in the brainstem leads to suppression of the respiratory control network and depression of normal hypoxic and hypercapnic ventilatory responses (Ref).
Onset: Rapid; OIRD reported within 2 hours after administration of oxycodone IR capsule (Ref).
Risk factors:
• Higher doses of intraoperative opioids (eg, morphine-equivalent daily dose ~40 mg in opioid-naïve patients) (Ref)
• Initiation of therapy or dose increase
• Opioid naïve (Ref)
• Opioid misuse (Ref)
• Acute overdose
• Concurrent administration of benzodiazepines, alcohol, or other CNS depressants
• Postoperative patients with comorbid cardiac or respiratory disease (Ref)
• Age >60 years (Ref)
• Males (Ref)
• Sleep disorder (eg, obstructive sleep apnea) (Ref)
• Chronic pulmonary disease
• Cachexia
• Debilitation
Abruptly stopping or reducing opioid use in patients with physical dependence on opioids can precipitate opioid-induced withdrawal (OIW) in adult and pediatric patients (Ref). Physical symptoms may include nausea, vomiting, diarrhea, abdominal cramps, tachycardia, chills, muscle aches, bone pain, agitation, anxiety, and insomnia. Psychosis has also been reported in case reports and case series (Ref). The presence and severity of withdrawal symptoms are associated with an increased risk of nonfatal overdose and receptive syringe sharing in people who inject drugs (Ref). Avoidance of withdrawal symptoms may drive continued opioid use (Kosten 2019). Symptoms typically dissipate over 4 to 7 days (Ref).
Mechanism: Withdrawal; opioids bind to mu-opioid receptors on neurons in the locus coeruleus (LC) of the brainstem, causing decreased norepinephrine (NE) release. Upon abrupt discontinuation, the absence of opioid stimulation causes LC hyperactivity, excessive NE release, and subsequent autonomic hyperactivity (Ref).
Onset: Rapid; symptoms typically occur within 12 hours of discontinuation and peak at 36 to 72 hours; varies based on half-life of opioid (Ref).
Risk factors:
• Higher cumulative dose (Ref)
• Prolonged exposure to opioids (Ref)
• Initiation of mixed agonist/antagonist or partial agonist analgesics (eg, buprenorphine, butorphanol, nalbuphine, pentazocine) (Ref) in patients currently or recently taking full mu-opioid agonists may cause precipitated opioid withdrawal. (Precipitated withdrawal is similar to OIW, but with a faster onset (Ref).
• Opioid use disorder (Ref)
• Abrupt discontinuation or dose reduction (Ref)
• Concurrent use of benzodiazepines (Ref) or antipsychotics (Ref)
• Age <6 years, especially infants <6 months of age (Ref)
• Preexisting cognitive impairment (Ref)
• Critical illness involving CNS (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions for the immediate release (IR) product reported in adults and in adolescents and adults for the extended release (ER) product unless otherwise indicated.
>10%:
Dermatologic: Pruritus (ER: 3% to 13%; IR: ≥3%)
Gastrointestinal: Constipation (ER: 5% to 23%; IR: ≥3%) (table 1), nausea (ER: 11% to 23%; IR: ≥3%), vomiting (ER: 4% to 21%; IR: ≥3%)
|
Drug (Oxycodone) |
Placebo |
Population |
Dosage Form |
Indication |
Number of Patients (Oxycodone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
9% |
N/A |
Adolescents |
Extended-release tablets |
N/A |
140 |
N/A |
|
5% |
0.5% |
N/A |
Extended-release capsules |
Moderate to severe chronic lower back pain |
193 |
196 |
|
23% |
7% |
N/A |
Extended-release tablets |
N/A |
227 |
45 |
|
≥3% |
N/A |
N/A |
Immediate-release tablets |
N/A |
191 |
N/A |
Nervous system: Dizziness (ER: 2% to 13%; IR: ≥3%), drowsiness (ER [adults]: 9% to 23%; ER [adolescents]: 1% to 5%; IR: ≥3%), headache (ER: 14%; IR: ≥3%)
Miscellaneous: Fever (ER: 1% to 11%; IR: ≥3%)
1% to 10%:
Cardiovascular: Deep vein thrombosis (IR: <3%), edema (≤5%), flushing (ER [adults]: 1% to 5%), heart failure (IR: <3%), hypertension (ER [adults]: 1% to 5%), hypotension (IR: <3%), orthostatic hypotension (ER: 1% to 5%), palpitations (IR: <3%), peripheral edema (<3%), tachycardia (≤5%), thrombophlebitis (IR: <3%), vasodilation (IR: <3%)
Dermatologic: Diaphoresis (≤5%), excoriation of skin (ER [adults]: 1% to 5%), hyperhidrosis (≤5%), skin photosensitivity (IR: <3%), skin rash (≤5%), urticaria (IR: <3%)
Endocrine & metabolic: Hyperglycemia (≤5%), hypochloremia (ER [adolescents]: 1% to 5%), hyponatremia (ER [adolescents]: 1% to 5%), weight loss (ER [adolescents]: 1% to 5%)
Gastrointestinal: Abdominal pain (≤5%, including upper abdominal pain), anorexia (≤5%), decreased appetite (≤5%), diarrhea (≤6%), dyspepsia (≤5%), dysphagia (<3%), gastritis (ER: 1% to 5%), gastroesophageal reflux disease (ER: 1% to 5%), gingivitis (IR: <3%), glossitis (IR: <3%), hiccups (ER: 1% to 5%), xerostomia (≤6%)
Genitourinary: Dysuria (ER [adolescents]: 1% to 5%; ER [adults]: <1%), urinary retention (ER [adolescents]: 1% to 5%; ER [adults]: <1%), urinary tract infection (IR: <3%)
Hematologic & oncologic: Anemia (IR: <3%, including iron deficiency anemia), decreased platelet count (ER [adolescents]: 1% to 5%), decreased red blood cells (ER [adolescents]: 1% to 5%), febrile neutropenia (ER [adolescents]: 1% to 5%), hemorrhage (IR: <3%), leukopenia (IR: <3%), neutropenia (ER [adolescents]: 1% to 5%)
Hepatic: Increased serum alanine aminotransferase (ER [adolescents]: 1% to 5%)
Hypersensitivity: Hypersensitivity reaction (IR: <3%)
Infection: Herpes simplex infection (IR: <3%), infection (IR: <3%), sepsis (IR: <3%)
Nervous system: Abnormal dreams (ER: ≤5%), agitation (≤5%), anxiety (≤5%), asthenia (1% to 6%), changes in thinking (ER: 1% to 5%), chills (≤5%), confusion (≤5%), depression (ER [adolescents]: 1% to 5%; ER [adults]: <1%), dysphoria (ER: 1% to 5%), euphoria (ER: ≤5%), fatigue (ER: 1% to 5%), hypertonia (IR: <3%), hypoesthesia (≤5%), insomnia (ER: 1% to 5%; IR: ≥3%), irritability (ER [adults]: 1% to 5%), lethargy (ER: 1% to 5%), migraine (adults: ≤5%), nervousness (≤5%), neuralgia (IR: <3%), paresthesia (ER [adolescents]: 1% to 5%; ER [adults]: <1%), personality disorder (IR: <3%), tremor (adults: ≤5%), twitching (ER: 1% to 5%), withdrawal syndrome (ER [adults]: ≤5%)
Neuromuscular & skeletal: Arthralgia (adults: ≤5%), arthritis (IR: <3%), back pain (adults: ≤5%), gout (IR: <3%), laryngospasm (IR: <3%), limb pain (ER [adolescents]: 1% to 5%), musculoskeletal pain (ER: ≤5%), myalgia (≤5%), neck pain (IR: <3%), ostealgia (IR: <3%), pathological fracture (IR: <3%)
Ophthalmic: Amblyopia (IR: <3%), blurred vision (ER [adults]: 1% to 5%)
Respiratory: Bronchitis (IR: <3%), cough (adults: ≤5%), dyspnea (≤5%), epistaxis (IR: <3%), flu-like symptoms (IR: <3%), laryngismus (IR: <3%), oropharyngeal pain (ER: 1% to 5%), oxygen saturation decreased (ER [adolescents]: 1% to 5%), pharyngitis (IR: <3%), rhinitis (IR: <3%), sinusitis (IR: <3%)
Miscellaneous: Accidental injury (<3%), seroma (ER [adolescents]: 1% to 5%)
<1% (any formulation or population):
Cardiovascular: Chest pain, depression of ST segment on ECG, syncope
Dermatologic: Exfoliative dermatitis, night sweats, xeroderma
Endocrine & metabolic: Dehydration, increased thirst
Gastrointestinal: Dysgeusia, eructation, flatulence, increased appetite, stomatitis
Genitourinary: Erectile dysfunction, hematuria, polyuria
Hematologic & oncologic: Lymphadenopathy
Hepatic: Increased gamma-glutamyl transferase
Hypersensitivity: Facial edema
Nervous system: Abnormal gait, amnesia, depersonalization, emotional lability, hallucination, hypotonia, malaise, memory impairment, restlessness, sleep disturbance, speech disturbance, stupor, vertigo, voice disorder
Neuromuscular & skeletal: Hyperkinetic muscle activity
Ophthalmic: Visual disturbance
Otic: Tinnitus
Frequency not defined (any formulation or population):
Cardiovascular: Circulatory depression, shock
Respiratory: Respiratory depression
Postmarketing (any formulation or population):
Endocrine & metabolic: Amenorrhea, SIADH
Gastrointestinal: Cholestasis, dental caries, diverticulitis of the gastrointestinal tract (exacerbation), intestinal obstruction
Genitourinary: Hypogonadism
Hepatic: Increased liver enzymes
Nervous system: Aggressive behavior, allodynia (opioid-induced hyperalgesia) (FDA Safety Communication 2023), drug abuse, hyperalgesia, mood changes, neonatal withdrawal, opioid dependence, seizure, suicidal ideation, suicidal tendencies
Respiratory: Pharyngeal edema
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).
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.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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).
• Hyperalgesia: Opioid-induced hyperalgesia (OIH) has occurred with short-term and prolonged use of opioid analgesics. Symptoms may include increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily nonpainful stimuli; symptoms may be suggestive of OIH if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Consider decreasing the current opioid dose or opioid rotation in patients who experience OIH.
• 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: 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; dosage adjustment may be required.
• 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 potential increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (CDC [Dowell 2022]).
• 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: Use with caution in patients with sleep-related disorders, including sleep apnea, due to increased risk for respiratory and CNS depression. Monitor carefully and titrate dosage cautiously in patients with mild sleep-disordered breathing. Avoid opioids in patients with moderate to severe sleep-disordered breathing (CDC [Dowell 2022]).
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Special populations:
• Older adult: Use opioids with caution in older adults; may be more sensitive to adverse effects. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increased adverse effects. Monitor closely for adverse effects associated with opioid therapy (eg, respiratory and CNS depression, falls, cognitive impairment, constipation) (CDC [Dowell 2022]). Consider the use of alternative nonopioid analgesics in these patients when possible.
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.
Other warnings/precautions:
• Abuse/misuse/diversion: Use with caution in patients with a history of substance abuse disorder; potential for drug dependency exists. Other factors associated with increased risk for misuse include concomitant depression or other mental health conditions, higher opioid dosages, or taking other CNS depressants. Consider offering naloxone or nalmefene prescriptions in patients 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), concomitant benzodiazepine use, and patients at risk for returning to a high dose after losing tolerance (CDC [Dowell 2022]).
• Appropriate use: Outpatient setting: Opioids should not be used as first-line therapy for acute (<1-month duration), subacute (1- to 3-month duration), or chronic pain (>3-month duration [outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-based opioid use disorder treatment]). Preferred management includes nonpharmacologic therapy and non-opioid therapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, certain antiseizure medications and antidepressants) as appropriate for the specific condition. If opioid therapy is initiated, it should be combined with nonpharmacologic and non-opioid therapy, as appropriate. Prior to initiation, known risks and realistic benefits of opioid therapy should be discussed with the patient. Therapy should be initiated at the lowest effective dosage using IR opioids (instead of ER/long-acting opioids). For the treatment of acute pain, therapy should only be given for the expected duration of pain severe enough to require opioids and prescribed as needed (not scheduled). For the treatment of subacute and chronic pain, 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. Risk to patients increases with higher opioid dosages. Dosages ≥50 MME/day are likely to not have increased benefit to pain relief or function relative to overall risk to patients; before increasing dosage to ≥50 MME/day, readdress pain and reassess evidence of individual benefits and risks (CDC [Dowell 2022]).
• Naloxone/Nalmefene access: Discuss the availability of naloxone or nalmefene 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 opioid-induced respiratory depression/opioid overdose. Additionally, health care providers should consider prescribing naloxone or nalmefene 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 or nalmefene (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 or nalmefene, 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: Additional information is available at http://www.opioidanalgesicrems.com or at 1-800-503-0784.
• Surgery: Opioids decrease bowel motility; monitor for decreased bowel motility in postoperative patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.
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
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, 100 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,indigo carmine), 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, as hydrochloride:
RoxyBond: 5 mg
RoxyBond: 10 mg [contains fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10)]
RoxyBond: 15 mg, 30 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 5 mg, 10 mg, 15 mg, 30 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 [DSC], 15 mg [DSC], 20 mg [DSC], 30 mg [DSC], 40 mg [DSC], 60 mg [DSC], 80 mg [DSC]
May be product dependent
Capsule ER 12 Hour Abuse-Deterrent (Xtampza ER Oral)
9 mg (per each): $7.95
13.5 mg (per each): $11.71
18 mg (per each): $14.85
27 mg (per each): $20.65
36 mg (per each): $25.42
Capsules (oxyCODONE HCl Oral)
5 mg (per each): $1.84
Concentrate (oxyCODONE HCl Oral)
100 mg/5 mL (per mL): $5.60 - $12.33
Solution (oxyCODONE HCl Oral)
5 mg/5 mL (per mL): $1.05 - $1.60
Tablet Abuse-Deterrent (oxyCODONE HCl Oral)
5 mg (per each): $16.80
10 mg (per each): $19.79
15 mg (per each): $20.72
30 mg (per each): $27.92
Tablet Abuse-Deterrent (RoxyBond Oral)
5 mg (per each): $18.47
10 mg (per each): $21.76
15 mg (per each): $22.78
30 mg (per each): $30.70
Tablet ER 12 Hour Abuse-Deterrent (OxyCONTIN Oral)
10 mg (per each): $6.98
15 mg (per each): $10.27
20 mg (per each): $13.00
30 mg (per each): $18.09
40 mg (per each): $22.26
60 mg (per each): $31.54
80 mg (per each): $38.86
Tablets (oxyCODONE HCl Oral)
5 mg (per each): $0.16 - $0.62
10 mg (per each): $0.28 - $1.59
15 mg (per each): $0.12 - $2.58
20 mg (per each): $0.51 - $2.32
30 mg (per each): $0.18 - $4.89
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Suppository, Rectal:
Supeudol 10: 10 mg ([DSC])
Supeudol 20: 20 mg ([DSC])
Tablet, Oral, as hydrochloride:
Oxy-IR: 5 mg, 10 mg, 20 mg
Supeudol: 5 mg, 10 mg
Supeudol 20: 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
C-II
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.
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.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Oxaydo: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/202080s013lbl.pdf
Oxycodone hydrochloride capsules: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/200534s013lbl.pdf
Oxycodone hydrochloride oral solution: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/201194s017lbl.pdf
OxyContin: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022272s048lbl.pdf#page=49
Roxybond: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/209777s008lbl.pdf
Roxicodone: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021011s013lbl.pdf
Xtampza ER: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208090s015lbl.pdf#page=39
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 severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate in adults.
Tablets (Oxycontin): Management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic 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: Because of the risks of substance use disorder, abuse, and misuse with opioids, which may occur at any dosage or duration, reserve oxycodone for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) have not been tolerated, or are not expected to be tolerated; have not provided adequate analgesia, or are not expected to provide adequate analgesia. IR formulations are not intended to be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. ER formulations are not indicated as as-needed analgesics.
OxyCODONE may be confused with HYDROcodone, oxyBUTYnin, OxyCONTIN, oxyMORphone
OxyCONTIN may be confused with MS Contin, oxyBUTYnin, oxyCODONE, oxyMORphone, oxytocin
OxyFast may be confused with Roxanol
Roxicodone may be confused with Roxanol
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (opioids, all formulations and routes of administration) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Oxycodone is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) due to an increased risk of exacerbation of constipation. Opioids are not recommended as first-line treatment of mild pain or long-term treatment of osteoarthritis. Short-acting opioids should be available for breakthrough pain in patients on long-acting opioids. Avoid use in patients with a history of recurrent falls (O'Mahony 2023).
Substrate of CYP2D6 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Clinically Relevant Anticholinergic Effects: May increase adverse/toxic effects of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alvimopan: Opioid Agonists may increase adverse/toxic effects 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
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amphetamines: May increase analgesic effects of Opioid Agonists. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
Buprenorphine: May decrease therapeutic effects of Opioid Agonists. Management: Seek alternatives to buprenorphine in patients receiving pure opioid agonists. If combined in certain pain management situations (eg, surgery), monitor for symptoms of therapeutic failure/high dose requirements or opioid withdrawal symptoms. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects 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 increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CNS Depressants: May increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists 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
CNS Depressants: May increase CNS depressant effects 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
CYP2D6 Inhibitors (Strong): May increase serum concentration of OxyCODONE. CYP2D6 Inhibitors (Strong) may decrease active metabolite exposure of OxyCODONE. Specifically, oxymorphone concentrations may be reduced. Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of OxyCODONE. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of OxyCODONE. Risk C: Monitor
CYP3A4 Inhibitors (Moderate): May increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase adverse/toxic effects of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor
Daridorexant: May increase CNS depressant effects 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 increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Diuretics: Opioid Agonists may increase adverse/toxic effects of Diuretics. Opioid Agonists may decrease therapeutic effects of Diuretics. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
DroPERidol: May increase CNS depressant effects 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 increase constipating effects of Eluxadoline. Risk X: Avoid
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects 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 serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Gastrointestinal Agents (Prokinetic): Opioid Agonists may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Grapefruit Juice: May increase active metabolite exposure of OxyCODONE. Specifically, concentrations of oxymorphone may be increased. Grapefruit Juice may increase serum concentration of OxyCODONE. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects 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
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): May decrease therapeutic effects of Opioid Agonists. Opioid Agonists may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects 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
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects 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 increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Monoamine Oxidase Inhibitors: OxyCODONE may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Use of oxycodone is not recommended for patients taking MAOIs or within 14 days of MAOI discontinuation. If combined, use test doses and frequent titration of small doses while monitoring blood pressure, CNS depression, and signs of serotonin syndrome. Risk D: Consider Therapy Modification
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalmefene: May decrease therapeutic effects 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 decrease therapeutic effects of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk X: Avoid
Nefazodone: Opioid Agonists (metabolized by CYP3A4) may increase serotonergic effects of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase 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
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists 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
Opioids (Mixed Agonist / Antagonist): May decrease analgesic effects 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
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Pegvisomant: Opioid Agonists may decrease therapeutic effects of Pegvisomant. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
PHENobarbital: May increase CNS depressant effects of OxyCODONE. PHENobarbital may decrease serum concentration of OxyCODONE. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a moderate CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider Therapy Modification
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Primidone: May increase CNS depressant effects of OxyCODONE. Primidone may decrease serum concentration of OxyCODONE. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a moderate CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider Therapy Modification
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ramosetron: Opioid Agonists may increase constipating effects of Ramosetron. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects 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 increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Samidorphan: May decrease therapeutic effects of Opioid Agonists. Risk X: Avoid
Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): OxyCODONE may increase serotonergic effects of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase serum concentration of OxyCODONE. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may decrease active metabolite exposure of OxyCODONE. Specifically, oxymorphone concentrations may be reduced. Risk C: Monitor
Serotonergic Agents (High Risk): OxyCODONE may increase serotonergic effects 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
Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects 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 decrease analgesic effects of Somatostatin Analogs. Opioid Agonists may increase analgesic effects of Somatostatin Analogs. Risk C: Monitor
Succinylcholine: May increase bradycardic effects of Opioid Agonists. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of Thalidomide. Risk X: Avoid
Tilidine: May increase therapeutic effects of Opioid Agonists. Risk X: Avoid
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects 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
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Chronic opioid use may cause hypogonadism and hyperprolactinemia which may decrease fertility in patients of reproductive potential. Menstrual cycle disorders (including amenorrhea), erectile dysfunction, and impotence have been reported. The incidence of hypogonadism may be increased with the use of opioids in high doses or long-acting opioid formulations. It is not known if the effects on fertility are reversible. Monitor patients on long-term therapy (de Vries 2020; Gadelha 2022).
Consider family planning, contraception, and the effects on fertility prior to prescribing opioids for chronic pain to patients who could become pregnant (ACOG 2017; CDC [Dowell 2022]).
Oxycodone crosses the placenta (Kokki 2012).
Maternal use of opioids may be associated with poor fetal growth, stillbirth, and preterm delivery (CDC [Dowell 2022]). Opioids used as part of obstetric analgesia/anesthesia during labor and delivery may temporarily affect the fetal heart rate (ACOG 2019).
Neonatal abstinence syndrome (NAS)/neonatal opioid withdrawal syndrome (NOWS) may occur following prolonged in utero exposure to opioids (CDC [Dowell 2022]). NAS/NOWS may be life-threatening if not recognized and treated and requires management according to protocols developed by neonatology experts. Presentation of symptoms varies by opioid characteristics (eg, immediate release, sustained release), time of last dose prior to delivery, drug metabolism (maternal, placental, and infant), net placental transfer, as well as other factors (AAP [Hudak 2012]; AAP [Patrick 2020]). Clinical signs characteristic of withdrawal following in utero opioid exposure include excessive crying or easily irritable, fragmented sleep (<2 to 3 hours after feeding), tremors, increased muscle tone, or GI dysfunction (hyperphagia, poor feeding, feeding intolerance, watery or loose stools) (Jilani 2022). NAS/NOWS occurs following chronic opioid exposure and would not be expected following the use of opioids at delivery (AAP [Patrick 2020]).
Monitor infants of mothers on long-term/chronic opioid therapy for symptoms of withdrawal. Symptom onset reflects the half-life of the opioid used. Monitor infants for at least 3 days following exposure to immediate-release opioids; monitor for at least 4 to 7 days following exposure to sustained-release opioids (AAP [Patrick 2020]; CDC [Dowell 2022]). Monitor newborns for excess sedation and respiratory depression when opioids are used during labor.
When opioids are needed to treat acute pain in pregnant patients, the lowest effective dose for only the expected duration of pain should be prescribed (CDC [Dowell 2022]).
Opioid use for pain following vaginal or cesarean delivery should be made as part of a shared decision-making process. A stepwise, multimodal approach to managing postpartum pain is recommended. A low-dose, low-potency, short-acting opioid such as oxycodone can be used to treat acute pain associated with delivery when needed (ACOG 2021).
Opioids are not preferred for the treatment of chronic noncancer pain during pregnancy; consider strategies to minimize or avoid opioid use. Advise pregnant patients requiring long-term opioid use of the risk of NAS/NOWS and provide appropriate treatment for the neonate after delivery. NAS/NOWS is an expected and treatable condition following chronic opioid use during pregnancy and should not be the only reason to avoid treating pain with an opioid in pregnant patients (ACOG 2017; CDC [Dowell 2022]). Do not abruptly discontinue opioids during pregnancy; taper prior to discontinuation when appropriate, considering the risks to the pregnant patient and fetus if maternal withdrawal occurs (CDC [Dowell 2022]).
Oxycodone is present in breast milk.
Multiple reports summarize data related to the presence of oxycodone in breast milk:
• Oxycodone is present in breast milk in variable concentrations following postpartum administration of oral oxycodone in combination with acetaminophen (Marx 1986). Breast milk concentrations of oxycodone were higher than those in the maternal plasma in multiple studies (Marx 1986; Pesonen 2024; Seaton 2007).
• Oxycodone was detected in the breast milk of lactating patients administered sustained-release oxycodone 10 mg/naloxone 5 mg twice daily (n=21) or oxycodone 10 mg twice daily (n=22) for up to 3 days following cesarean delivery. The highest breast milk concentrations were obtained 170 minutes following the dose, and the lowest breast milk concentrations were found 38 to 40 hours after the scheduled dose. Patients also received supplemental oxycodone (IV, oral, or SUBQ) as part of multimodal pain management. Noroxycodone was the main metabolite detected in breast milk; concentrations of oxymorphone and noroxymorphone could not be determined (Pesonen 2024).
• Breast milk was sampled in 50 patients administered oral oxycodone 10 mg every 2 hours as needed following cesarean delivery. Patients also received rectal oxycodone 30 mg at the end of surgery. Breast milk and maternal serum were sampled 24, 48, and 72 hours after delivery. Neonatal plasma was sampled ~48 and 72 hours after birth. Oxycodone was measurable in breast milk up to 37 hours after the last maternal dose. Therapeutic concentrations (7.4 ng/mL) were detected in the serum of 1 breastfeeding infant. Breast milk concentrations of oxycodone correlated with those in the maternal plasma (Seaton 2007).
• Oxycodone was also detected in the urine of a 45-day-old exclusively breastfed infant. The mother was taking oral oxycodone 5 to 10 mg every 4 to 6 hours for episiotomy pain. Adverse events were observed in the 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).
Nonopioid analgesics are preferred for lactating patients who require pain control peripartum or for surgery outside of the postpartum period. When opioids are needed for lactating patients, use the lowest effective dose for the shortest duration of time to limit adverse events in the mother and breastfeeding infant (AAP [Sachs 2013]; ABM [Martin 2018]; ABM [Reece-Stremtan 2017]). When an opiate is needed, use of oxycodone in breastfeeding patients is not recommended by some guidelines (AAP [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 2019).
When chronic opioids are prescribed prenatally and continued postpartum, breastfeeding may be initiated to help mitigate potential newborn withdrawal; monitor both the mother and the infant (AAP [Meek 2022]; AAP [Patrick 2020]).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Monitor infants exposed to opioids via breast milk for drowsiness, sedation, feeding difficulties, or limpness (ACOG 2019). Withdrawal symptoms may occur when maternal use is discontinued, or breastfeeding is stopped.
Instruct patient to avoid high-fat meals when taking some products (food has no effect on the reformulated OxyContin).
Pain relief, respiratory and mental status, blood pressure; bowel function; signs/symptoms of misuse, abuse, and substance use disorder; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013)
Alternate recommendations: Subacute or 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. In patients with subacute pain initially treated for acute pain, reassess pain and function after 30 days to address potentially reversible causes of pain and prevent unintentional long-term opioid therapy. In patients on long-term therapy, re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Toxicology testing is recommended prior to initiation and at least yearly (includes controlled prescription medications, illicit drugs of abuse, and benzodiazepines). 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) (CDC [Dowell 2022]).
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
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.
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).
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: Bioavailability increased by 50% to 95% (Christian-Miller 2018). 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.
