oxycodone/acetaminophen (Rx)

Brand and Other Names:Percocet, Primlev, more...Roxicet, Endocet, Xartemis XR
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

oxycodone/acetaminophen

tablet: Schedule II

  • 2.5mg/325mg
  • 5mg/300mg; 5mg/325mg
  • 7.5mg/300mg; 7.5mg/325mg
  • 10mg/300mg; 10mg/325mg

oral solution: Schedule II

  • (5mg/325mg)/5mL

tablet, extended release: Schedule II

  • 7.5mg/325mg (Xartemis XR)

Acute Pain

Indicated for management of acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate

Extended-release tablet (Xartemis XR): 2 tab PO q12hr without regard to food

The second dose of 2 tablets may be administered as early as 8 hr after the initial dose if analgesia required at that time; subsequent doses are to be administered 2 tablets q12hr

Not to exceed total 4 g/day of acetaminophen (total daily dose from any source)

Moderate-to-Severe Pain

2.5 mg/325 mg: 1-2 tablets PO q6hr

5 mg/325 mg, 7.5 mg/500 mg, 10 mg/650 mg: 1 tablet PO q6hr

Not to exceed total 4 g/day of acetaminophen (total daily dose from any source)

Chronic pain: Administer as scheduled dosing around the clock

Intermittent or breakthrough pain: Administer as needed

Dosage Modifications

Hepatic impairment: Reduce dose in cases of severe impairment

Renal impairment: Elimination half-life prolonged with end-stage renal impairment; dose reduction may be required

Dosing Considerations

Adjust dose according to severity of pain and patient response

Extended-release (Xartemis XR) is a bilayer formulation of oxycodone and acetaminophen (contains immediate- and extended-release layers) which is not interchangeable with other oxycodone/acetaminophen products because of differing pharmacokinetic profiles

Access to naloxone for opioid overdose

  • Assess need for naloxone upon initiating and renewing treatment
  • Consider prescribing naloxone
    • Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
    • Household members (including children) or other close contacts at risk for accidental ingestion or overdose
  • Consult patients and caregivers on the following:
    • Availability of naloxone for emergency treatment of opioid overdose
    • Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)

Dosage Forms & Strengths

tablet: Schedule II

  • 2.5mg/325mg
  • 5mg/300mg; 5mg/325mg
  • 7.5mg/300mg; 7.5mg/325mg
  • 10mg/300mg; 10mg/325mg

oral solution: Schedule II

  • (5mg/325mg)/5mL

Pain (Off-Label)

Initial dose

  • Initial dose based on oxycodone component
  • Moderate pain: 0.05-0.1 mg/kg/dose PO q4-6hr PRN  
  • Severe pain: 0.3 mg/kg/dose PO q6hr

Maximum dose

  • Maximum dose based on acetaminophen component
  • <45 kg: Not to exceed acetaminophen 90 mg/kg/day PO
  • >45 kg: Not to exceed acetaminophen 4 g/day PO

Dosage Modifications

Hepatic impairment: Reduce dose in cases of severe impairment

Renal impairment: Elimination half-life prolonged with end-stage renal impairment; dose reduction may be required

Dosing Considerations

Adjust dose according to pain severity and patient response

In cases of severe pain or if tolerant to the analgesic effects, a higher dose may be required

For chronic pain, administer scheduled doses around-the-clock; otherwise may take as needed for intermittent pain

Discontinuation: Opioid tolerance may occur; gradually taper dose when discontinuing if treated for more than a few weeks

Access to naloxone for opioid overdose

  • Assess need for naloxone upon initiating and renewing treatment
  • Consider prescribing naloxone
    • Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
    • Household members (including children) or other close contacts at risk for accidental ingestion or overdose
  • Consult patients and caregivers on the following:
    • Availability of naloxone for emergency treatment of opioid overdose
    • Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)
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Interactions

Interaction Checker

and oxycodone/acetaminophen

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    Contraindicated

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            Contraindicated (1)

            • alvimopan

              alvimopan, oxycodone. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

            Serious - Use Alternative (52)

            • abametapir

              abametapir will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • amobarbital

              amobarbital will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • atazanavir

              atazanavir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • bremelanotide

              bremelanotide will decrease the level or effect of oxycodone by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

            • buprenorphine

              buprenorphine, oxycodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • buprenorphine buccal

              buprenorphine buccal, oxycodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • butorphanol

              butorphanol, oxycodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • calcium/magnesium/potassium/sodium oxybates

              oxycodone, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • cimetidine

              cimetidine increases effects of oxycodone by decreasing metabolism. Avoid or Use Alternate Drug.

            • clarithromycin

              clarithromycin increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • clonidine

              clonidine, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

            • conivaptan

              conivaptan increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • diazepam intranasal

              diazepam intranasal, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • eluxadoline

              oxycodone, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

            • eszopiclone

              eszopiclone and oxycodone both increase sedation. Avoid or Use Alternate Drug. Additive CNS depression may lead to hypotension, profound sedation, respiratory depression, or coma

            • fentanyl

              fentanyl, oxycodone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl intranasal

              fentanyl intranasal, oxycodone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl transdermal

              fentanyl transdermal, oxycodone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fentanyl transmucosal

              fentanyl transmucosal, oxycodone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

            • fluoxetine

              oxycodone will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Opioids may enhance the serotonergic effects of SSRIs and increase risk for serotonergic syndrome

            • fosamprenavir

              fosamprenavir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors .

            • grapefruit

              grapefruit will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • hydrocodone

              hydrocodone, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • idelalisib

              idelalisib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • imatinib

              imatinib increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • indinavir

              indinavir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • isocarboxazid

              isocarboxazid increases toxicity of oxycodone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • isoniazid

              isoniazid increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • ivosidenib

              ivosidenib will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ketoconazole

              ketoconazole increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • linezolid

              linezolid increases toxicity of oxycodone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • lonafarnib

              acetaminophen will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

            • lopinavir

              lopinavir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • lumefantrine

              lumefantrine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • methylene blue

              methylene blue and oxycodone both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • metoclopramide intranasal

              oxycodone, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • nalbuphine

              nalbuphine, oxycodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • nefazodone

              nefazodone increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • nelfinavir

              nelfinavir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • nicardipine

              nicardipine increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • ozanimod

              ozanimod and oxycodone both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • paroxetine

              paroxetine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • pentazocine

              pentazocine, oxycodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • pexidartinib

              acetaminophen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

            • phenelzine

              phenelzine increases toxicity of oxycodone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • posaconazole

              posaconazole increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • prasugrel

              oxycodone will decrease the level or effect of prasugrel by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of prasugrel and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

            • pretomanid

              acetaminophen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

            • procarbazine

              procarbazine increases toxicity of oxycodone by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .

            Monitor Closely (273)

            • albuterol

              oxycodone increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alfentanil

              alfentanil and oxycodone both increase sedation. Use Caution/Monitor.

            • alprazolam

              alprazolam and oxycodone both increase sedation. Use Caution/Monitor.

            • amiodarone

              amiodarone will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • amitriptyline

              oxycodone and amitriptyline both increase sedation. Use Caution/Monitor.

            • amobarbital

              amobarbital and oxycodone both increase sedation. Use Caution/Monitor.

            • amoxapine

              oxycodone and amoxapine both increase sedation. Use Caution/Monitor.

            • apalutamide

              apalutamide will decrease the level or effect of acetaminophen by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

            • apomorphine

              oxycodone and apomorphine both increase sedation. Use Caution/Monitor.

            • arformoterol

              oxycodone increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aripiprazole

              oxycodone and aripiprazole both increase sedation. Use Caution/Monitor.

            • armodafinil

              oxycodone increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • asenapine

              asenapine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • atracurium

              oxycodone increases effects of atracurium by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Oxycodone may enhance the neuromuscular blocking action of true skeletal muscle relaxants and produce an increased degree of respiratory depression.

            • avapritinib

              acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • axitinib

              acetaminophen increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • azelastine

              azelastine and oxycodone both increase sedation. Use Caution/Monitor.

            • baclofen

              baclofen and oxycodone both increase sedation. Use Caution/Monitor.

            • belladonna and opium

              belladonna and opium and oxycodone both increase sedation. Use Caution/Monitor.

            • benperidol

              oxycodone and benperidol both increase sedation. Use Caution/Monitor.

            • benzphetamine

              oxycodone increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • bosentan

              bosentan decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brexanolone

              brexanolone, oxycodone. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • brompheniramine

              brompheniramine and oxycodone both increase sedation. Use Caution/Monitor.

            • bupivacaine implant

              acetaminophen, bupivacaine implant. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Local anesthetics may increase the risk of developing methemoglobinemia when concurrently exposed to drugs that also cause methemoglobinemia.

            • buprenorphine

              buprenorphine and oxycodone both increase sedation. Use Caution/Monitor.

            • buprenorphine buccal

              buprenorphine buccal and oxycodone both increase sedation. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              oxycodone increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

            • bupropion

              bupropion will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • busulfan

              acetaminophen increases levels of busulfan by decreasing metabolism. Use Caution/Monitor. Use of acetaminophen prior to (< 72 hours) or concurrently with busulfan may result in decreased clearance of busulfan due to acetaminophen-induced decreases in glutathione levels.

            • butabarbital

              butabarbital and oxycodone both increase sedation. Use Caution/Monitor.

            • butalbital

              butalbital and oxycodone both increase sedation. Use Caution/Monitor.

            • butorphanol

              butorphanol and oxycodone both increase sedation. Use Caution/Monitor.

            • caffeine

              oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carbamazepine

              carbamazepine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • carbinoxamine

              carbinoxamine and oxycodone both increase sedation. Use Caution/Monitor.

            • carisoprodol

              carisoprodol and oxycodone both increase sedation. Use Caution/Monitor.

            • celecoxib

              celecoxib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • cenobamate

              cenobamate will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

              cenobamate, oxycodone. Either increases effects of the other by sedation. Use Caution/Monitor.

            • chloral hydrate

              chloral hydrate and oxycodone both increase sedation. Use Caution/Monitor.

            • chloramphenicol

              chloramphenicol will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chlordiazepoxide

              chlordiazepoxide and oxycodone both increase sedation. Use Caution/Monitor.

            • chloroquine

              chloroquine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine and oxycodone both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              oxycodone and chlorpromazine both increase sedation. Use Caution/Monitor.

            • chlorzoxazone

              chlorzoxazone and oxycodone both increase sedation. Use Caution/Monitor.

            • cimetidine

              cimetidine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • cinnarizine

              cinnarizine and oxycodone both increase sedation. Use Caution/Monitor.

            • cisatracurium

              oxycodone increases effects of cisatracurium by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Oxycodone may enhance the neuromuscular blocking action of true skeletal muscle relaxants and produce an increased degree of respiratory depression.

            • citalopram

              oxycodone increases effects of citalopram by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Opioids may enhance the serotonergic effects of SSRIs and increase risk for serotonergic syndrome.

            • clemastine

              clemastine and oxycodone both increase sedation. Use Caution/Monitor.

            • clobazam

              oxycodone, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clomipramine

              oxycodone and clomipramine both increase sedation. Use Caution/Monitor.

            • clonazepam

              clonazepam and oxycodone both increase sedation. Use Caution/Monitor.

            • clorazepate

              clorazepate and oxycodone both increase sedation. Use Caution/Monitor.

            • clozapine

              oxycodone and clozapine both increase sedation. Use Caution/Monitor.

            • cobicistat

              cobicistat will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • codeine

              codeine and oxycodone both increase sedation. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • crofelemer

              crofelemer increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclizine

              cyclizine and oxycodone both increase sedation. Use Caution/Monitor.

            • cyclobenzaprine

              cyclobenzaprine and oxycodone both increase sedation. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine and oxycodone both increase sedation. Use Caution/Monitor.

            • dabrafenib

              dabrafenib decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dantrolene

              dantrolene and oxycodone both increase sedation. Use Caution/Monitor.

            • dapsone topical

              acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

            • darifenacin

              darifenacin will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • darunavir

              darunavir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • desflurane

              desflurane and oxycodone both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

            • desipramine

              oxycodone and desipramine both increase sedation. Use Caution/Monitor.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • deutetrabenazine

              oxycodone and deutetrabenazine both increase sedation. Use Caution/Monitor.

            • dexamethasone

              dexamethasone decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dexchlorpheniramine

              dexchlorpheniramine and oxycodone both increase sedation. Use Caution/Monitor.

            • dexfenfluramine

              oxycodone increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexmedetomidine

              dexmedetomidine and oxycodone both increase sedation. Use Caution/Monitor.

            • dexmethylphenidate

              oxycodone increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextroamphetamine

              oxycodone increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextromoramide

              dextromoramide and oxycodone both increase sedation. Use Caution/Monitor.

            • diamorphine

              diamorphine and oxycodone both increase sedation. Use Caution/Monitor.

            • diazepam

              diazepam and oxycodone both increase sedation. Use Caution/Monitor.

            • dichlorphenamide

              dichlorphenamide, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

            • diethylpropion

              oxycodone increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • difenoxin hcl

              difenoxin hcl and oxycodone both increase sedation. Use Caution/Monitor.

            • diltiazem

              diltiazem will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dimenhydrinate

              dimenhydrinate and oxycodone both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              diphenhydramine and oxycodone both increase sedation. Use Caution/Monitor.

            • diphenoxylate hcl

              diphenoxylate hcl and oxycodone both increase sedation. Use Caution/Monitor.

            • dipipanone

              dipipanone and oxycodone both increase sedation. Use Caution/Monitor.

            • dobutamine

              oxycodone increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopamine

              oxycodone increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopexamine

              oxycodone increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dosulepin

              oxycodone and dosulepin both increase sedation. Use Caution/Monitor.

            • doxepin

              oxycodone and doxepin both increase sedation. Use Caution/Monitor.

            • doxylamine

              doxylamine and oxycodone both increase sedation. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • droperidol

              oxycodone and droperidol both increase sedation. Use Caution/Monitor.

            • duloxetine

              duloxetine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • duvelisib

              duvelisib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • efavirenz

              efavirenz decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eltrombopag

              eltrombopag increases levels of acetaminophen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

              eltrombopag increases levels of oxycodone by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • exenatide injectable solution

              exenatide injectable solution will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

            • encorafenib

              encorafenib, oxycodone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • enzalutamide

              enzalutamide decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ephedrine

              oxycodone increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine

              oxycodone increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine racemic

              oxycodone increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • escitalopram

              oxycodone increases effects of escitalopram by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Opioids may enhance the serotonergic effects of SSRIs and increase risk for serotonergic syndrome.

            • esketamine intranasal

              esketamine intranasal, oxycodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estazolam

              estazolam and oxycodone both increase sedation. Use Caution/Monitor.

            • ethanol

              oxycodone and ethanol both increase sedation. Use Caution/Monitor.

            • etomidate

              etomidate and oxycodone both increase sedation. Use Caution/Monitor.

            • etravirine

              etravirine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • exenatide injectable suspension

              exenatide injectable suspension will decrease the level or effect of acetaminophen by unspecified interaction mechanism. Use Caution/Monitor. To avoid potential interaction, give acetaminophen at least 1 hour before or 4 hours after exenatide injection.

            • fedratinib

              fedratinib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenfluramine

              oxycodone increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • finerenone

              acetaminophen will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • flibanserin

              acetaminophen will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

              oxycodone and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

            • fluphenazine

              oxycodone and fluphenazine both increase sedation. Use Caution/Monitor.

            • imatinib

              imatinib decreases levels of acetaminophen by decreasing hepatic clearance. Modify Therapy/Monitor Closely. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation (Ki value of 58.5 micro-M) at therapeutic levels; avoid chronic acetaminophen therapy with imatinib; if occasional acetaminophen administered, do not exceed 1300 mg/day.

            • flurazepam

              flurazepam and oxycodone both increase sedation. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine and oxycodone both increase serotonin levels. Use Caution/Monitor.

            • formoterol

              oxycodone increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • gabapentin

              gabapentin, oxycodone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, oxycodone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • haloperidol

              haloperidol will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              oxycodone and haloperidol both increase sedation. Use Caution/Monitor.

            • hydromorphone

              hydromorphone and oxycodone both increase sedation. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and oxycodone both increase sedation. Use Caution/Monitor.

            • iloperidone

              oxycodone and iloperidone both increase sedation. Use Caution/Monitor.

              iloperidone increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imatinib

              imatinib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • imipramine

              oxycodone and imipramine both increase sedation. Use Caution/Monitor.

            • isoniazid

              isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.

            • isoproterenol

              oxycodone increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

              itraconazole increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • ivacaftor

              acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

            • ketamine

              ketamine and oxycodone both increase sedation. Use Caution/Monitor.

            • ketotifen, ophthalmic

              oxycodone and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

            • lasmiditan

              lasmiditan, oxycodone. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant, oxycodone. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

              acetaminophen will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

            • letermovir

              letermovir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of acetaminophen by unknown mechanism. Use Caution/Monitor.

              acetaminophen increases levels of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by decreasing hepatic clearance. Use Caution/Monitor. Coadministration of ascorbic acid and certain combined hormonal contraceptives (CHCs) containing EE may increase plasma EE concentrations, possibly by inhibition of conjugation.

            • levalbuterol

              oxycodone increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • levorphanol

              levorphanol and oxycodone both increase sedation. Use Caution/Monitor.

            • lisdexamfetamine

              oxycodone increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lixisenatide

              lixisenatide will decrease the level or effect of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. GLP1 agonists delay gastric emptying, which may affect absorption of concomitantly administered oral medications. No effects on acetaminophen Cmax and Tmax were observed when acetaminophen was administered 1 hr before lixisenatide. When administered 1 or 4 hr after lixisenatide, acetaminophen Cmax was decreased by 29% and 31% respectively and median Tmax was delayed by 2 and 1.75 hr, respectively.

            • lofepramine

              oxycodone and lofepramine both increase sedation. Use Caution/Monitor.

            • lofexidine

              oxycodone and lofexidine both increase sedation. Use Caution/Monitor.

            • lomitapide

              acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • loprazolam

              loprazolam and oxycodone both increase sedation. Use Caution/Monitor.

            • lorazepam

              lorazepam and oxycodone both increase sedation. Use Caution/Monitor.

            • lorlatinib

              lorlatinib will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lormetazepam

              lormetazepam and oxycodone both increase sedation. Use Caution/Monitor.

            • loxapine

              oxycodone and loxapine both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              oxycodone and loxapine inhaled both increase sedation. Use Caution/Monitor.

            • lurasidone

              lurasidone, oxycodone. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

              oxycodone and maprotiline both increase sedation. Use Caution/Monitor.

            • maraviroc

              maraviroc will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • marijuana

              marijuana will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              oxycodone and marijuana both increase sedation. Use Caution/Monitor.

            • melatonin

              oxycodone and melatonin both increase sedation. Use Caution/Monitor.

            • meperidine

              meperidine and oxycodone both increase sedation. Use Caution/Monitor.

            • meprobamate

              oxycodone and meprobamate both increase sedation. Use Caution/Monitor.

            • metaproterenol

              oxycodone increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaxalone

              metaxalone and oxycodone both increase sedation. Use Caution/Monitor.

            • methadone

              methadone and oxycodone both increase sedation. Use Caution/Monitor.

            • methamphetamine

              oxycodone increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methocarbamol

              methocarbamol and oxycodone both increase sedation. Use Caution/Monitor.

            • methylenedioxymethamphetamine

              oxycodone increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • midazolam

              midazolam and oxycodone both increase sedation. Use Caution/Monitor.

            • midazolam intranasal

              midazolam intranasal, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

              acetaminophen will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

            • midodrine

              oxycodone increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mipomersen

              mipomersen, acetaminophen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mifepristone

              mifepristone will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mirtazapine

              oxycodone and mirtazapine both increase sedation. Use Caution/Monitor.

            • mitotane

              mitotane decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • modafinil

              oxycodone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • morphine

              morphine and oxycodone both increase sedation. Use Caution/Monitor.

            • motherwort

              oxycodone and motherwort both increase sedation. Use Caution/Monitor.

            • moxonidine

              oxycodone and moxonidine both increase sedation. Use Caution/Monitor.

            • nabilone

              oxycodone and nabilone both increase sedation. Use Caution/Monitor.

            • nafcillin

              nafcillin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nalbuphine

              nalbuphine and oxycodone both increase sedation. Use Caution/Monitor.

            • nevirapine

              nevirapine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nilotinib

              nilotinib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • norepinephrine

              oxycodone increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nortriptyline

              oxycodone and nortriptyline both increase sedation. Use Caution/Monitor.

            • olanzapine

              oxycodone and olanzapine both increase sedation. Use Caution/Monitor.

            • oliceridine

              oliceridine, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • opium tincture

              opium tincture and oxycodone both increase sedation. Use Caution/Monitor.

            • orphenadrine

              orphenadrine and oxycodone both increase sedation. Use Caution/Monitor.

            • oxazepam

              oxazepam and oxycodone both increase sedation. Use Caution/Monitor.

            • oxcarbazepine

              oxcarbazepine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxymorphone

              oxycodone and oxymorphone both increase sedation. Use Caution/Monitor.

            • paliperidone

              oxycodone and paliperidone both increase sedation. Use Caution/Monitor.

            • pancuronium

              oxycodone increases effects of pancuronium by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Oxycodone may enhance the neuromuscular blocking action of true skeletal muscle relaxants and produce an increased degree of respiratory depression.

            • papaveretum

              oxycodone and papaveretum both increase sedation. Use Caution/Monitor.

            • papaverine

              oxycodone and papaverine both increase sedation. Use Caution/Monitor.

            • parecoxib

              parecoxib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • paroxetine

              oxycodone increases effects of paroxetine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Opioids may enhance the serotonergic effects of SSRIs and increase risk for serotonergic syndrome.

            • pegvisomant

              oxycodone decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

            • pentazocine

              oxycodone and pentazocine both increase sedation. Use Caution/Monitor.

            • pentobarbital

              pentobarbital and oxycodone both increase sedation. Use Caution/Monitor.

              pentobarbital decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • perampanel

              perampanel and oxycodone both decrease sedation. Use Caution/Monitor.

            • perphenazine

              perphenazine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              oxycodone and perphenazine both increase sedation. Use Caution/Monitor.

            • phendimetrazine

              oxycodone increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenobarbital

              phenobarbital and oxycodone both increase sedation. Use Caution/Monitor.

              phenobarbital decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • phentermine

              oxycodone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine

              oxycodone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine PO

              oxycodone increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • phenytoin

              phenytoin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pholcodine

              oxycodone and pholcodine both increase sedation. Use Caution/Monitor.

            • pimozide

              oxycodone and pimozide both increase sedation. Use Caution/Monitor.

            • pirbuterol

              oxycodone increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pregabalin

              pregabalin, oxycodone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

              primidone and oxycodone both increase sedation. Use Caution/Monitor.

              primidone decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • prochlorperazine

              oxycodone and prochlorperazine both increase sedation. Use Caution/Monitor.

            • promethazine

              promethazine and oxycodone both increase sedation. Use Caution/Monitor.

            • propafenone

              propafenone will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • propofol

              propofol and oxycodone both increase sedation. Use Caution/Monitor.

            • propylhexedrine

              oxycodone increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protriptyline

              oxycodone and protriptyline both increase sedation. Use Caution/Monitor.

            • quazepam

              quazepam and oxycodone both increase sedation. Use Caution/Monitor.

            • quetiapine

              oxycodone and quetiapine both increase sedation. Use Caution/Monitor.

            • quinacrine

              quinacrine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • quinidine

              quinidine decreases effects of oxycodone by decreasing metabolism. Use Caution/Monitor. Decreased conversion of hydrocodone to active metabolite morphine.

            • ramelteon

              oxycodone and ramelteon both increase sedation. Use Caution/Monitor.

            • ranolazine

              ranolazine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • remimazolam

              remimazolam, oxycodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • ribociclib

              ribociclib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              rifabutin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifampin

              rifampin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifapentine

              rifapentine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • risperidone

              oxycodone and risperidone both increase sedation. Use Caution/Monitor.

            • rocuronium

              oxycodone increases effects of rocuronium by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Oxycodone may enhance the neuromuscular blocking action of true skeletal muscle relaxants and produce an increased degree of respiratory depression.

            • rucaparib

              rucaparib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • salmeterol

              oxycodone increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • scullcap

              oxycodone and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital and oxycodone both increase sedation. Use Caution/Monitor.

            • selegiline

              selegiline increases toxicity of oxycodone by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.

            • sertraline

              sertraline will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2B6 metabolism. Use Caution/Monitor.

              oxycodone increases effects of sertraline by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Opioids may enhance the serotonergic effects of SSRIs and increase risk for serotonergic syndrome.

            • sevoflurane

              sevoflurane and oxycodone both increase sedation. Use Caution/Monitor.

            • shepherd's purse

              oxycodone and shepherd's purse both increase sedation. Use Caution/Monitor.

            • St John's Wort

              St John's Wort decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • stiripentol

              stiripentol, oxycodone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol, oxycodone. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • succinylcholine

              oxycodone increases effects of succinylcholine by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Oxycodone may enhance the neuromuscular blocking action of true skeletal muscle relaxants and produce an increased degree of respiratory depression.

            • sufentanil

              oxycodone and sufentanil both increase sedation. Use Caution/Monitor.

            • tapentadol

              oxycodone and tapentadol both increase sedation. Use Caution/Monitor.

            • tazemetostat

              acetaminophen will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              tazemetostat will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • tetracaine

              tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

            • temazepam

              temazepam and oxycodone both increase sedation. Use Caution/Monitor.

            • terbutaline

              oxycodone increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • thioridazine

              thioridazine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              oxycodone and thioridazine both increase sedation. Use Caution/Monitor.

            • thiothixene

              oxycodone and thiothixene both increase sedation. Use Caution/Monitor.

            • tinidazole

              acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tipranavir

              tipranavir will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • topiramate

              oxycodone and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • tramadol

              oxycodone and tramadol both increase sedation. Use Caution/Monitor.

            • trazodone

              oxycodone and trazodone both increase sedation. Use Caution/Monitor.

            • triazolam

              triazolam and oxycodone both increase sedation. Use Caution/Monitor.

            • triclofos

              triclofos and oxycodone both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              oxycodone and trifluoperazine both increase sedation. Use Caution/Monitor.

            • trimipramine

              oxycodone and trimipramine both increase sedation. Use Caution/Monitor.

            • triprolidine

              triprolidine and oxycodone both increase sedation. Use Caution/Monitor.

            • vecuronium

              oxycodone increases effects of vecuronium by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Oxycodone may enhance the neuromuscular blocking action of true skeletal muscle relaxants and produce an increased degree of respiratory depression.

            • venlafaxine

              venlafaxine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • vilazodone

              oxycodone increases effects of vilazodone by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Opioids may enhance the serotonergic effects of SSRIs and increase risk for serotonergic syndrome.

            • warfarin

              acetaminophen increases effects of warfarin by unknown mechanism. Use Caution/Monitor.

            • xylometazoline

              oxycodone increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            Minor (68)

            • acetazolamide

              acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • albiglutide

              albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

            • amiodarone

              amiodarone decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • antithrombin alfa

              acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.

            • antithrombin III

              acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.

            • argatroban

              acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.

            • bemiparin

              acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.

            • bivalirudin

              acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.

            • brimonidine

              brimonidine increases effects of oxycodone by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • carbamazepine

              carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • celecoxib

              celecoxib decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • chloroquine

              chloroquine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • cholestyramine

              cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • clonazepam

              clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • colestipol

              colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • dalteparin

              acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.

            • dextroamphetamine

              dextroamphetamine increases effects of oxycodone by unspecified interaction mechanism. Minor/Significance Unknown.

            • diazepam

              diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • diphenhydramine

              diphenhydramine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • disulfiram

              disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • enoxaparin

              acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.

            • ethanol

              ethanol will decrease the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

              ethanol increases toxicity of acetaminophen by decreasing metabolism. Minor/Significance Unknown.

            • ethosuximide

              ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • eucalyptus

              oxycodone and eucalyptus both increase sedation. Minor/Significance Unknown.

            • felbamate

              felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • fondaparinux

              acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.

            • fosphenytoin

              fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • gabapentin

              gabapentin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • gabapentin enacarbil

              gabapentin enacarbil decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • green tea

              green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

            • haloperidol

              haloperidol decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • heparin

              acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.

            • imatinib

              imatinib decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • isoniazid

              isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

            • lacosamide

              lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • lamotrigine

              lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • levetiracetam

              levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • lidocaine

              lidocaine increases toxicity of oxycodone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

            • liraglutide

              liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

            • lorazepam

              lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • methsuximide

              methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • metoclopramide

              metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • metronidazole

              metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • oxcarbazepine

              oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • oxybutynin

              oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

            • oxybutynin topical

              oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

            • oxybutynin transdermal

              oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

            • paroxetine

              paroxetine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • perphenazine

              perphenazine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • phenindione

              acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.

            • phenobarbital

              phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • phenytoin

              phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • primidone

              primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • propafenone

              propafenone decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • protamine

              acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.

            • quinacrine

              quinacrine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • rifabutin

              rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • rifampin

              rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • rufinamide

              rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • ruxolitinib

              acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sage

              oxycodone and sage both increase sedation. Minor/Significance Unknown.

            • thioridazine

              thioridazine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • tiagabine

              tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • topiramate

              topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • valproic acid

              valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

            • venlafaxine

              venlafaxine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • ziconotide

              ziconotide, oxycodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

            • zonisamide

              zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.

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            Adverse Effects

            Frequency Not Defined

            Lightheadedness

            Dizziness

            Drowsiness or sedation

            Nausea and vomiting

            Euphoria

            Dysphoria

            Constipation

            Pruritus

            Skin and urticarial eruptions

            Fatal hepatic necrosis (rare; associated with high/chronic acetaminophen use)

            Renal tubular necrosis

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            Warnings

            Black Box Warnings

            Oxycodone

            • Risk of addiction, abuse, and misuse, which can lead to overdose and death; assess patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions
            • Serious, life-threatening, or fatal respiratory depression may occur
            • Accidental consumption, especially in children, can result in fatal overdose
            • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated

            Acetaminophen

            • Hepatotoxicity may occur with acetaminophen doses that exceed 4 g/day; take into account all acetaminophen-containing products the patient is taking, including PRN doses and OTC products
            • Acetaminophen associated with cases of acute liver failure, at times resulting in liver transplantation or death
            • New dosage limit allows no more than 325 mg/dosage unit for prescription medications that contain acetaminophen
            • Healthcare professionals can direct patients to take 1 or 2 tablets, capsules, or other dosage units of a prescription product containing 325 mg of acetaminophen up to 6 times a day (12 dosage units) and still not exceed the maximum daily dose of acetaminophen of 4 g/day

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • Healthcare providers are strongly 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
              • Consider other tools to improve patient, household, and community safety

            Interaction with central nervous system (CNS) depressants

            • Coadministration with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
            • Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation
            • Instruct patients not to consume alcoholic beverages or use alcohol-containing drug products while taking morphine due to risk of additive sedation and respiratory depression

            Contraindications

            Hypersensitivity

            Suspected or known gastrointestinal obstruction, including paralytic ileus

            Acute or severe bronchial asthma or hypercarbia

            Significant respiratory depression (bronchial asthma, hypercarbia, COPD)

            Cautions

            Therapy may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock

            In patients who may be susceptible to intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma

            Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; may cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

            Therapy may increase frequency of seizures in patients with seizure disorders and in other clinical settings associated with seizures; monitor patients for worsened seizure control during therapy

            Warn patients not to drive or operate dangerous machinery unless they are tolerant to effects of drug and know how they will react to medication

            While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, risk is greatest during initiation of therapy or following dosage increase; monitor patients closely for respiratory depression, especially within first 24-72 hr of initiating therapy with and following dosage increases; accidental ingestion of even one dose, especially by children, can result in respiratory depression and death due to overdose of opioid

            Deaths have occurred in nursing infants exposed to high levels of opioid in breast milk because mothers were ultra-rapid metabolizers of opioid

            Use in patients with acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment is contraindicated; patients with significant chronic obstructive pulmonary disease or cor pulmonale, and with substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages

            Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients; monitor closely

            Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency

            Use caution when selecting dosage for an elderly patient, usually starting at low end of dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy; because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and may be useful to monitor renal function

            Opioid pharmacokinetics may be altered in patients with renal failure; clearance may be decreased and metabolites may accumulate much higher plasma levels in patients with renal failure as compared to patients with normal renal function; start with a lower than normal dosage or with longer dosing intervals and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension

            Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; if an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response; follow patients closely for signs and symptoms of respiratory depression and sedation; if concomitant use with benzodiazepine or muscle relaxant warranted, consider prescribing naloxone for the emergency treatment of opioid overdose

            Due to risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose

            Extended release formulation is not interchangeable with other oxycodone/acetaminophen products due to differing pharmacokinetic parameters

            Use caution in hypothyroidism and Addison disease

            Acetaminophen associated with cases of acute liver failure, at times resulting in liver transplantation or death; risk increases in individuals with underlying liver disease, alcohol ingestion, and/or use of more than 1 acetaminophen-containing product (see Black Box Warnings)

            Acetaminophen: Risk for rare, but serious skin reactions that can be fatal; these reactions include Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP); symptoms may include skin redness, blisters and rash

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products
            • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
            • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
            • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
            • To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint

            Patient access to naloxone for emergency treatment of opioid overdose

            • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
            • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
            • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose

            Drug interaction overview

            • Monoamine oxidase inhibitors (MAOIs) may potentiate effects of opioid, opioid’s active metabolite, including respiratory depression, coma, and confusion; therapy should not be administered within 14 days of initiating or stopping MAOIs
            • Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (eg, nonbenzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate
            • Avoid use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; mixed agonist/antagonist and partial agonist analgesics may reduce analgesic effect and/or precipitate withdrawal symptoms; when discontinuing therapy in physically-dependent patient, gradually taper dosage; do not abruptly discontinue therapy in these patients
            • Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected
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            Pregnancy & Lactation

            Pregnancy

            Prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome; there are no available data in pregnant women to inform a drug associated risk for major birth defects and miscarriage; published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects

            Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

            Severe fetal bradycardia reported when administered during labor; naloxone may reverse these effects; although there are no reports of fetal bradycardia earlier in pregnancy, it is possible it may occur; drug should be used in pregnancy only if clearly needed, if potential benefit outweighs risk to fetus, and if appropriate measures such as fetal monitoring are taken to detect and manage potential adverse effect on fetus

            Labor or delivery

            • Opioids cross placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in neonate; drug is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that temporarily reduce strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression

            Infertility

            • Due to effects of androgen deficiency, chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible

            Lactation

            Drug is present in breast milk; published lactation studies report variable concentrations of drug in breast milk with administration of immediate-release formulation to nursing mothers in early postpartum period

            The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

            Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding is stopped

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Oxycodone: Opioid agonist that is relatively selective for mu and kappa opioid receptors; inhibits ascending pain pathways, which causes alteration in response to pain; produces analgesia, respiratory depression, and sedation

            Acetaminophen: Nonopioid, nonsalicylate analgesic; may work peripherally to block pain impulse generation; acts on hypothalamus to produce antipyresis

            Absorption

            Bioavailability: Oxycodone (87%); acetaminophen (100%)

            Onset: Oxycodone (10-15 min)

            Duration: Oxycodone (3-6 hr)

            Peak plasma time: Oxycodone (0.5-1 hr)

            Distribution

            Protein bound: Acetaminophen (20-50%); oxycodone (45%)

            Vd: 2.6 L/kg (oxycodone)

            Metabolism

            Oxycodone

            • Metabolized via hepatic P450 enzyme CYP2D6 and CYP3A4
            • Active prodrug metabolized to oxymorphone (active metabolite) via CYP2D6
            • CYP2D6 poor metabolizers may not achieve adequate analgesia because of decreased conversion to active metabolite
            • Ultrarapid metabolizers (up to 7% of whites and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion

            Acetaminophen

            • Metabolized in liver by microsomal enzyme systems
            • 80-85% conjugated, principally with glucuronic acid and to a lesser extent with sulfuric acid and cysteine
            • 4% metabolized by CYP450 to toxic metabolite (N acetyl-p-benzoquinoneimine, N-acetylimidoquinone [NAPQI]), which is detoxified by conjugation with glutathione; high doses may deplete fixed amount of glutathione in body, causing NAPQI accumulation

            Elimination

            Oxycodone

            • Half-life: 3.5 hr
            • Excretion: Primarily in urine (8-14% as free oxycodone)

            Acetaminophen

            • Half-life: 2-4 hr
            • Excretion: 90-100% in urine (principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate)
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            Administration

            Oral Administration

            Extended-release tablet: Swallow whole with enough water to ensure complete swallowing after placing in mouth; do not break, chew, cut, crush, dissolve or split the tablets

            Discontinuation: Opioid tolerance may occur; gradually taper dose when discontinuing if patient treated for more than a few weeks

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.