The FDA has issued a drug safety communication to announce safety-related updates to the prescribing information for immediate-release (IR) and extended-release (ER)/long-acting (LA) opioid analgesics, including updates to Boxed Warnings, Indications and Usage, Dosage and Administration, Warnings and Precautions, and the Medication Guide. These safety labeling changes are intended to provide clarity on appropriate patient populations for opioid treatment, appropriate dosage and administration, and updated information on the risks associated with opioid use. The required safety labeling changes include stating:
the risk of overdose increases as the dosage increases for all opioid pain medicines;
IR opioids should not be used for an extended period of time unless a patient's pain remains severe enough to require them and alternative treatment options continue to be inadequate;
many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine;
it is recommended to reserve ER/LA opioid pain medicines for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate; and
a warning about opioid-induced hyperalgesia (OIH), including information on differentiating OIH symptoms from those of opioid tolerance and withdrawal.
Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-prescribing-information-all-opioid-pain-medicines-provide-additional-guidance-safe-use.
Oxycodone exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing oxycodone and monitor all patients regularly for the development of these behaviors or conditions.
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the FDA has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are strongly encouraged to complete a REMS-compliant education program and counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety.
Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone. Monitor for respiratory depression, especially during initiation of oxycodone or following a dose increase. Instruct patients to swallow oxycodone tablets whole; crushing, chewing, or dissolving oxycodone ER tablets can cause rapid release and absorption of a potentially fatal dose of oxycodone.
Accidental ingestion of even one dose of oxycodone, especially by children, can result in a fatal overdose of oxycodone.
Prolonged use of oxycodone during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
The concomitant use of oxycodone with all cytochrome P450 (CYP-450) 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used CYP3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving oxycodone and any CYP3A4 inhibitor or inducer.
Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of oxycodone and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
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.
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:
Analgesia, moderate to severe pain: Limited data available:
Infants ≤6 months: Immediate release: Oral solution (1 mg/mL): Oral: Initial dose: 0.025 to 0.05 mg/kg/dose every 4 to 6 hours as needed (Ref).
Infants >6 months, Children, and Adolescents:
Patient weight <50 kg: Immediate release: Oral: Initial dose: 0.1 to 0.2 mg/kg/dose every 4 to 6 hours as needed; for severe pain some experts have recommended an initial dose of 0.2 mg/kg; usual maximum dose range: 5 to 10 mg/dose (Ref).
Patient weight ≥50 kg: Immediate release: Oral: Initial dose: 5 to 10 mg every 4 to 6 hours as needed; for severe pain an initial dose of 10 mg may be used; usual maximum dose: 20 mg/dose (Ref).
Analgesia, severe pain requiring around-the-clock long-term opioid therapy: 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.
(For additional information see "Oxycodone: Drug information")
Dosage guidance:
Safety: Consider prescribing naloxone 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 [equivalent to oxycodone ≥33 mg/day]), 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. Do not use long-acting preparations for treatment of acute pain (Ref).
Immediate release:
Oral: Initial: 5 mg every 4 to 6 hours as needed; adjust dose according to patient response. Usual dosage range: 5 to 15 mg every 4 to 6 hours as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies. For outpatient use, usually up to 20 mg/day for moderate pain or up to 30 mg/day for severe pain will suffice. Dosing is based on severity of pain and patient-specific factors; reduced dosing may be indicated in patients with comorbidities (Ref).
Rectal [Canadian product]: Usual dosage range: One (10 or 20 mg) suppository up to 3 to 4 times daily as needed. If usual dose and frequency is insufficient, reassess patient and reconsider pain management strategies (Ref).
Acute pain (eg, breakthrough cancer pain) in patients on chronic opioid therapy:
Immediate release: Oral: Usual dose: In conjunction with the scheduled opioid, administer 5% to 15% (rarely up to 20%) of the 24-hour oxycodone requirement (or MME) as needed using an IR formulation every 4 to 6 hours with subsequent dosage adjustments based upon response (Ref). Note: If chronic opioid is not oxycodone, use MME calculations cautiously due to lack of complete cross-tolerance; generally, reduce calculated dose by 25% to 50%; conversions from methadone are highly variable and require extreme caution (Ref).
Acute postoperative pain, postoperative recovery/postanesthesia care unit :
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 (equivalent to oxycodone ≥33 mg/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 (equivalent to oxycodone ≥33 mg/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 (equivalent to oxycodone ≥33 mg/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 (equivalent to oxycodone ≥33 mg/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. 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.
Immediate release: Initiate therapy at 33% to 50% the usual dosage and titrate carefully. For patients with severe impairment, consider extending the dosing interval based on response and tolerability (eg, every 6 to 12 hours) (Ref).
Extended release tablets or Extended release capsules: Initial: Initiate oxycodone ER with 33% to 50% of the calculated recommended dose. If reduced dose is less than smallest available dosage form consider alternative analgesic.
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, drug dependence, hyperalgesia, mood changes, neonatal withdrawal, 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).
• 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; oxycodone clearance may decrease.
• Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to 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 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 access: Discuss the availability of naloxone with all patients who are prescribed opioid analgesics, as well as their caregivers, and consider prescribing it to patients who are at increased risk of opioid overdose. These include patients who are also taking benzodiazepines or other CNS depressants, have an opioid use disorder (OUD) (current or history of), or have experienced opioid-induced respiratory depression/opioid overdose. Additionally, health care providers should consider prescribing naloxone to patients prescribed medications to treat OUD; patients at risk of opioid overdose even if they are not taking an opioid analgesic or medication to treat OUD; and patients taking opioids, including methadone or buprenorphine for OUD, if they have household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose. Inform patients and caregivers on options for obtaining naloxone (eg, by prescription, directly from a pharmacist, a community-based program) as permitted by state dispensing and prescribing guidelines. Educate patients and caregivers on how to recognize respiratory depression, proper administration of naloxone, and getting emergency help.
• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.
• REMS program: To ensure that the benefits of opioid analgesics outweigh the risks of substance use disorder, abuse, and misuse, a REMS is required. Drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are encouraged to complete a REMS-compliant education program; counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist; and consider other tools to improve patient, household, and community safety.
• Surgery: Opioids decrease bowel motility; monitor for decreased bowel motility in 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, 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:
RoxyBond: 15 mg, 30 mg [contains fd&c blue #2 (indigotine,indigo carmine)]
Tablet Abuse-Deterrent, Oral, as hydrochloride:
RoxyBond: 5 mg
Tablet ER 12 Hour Abuse-Deterrent, Oral, as hydrochloride:
OxyCONTIN: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg
OxyCONTIN: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Generic: 10 mg, 15 mg [DSC], 20 mg, 30 mg [DSC], 40 mg, 60 mg [DSC], 80 mg
May be product dependent
Capsule ER 12 Hour Abuse-Deterrent (Xtampza ER Oral)
9 mg (per each): $7.65
13.5 mg (per each): $11.26
18 mg (per each): $14.28
27 mg (per each): $19.86
36 mg (per each): $24.44
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 (RoxyBond Oral)
5 mg (per each): $15.28
15 mg (per each): $18.84
30 mg (per each): $25.40
Tablet ER 12 Hour Abuse-Deterrent (oxyCODONE HCl ER Oral)
10 mg (per each): $4.23 - $5.03
20 mg (per each): $7.88 - $9.37
40 mg (per each): $13.10 - $16.05
80 mg (per each): $28.01
Tablet ER 12 Hour Abuse-Deterrent (OxyCONTIN Oral)
10 mg (per each): $6.57
15 mg (per each): $9.66
20 mg (per each): $12.24
30 mg (per each): $17.03
40 mg (per each): $20.95
60 mg (per each): $29.68
80 mg (per each): $36.58
Tablets (Oxaydo Oral)
5 mg (per each): $12.86
7.5 mg (per each): $19.26
Tablets (oxyCODONE HCl Oral)
5 mg (per each): $0.08 - $0.62
10 mg (per each): $0.15 - $1.45
15 mg (per each): $0.12 - $2.37
20 mg (per each): $0.27 - $2.32
30 mg (per each): $0.18 - $4.49
Tablets (Roxicodone Oral)
15 mg (per each): $6.23
30 mg (per each): $12.23
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suppository, Rectal:
Supeudol 10: 10 mg (12 ea)
Supeudol 20: 20 mg (12 ea)
Tablet, Oral, as hydrochloride:
Oxy-IR: 5 mg, 10 mg, 20 mg
Supeudol: 5 mg, 10 mg, 20 mg
Generic: 5 mg, 10 mg, 20 mg
Tablet ER 12 Hour Abuse-Deterrent, Oral, as hydrochloride:
OxyNEO: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg
OxyNEO: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Tablet Extended Release 12 Hour, Oral:
Generic: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, 80 mg
OxyContin tablets deliver medication over 12 hours; release is pH independent. Equianalgesic doses: oral oxycodone 30 mg = morphine 10 mg IM = single oral dose morphine 60 mg or chronic dosing oral morphine 30 mg. Note: Not appropriate for OxyContin initial dose calculation.
Oxaydo utilizes Acura Pharmaceutical's Aversion technology which may help discourage misuse and abuse potential. Reduced abuse potential of Oxaydo compared to other immediate-release oxycodone tablet formulations has not been proven; the FDA has required a post-approval epidemiological study to determine whether the formulation actually results in a decrease of misuse/abuse. In one clinical trial in nondependent recreational opioid users, the "drug-liking" responses and safety of crushed Oxaydo tablets were compared to crushed immediate-release oxycodone tablets following the self-administered intranasal use. A small difference in "drug-liking" scores was observed, with lower scores reported in the crushed Oxaydo group. In regard to safety, there was an increased incidence of nasopharyngeal and facial adverse events in the Oxaydo group. In addition, there was decreased ability in the Oxaydo group to completely administer the 2 crushed Oxaydo tablets intranasally within a set time period. However, whether these differences translate into a significant clinical difference is unknown. Of note, pharmacokinetic studies showed that Oxaydo is bioequivalent with oxycodone immediate-release tablets with no differences in Tmax and half-life when administered in the fasted state.
C-II
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.
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.
Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from light and moisture.
Suppository [Canadian product]: Store below 25°C (77°F).
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/2021/202080s012lbl.pdf#page=30
Oxycodone hydrochloride capsules: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/200534s013lbl.pdf#page=32
Oxycodone hydrochloride oral solution: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/201194s009lbl.pdf#page=33
OxyContin: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022272s048lbl.pdf#page=49
Roxybond: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/209777s007lbl.pdf#page=39
Roxicodone: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021011s013lbl.pdf#page=30
Xtampza ER: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208090s015lbl.pdf#page=39
Immediate-release formulations (capsules, oral solution, and tablets [eg, Oxaydo, RoxyBond, Roxicodone]): Management of acute or chronic moderate to severe pain for which the use of an opioid analgesic is appropriate and alternative treatments are inadequate (FDA approved in adults).
Extended-release capsule (Xtampza ER): Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate (FDA approved in adults).
Extended-release tablets (eg, OxyContin): Management of pain severe enough to require daily, around-the-clock, long-term opioid therapy for which alternative treatment options are inadequate in adults and also opioid-tolerant in pediatric patients (FDA approved in pediatric patients ≥11 years receiving and tolerating ≥20 mg/day oxycodone or its equivalent and adults).
Limitations of use: Reserve oxycodone for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Oxycodone ER is not indicated as an as-needed analgesic.
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 which have a heightened risk of causing significant patient harm when used in error.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Alvimopan: Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification
Amphetamines: May enhance the analgesic effect of Opioid Agonists. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CNS Depressants: May enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
CYP3A4 Inducers (Moderate): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of OxyCODONE. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite Oxymorphone may also be increased. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May enhance the adverse/toxic effect of OxyCODONE. CYP3A4 Inhibitors (Strong) may increase the serum concentration of OxyCODONE. Serum concentrations of the active metabolite oxymorphone may also be increased. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Desmopressin: Opioid Agonists may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Eluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Gastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: OxyCODONE may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. 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
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: Consider therapy modification
Naltrexone: May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk X: Avoid combination
Nefazodone: Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4). Management: If concomitant use of opioid agonists that are metabolized by CYP3A4 and nefazodone is necessary, consider dose reduction of the opioid until stable drug effects are achieved. Monitor for increased opioid effects and serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk X: Avoid combination
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Pegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
PHENobarbital: May enhance the CNS depressant effect of OxyCODONE. PHENobarbital may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider therapy modification
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Primidone: May enhance the CNS depressant effect of OxyCODONE. Primidone may decrease the serum concentration of OxyCODONE. Management: Avoid use of oxycodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased oxycodone efficacy and withdrawal if combined. Risk D: Consider therapy modification
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ramosetron: Opioid Agonists may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Samidorphan: May diminish the therapeutic effect of Opioid Agonists. Risk X: Avoid combination
Serotonergic Agents (High Risk): Opioid Agonists (metabolized by CYP3A4) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Somatostatin Analogs: Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect 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
Instruct patient to avoid high-fat meals when taking some products (food has no effect on the reformulated OxyContin).
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]).
Acute pain (short-term): Pain relief, respiratory rate, mental status, blood pressure; stool output; signs of misuse, abuse, and substance use disorder.
Chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. Reevaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and with consideration for rechecking at least yearly (includes controlled prescription medications and illicit drugs of abuse). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (CDC [Dowell 2016]).
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.
Adults with CrCl <60 mL/minute: Half-life increases by 1 hour, but peak oxycodone concentrations increase by 50% and AUC increases by 60%.
Adults with mild to moderate hepatic impairment: Half-life increases by 2.3 hours, peak oxycodone concentrations increase by 50%, and AUC increases by 95%.
Time to peak, plasma: Immediate release: 1.2 to 1.9 hours; Extended release: 4 to 5 hours.
Excretion: Urine: (~10% as parent; ~65% as metabolites [noroxycodone (23%, active), oxymorphone (10%, active), noroxymorphone (14%, weakly active), reduced metabolites (≤18%)]) (Kinnunen 2019).
Altered kidney function: Higher peak plasma oxycodone (50%), and noroxycodone (20%), higher AUC for oxycodone (60%), noroxycodone (50%), and oxymorphone (40%) in patients with CrCl <60 mL/minute. There is an increased half-life elimination for oxycodone elimination of only 1 hour.
Hepatic function impairment: Peak plasma oxycodone and noroxycodone concentrations 50% and 20% higher; AUC values are 95% and 65% higher, respectively, in mild to moderate hepatic impairment. Oxymorphone peak plasma concentration and AUC values are lower by 30% and 40%. The half-life elimination for oxycodone is increased by 2.3 hours.
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