oxycodone/acetaminophen (Rx)

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)

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)

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 (65)

• acrivastine

  acrivastine and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• amisulpride

  amisulpride and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• asenapine

  asenapine and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• asenapine transdermal

  asenapine transdermal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• avapritinib

  avapritinib and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.
  
  benzhydrocodone/acetaminophen and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• brexpiprazole

  brexpiprazole and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brimonidine

  brimonidine and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brivaracetam

  brivaracetam and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  buprenorphine transdermal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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 and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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 intranasal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl iontophoretic transdermal system

  fentanyl iontophoretic transdermal system and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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 transdermal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• fexinidazole

  fexinidazole will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• 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.

• larotrectinib

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

• 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.

• olopatadine intranasal

  oxycodone and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• 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 (283)

• 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.

• atogepant

  acetaminophen will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 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.

• ceritinib

  ceritinib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 .

• daridorexant

  oxycodone and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• 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.

• difelikefalin

  difelikefalin and oxycodone both increase sedation. 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.

• ganaxolone

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

• 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.

• isavuconazonium sulfate

  acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

• ketoconazole

  ketoconazole 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.

• 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.

• lenacapavir

  lenacapavir will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Careful monitoring of therapeutic effects

• 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.

• letermovir

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

• levalbuterol

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

• levoketoconazole

  levoketoconazole 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.

• 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 (DSC)

  lixisenatide (DSC) 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.

• nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Careful monitoring of oxycodone therapeutic and adverse effects (including potentially fatal respiratory depression) recommended when coadministered. Reduce oxycodone dose if necessary.

• 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 anticoagulation. Use Caution/Monitor.

• xylometazoline

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

Minor (69)

• acetazolamide

  acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  acetazolamide will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• 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.

• anastrozole

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

• 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.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

• 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.

• ruxolitinib topical

  acetaminophen will increase the level or effect of ruxolitinib topical 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.

• acetazolamide

  Minor (2)acetazolamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.
  
  acetazolamide will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acrivastine

  Serious - Use Alternative (1)acrivastine and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• albiglutide

  Minor (1)albiglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• albuterol

  Monitor Closely (1)oxycodone increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfentanil

  Monitor Closely (1)alfentanil and oxycodone both increase sedation. Use Caution/Monitor.

• alprazolam

  Monitor Closely (1)alprazolam and oxycodone both increase sedation. Use Caution/Monitor.

• alvimopan

  Contraindicated (1)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.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)amiodarone decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• amisulpride

  Serious - Use Alternative (1)amisulpride and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• amitriptyline

  Monitor Closely (1)oxycodone and amitriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

  Monitor Closely (1)amobarbital and oxycodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amobarbital will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• amoxapine

  Monitor Closely (1)oxycodone and amoxapine both increase sedation. Use Caution/Monitor.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• antithrombin alfa

  Minor (1)acetaminophen increases effects of antithrombin alfa by unknown mechanism. Minor/Significance Unknown.

• antithrombin III

  Minor (1)acetaminophen increases effects of antithrombin III by unknown mechanism. Minor/Significance Unknown.

• apalutamide

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• apomorphine

  Monitor Closely (1)oxycodone and apomorphine both increase sedation. Use Caution/Monitor.

• arformoterol

  Monitor Closely (1)oxycodone increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• argatroban

  Minor (1)acetaminophen increases effects of argatroban by unknown mechanism. Minor/Significance Unknown.

• aripiprazole

  Monitor Closely (1)oxycodone and aripiprazole both increase sedation. Use Caution/Monitor.

• armodafinil

  Monitor Closely (1)oxycodone increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• artemether/lumefantrine

  Serious - Use Alternative (1)artemether/lumefantrine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• asenapine

  Monitor Closely (1)asenapine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• asenapine transdermal

  Serious - Use Alternative (1)asenapine transdermal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• atazanavir

  Serious - Use Alternative (1)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.

• atogepant

  Monitor Closely (1)acetaminophen will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atracurium

  Monitor Closely (1)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

  Monitor Closely (1)acetaminophen will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)avapritinib and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• axitinib

  Monitor Closely (1)acetaminophen increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• azelastine

  Monitor Closely (1)azelastine and oxycodone both increase sedation. Use Caution/Monitor.

• baclofen

  Monitor Closely (1)baclofen and oxycodone both increase sedation. Use Caution/Monitor.

• belladonna and opium

  Monitor Closely (1)belladonna and opium and oxycodone both increase sedation. Use Caution/Monitor.

• bemiparin

  Minor (1)acetaminophen increases effects of bemiparin by unknown mechanism. Minor/Significance Unknown.

• benperidol

  Monitor Closely (1)oxycodone and benperidol both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (2)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.
  
  benzhydrocodone/acetaminophen and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzphetamine

  Monitor Closely (1)oxycodone increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• bivalirudin

  Minor (1)acetaminophen increases effects of bivalirudin by unknown mechanism. Minor/Significance Unknown.

• bosentan

  Monitor Closely (1)bosentan decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bremelanotide

  Serious - Use Alternative (1)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.

• brexanolone

  Monitor Closely (1)brexanolone, oxycodone. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Serious - Use Alternative (1)brexpiprazole and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brimonidine

  Serious - Use Alternative (1)brimonidine and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequateMinor (1)brimonidine increases effects of oxycodone by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brivaracetam

  Serious - Use Alternative (1)brivaracetam and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brompheniramine

  Monitor Closely (1)brompheniramine and oxycodone both increase sedation. Use Caution/Monitor.

• bupivacaine implant

  Monitor Closely (1)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

  Monitor Closely (1)buprenorphine and oxycodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (1)buprenorphine buccal and oxycodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)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.

• buprenorphine subdermal implant

  Serious - Use Alternative (1)buprenorphine subdermal implant and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  Serious - Use Alternative (1)buprenorphine transdermal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (1)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.Serious - Use Alternative (1)buprenorphine, long-acting injection and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bupropion

  Monitor Closely (1)bupropion will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• busulfan

  Monitor Closely (1)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

  Monitor Closely (1)butabarbital and oxycodone both increase sedation. Use Caution/Monitor.

• butalbital

  Monitor Closely (1)butalbital and oxycodone both increase sedation. Use Caution/Monitor.

• butorphanol

  Monitor Closely (1)butorphanol and oxycodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)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.

• caffeine

  Monitor Closely (1)oxycodone increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)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.

• carbamazepine

  Monitor Closely (1)carbamazepine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)carbamazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• carbinoxamine

  Monitor Closely (1)carbinoxamine and oxycodone both increase sedation. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (1)carisoprodol and oxycodone both increase sedation. Use Caution/Monitor.

• celecoxib

  Monitor Closely (1)celecoxib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)celecoxib decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• cenobamate

  Monitor Closely (2)cenobamate, oxycodone. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  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.

• ceritinib

  Monitor Closely (1)ceritinib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chloral hydrate

  Monitor Closely (1)chloral hydrate and oxycodone both increase sedation. Use Caution/Monitor.

• chloramphenicol

  Monitor Closely (1)chloramphenicol will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (1)chlordiazepoxide and oxycodone both increase sedation. Use Caution/Monitor.

• chloroquine

  Monitor Closely (1)chloroquine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)chloroquine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• chlorpheniramine

  Monitor Closely (1)chlorpheniramine and oxycodone both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (1)oxycodone and chlorpromazine both increase sedation. Use Caution/Monitor.

• chlorzoxazone

  Monitor Closely (1)chlorzoxazone and oxycodone both increase sedation. Use Caution/Monitor.

• cholestyramine

  Minor (1)cholestyramine decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cimetidine

  Monitor Closely (1)cimetidine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)cimetidine increases effects of oxycodone by decreasing metabolism. Avoid or Use Alternate Drug.

• cinnarizine

  Monitor Closely (1)cinnarizine and oxycodone both increase sedation. Use Caution/Monitor.

• cisatracurium

  Monitor Closely (1)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

  Monitor Closely (1)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.

• clarithromycin

  Serious - Use Alternative (1)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.

• clemastine

  Monitor Closely (1)clemastine and oxycodone both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (1)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

  Monitor Closely (1)oxycodone and clomipramine both increase sedation. Use Caution/Monitor.

• clonazepam

  Monitor Closely (1)clonazepam and oxycodone both increase sedation. Use Caution/Monitor.Minor (1)clonazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• clonidine

  Serious - Use Alternative (1)clonidine, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• clorazepate

  Monitor Closely (1)clorazepate and oxycodone both increase sedation. Use Caution/Monitor.

• clozapine

  Monitor Closely (1)oxycodone and clozapine both increase sedation. Use Caution/Monitor.

• cobicistat

  Monitor Closely (1)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

  Monitor Closely (1)codeine and oxycodone both increase sedation. Use Caution/Monitor.

• colestipol

  Minor (1)colestipol decreases levels of acetaminophen by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• conivaptan

  Serious - Use Alternative (1)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.

• crizotinib

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)cyclizine and oxycodone both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (1)cyclobenzaprine and oxycodone both increase sedation. Use Caution/Monitor.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyproheptadine

  Monitor Closely (1)cyproheptadine and oxycodone both increase sedation. Use Caution/Monitor.

• dabrafenib

  Monitor Closely (1)dabrafenib decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dalteparin

  Minor (1)acetaminophen increases effects of dalteparin by unknown mechanism. Minor/Significance Unknown.

• dantrolene

  Monitor Closely (1)dantrolene and oxycodone both increase sedation. Use Caution/Monitor.

• dapsone topical

  Monitor Closely (1)acetaminophen increases toxicity of dapsone topical by altering metabolism. Modify Therapy/Monitor Closely. May induce methemoglobinemia .

• daridorexant

  Monitor Closely (1)oxycodone and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

  Monitor Closely (1)darifenacin will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• darunavir

  Monitor Closely (1)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

  Monitor Closely (1)desflurane and oxycodone both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

• desipramine

  Monitor Closely (1)oxycodone and desipramine both increase sedation. Use Caution/Monitor.

• desvenlafaxine

  Monitor Closely (1)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

  Monitor Closely (1)oxycodone and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexamethasone

  Monitor Closely (1)dexamethasone decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (1)dexchlorpheniramine and oxycodone both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (1)oxycodone increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmedetomidine

  Monitor Closely (1)dexmedetomidine and oxycodone both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (1)oxycodone increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (1)oxycodone increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)dextroamphetamine increases effects of oxycodone by unspecified interaction mechanism. Minor/Significance Unknown.

• dextromoramide

  Monitor Closely (1)dextromoramide and oxycodone both increase sedation. Use Caution/Monitor.

• diamorphine

  Monitor Closely (1)diamorphine and oxycodone both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (1)diazepam and oxycodone both increase sedation. Use Caution/Monitor.Minor (1)diazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• diazepam intranasal

  Serious - Use Alternative (1)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.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

• diethylpropion

  Monitor Closely (1)oxycodone increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  Monitor Closely (1)difelikefalin and oxycodone both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (1)difenoxin hcl and oxycodone both increase sedation. Use Caution/Monitor.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dimenhydrinate

  Monitor Closely (1)dimenhydrinate and oxycodone both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (2)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.Minor (1)diphenhydramine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• diphenoxylate hcl

  Monitor Closely (1)diphenoxylate hcl and oxycodone both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (1)dipipanone and oxycodone both increase sedation. Use Caution/Monitor.

• disulfiram

  Minor (1)disulfiram will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• dobutamine

  Monitor Closely (1)oxycodone increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopamine

  Monitor Closely (1)oxycodone increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopexamine

  Monitor Closely (1)oxycodone increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  Monitor Closely (1)oxycodone and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  Monitor Closely (1)oxycodone and doxepin both increase sedation. Use Caution/Monitor.

• doxylamine

  Monitor Closely (1)doxylamine and oxycodone both increase sedation. Use Caution/Monitor.

• dronedarone

  Monitor Closely (1)dronedarone will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• droperidol

  Monitor Closely (1)oxycodone and droperidol both increase sedation. Use Caution/Monitor.

• duloxetine

  Monitor Closely (1)duloxetine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• duvelisib

  Monitor Closely (1)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

  Monitor Closely (1)efavirenz decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elagolix

  Monitor Closely (1)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

  Monitor Closely (2)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.

• eluxadoline

  Serious - Use Alternative (1)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. .

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)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.

• encorafenib

  Monitor Closely (1)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.

• enoxaparin

  Minor (1)acetaminophen increases effects of enoxaparin by unknown mechanism. Minor/Significance Unknown.

• enzalutamide

  Monitor Closely (1)enzalutamide decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ephedrine

  Monitor Closely (1)oxycodone increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  Monitor Closely (1)oxycodone increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (1)oxycodone increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• escitalopram

  Monitor Closely (1)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

  Monitor Closely (1)esketamine intranasal, oxycodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estazolam

  Monitor Closely (1)estazolam and oxycodone both increase sedation. Use Caution/Monitor.

• eszopiclone

  Serious - Use Alternative (1)eszopiclone and oxycodone both increase sedation. Avoid or Use Alternate Drug. Additive CNS depression may lead to hypotension, profound sedation, respiratory depression, or coma

• ethanol

  Monitor Closely (1)oxycodone and ethanol both increase sedation. Use Caution/Monitor.Minor (2)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

  Minor (1)ethosuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• etomidate

  Monitor Closely (1)etomidate and oxycodone both increase sedation. Use Caution/Monitor.

• etravirine

  Monitor Closely (1)etravirine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eucalyptus

  Minor (1)oxycodone and eucalyptus both increase sedation. Minor/Significance Unknown.

• exenatide injectable solution

  Monitor Closely (1)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.

• exenatide injectable suspension

  Monitor Closely (1)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

  Monitor Closely (1)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.

• felbamate

  Minor (1)felbamate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• fenfluramine

  Monitor Closely (1)oxycodone increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fentanyl

  Serious - Use Alternative (2)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 and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl intranasal

  Serious - Use Alternative (2)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 intranasal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl iontophoretic transdermal system

  Serious - Use Alternative (1)fentanyl iontophoretic transdermal system and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transdermal

  Serious - Use Alternative (2)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 transdermal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transmucosal

  Serious - Use Alternative (1)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.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• finerenone

  Monitor Closely (1)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

  Monitor Closely (2)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.

• fluoxetine

  Serious - Use Alternative (1)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

• fluphenazine

  Monitor Closely (1)oxycodone and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  Monitor Closely (1)flurazepam and oxycodone both increase sedation. Use Caution/Monitor.

• fluvoxamine

  Monitor Closely (1)fluvoxamine and oxycodone both increase serotonin levels. Use Caution/Monitor.

• fondaparinux

  Minor (1)acetaminophen increases effects of fondaparinux by unknown mechanism. Minor/Significance Unknown.

• formoterol

  Monitor Closely (1)oxycodone increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fosamprenavir

  Serious - Use Alternative (1)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 .

• fosphenytoin

  Monitor Closely (1)fosphenytoin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)fosphenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• gabapentin

  Monitor Closely (1)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

  Monitor Closely (1)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.

• ganaxolone

  Monitor Closely (1)oxycodone and ganaxolone both increase sedation. Use Caution/Monitor.

• grapefruit

  Serious - Use Alternative (1)grapefruit will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• green tea

  Minor (1)green tea increases effects of acetaminophen by pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical, due to caffeine content).

• haloperidol

  Monitor Closely (2)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.Minor (1)haloperidol decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• heparin

  Minor (1)acetaminophen increases effects of heparin by unknown mechanism. Minor/Significance Unknown.

• hydrocodone

  Serious - Use Alternative (1)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.

• hydromorphone

  Monitor Closely (1)hydromorphone and oxycodone both increase sedation. Use Caution/Monitor.

• hydroxyzine

  Monitor Closely (1)hydroxyzine and oxycodone both increase sedation. Use Caution/Monitor.

• idelalisib

  Serious - Use Alternative (1)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

• iloperidone

  Monitor Closely (2)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.
  
  oxycodone and iloperidone both increase sedation. Use Caution/Monitor.

• imatinib

  Monitor Closely (2)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.
  
  imatinib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)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.Minor (1)imatinib decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• imipramine

  Monitor Closely (1)oxycodone and imipramine both increase sedation. Use Caution/Monitor.

• indinavir

  Serious - Use Alternative (1)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.

• isavuconazonium sulfate

  Monitor Closely (1)acetaminophen will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isocarboxazid

  Serious - Use Alternative (1)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

  Monitor Closely (1)isoniazid will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)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.Minor (1)isoniazid increases toxicity of acetaminophen by unknown mechanism. Minor/Significance Unknown.

• isoproterenol

  Monitor Closely (1)oxycodone increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• istradefylline

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)acetaminophen increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

• ivosidenib

  Serious - Use Alternative (1)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.

• ketamine

  Monitor Closely (1)ketamine and oxycodone both increase sedation. Use Caution/Monitor.

• ketoconazole

  Monitor Closely (1)ketoconazole 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.

• ketotifen, ophthalmic

  Monitor Closely (1)oxycodone and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• lacosamide

  Minor (1)lacosamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lamotrigine

  Minor (1)lamotrigine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• larotrectinib

  Serious - Use Alternative (1)larotrectinib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lasmiditan

  Monitor Closely (1)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

  Monitor Closely (2)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.

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Careful monitoring of therapeutic effects

• letermovir

  Monitor Closely (1)letermovir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (1)oxycodone increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levetiracetam

  Minor (1)levetiracetam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• levoketoconazole

  Monitor Closely (1)levoketoconazole 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.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (2)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.

• levorphanol

  Monitor Closely (1)levorphanol and oxycodone both increase sedation. Use Caution/Monitor.

• lidocaine

  Minor (1)lidocaine increases toxicity of oxycodone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

• linezolid

  Serious - Use Alternative (1)linezolid increases toxicity of oxycodone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• liraglutide

  Minor (1)liraglutide decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• lisdexamfetamine

  Monitor Closely (1)oxycodone increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lixisenatide (DSC)

  Monitor Closely (1)lixisenatide (DSC) 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

  Monitor Closely (1)oxycodone and lofepramine both increase sedation. Use Caution/Monitor.

• lofexidine

  Monitor Closely (1)oxycodone and lofexidine both increase sedation. Use Caution/Monitor.

• lomitapide

  Monitor Closely (1)acetaminophen increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

• lonafarnib

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• loprazolam

  Monitor Closely (1)loprazolam and oxycodone both increase sedation. Use Caution/Monitor.

• lorazepam

  Monitor Closely (1)lorazepam and oxycodone both increase sedation. Use Caution/Monitor.Minor (1)lorazepam decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• lorlatinib

  Monitor Closely (1)lorlatinib will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lormetazepam

  Monitor Closely (1)lormetazepam and oxycodone both increase sedation. Use Caution/Monitor.

• loxapine

  Monitor Closely (1)oxycodone and loxapine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (1)oxycodone and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lumefantrine

  Serious - Use Alternative (1)lumefantrine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• lurasidone

  Monitor Closely (1)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

  Monitor Closely (1)oxycodone and maprotiline both increase sedation. Use Caution/Monitor.

• maraviroc

  Monitor Closely (1)maraviroc will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• marijuana

  Monitor Closely (2)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

  Monitor Closely (1)oxycodone and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (1)meperidine and oxycodone both increase sedation. Use Caution/Monitor.

• meprobamate

  Monitor Closely (1)oxycodone and meprobamate both increase sedation. Use Caution/Monitor.

• metaproterenol

  Monitor Closely (1)oxycodone increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  Monitor Closely (1)metaxalone and oxycodone both increase sedation. Use Caution/Monitor.

• methadone

  Monitor Closely (1)methadone and oxycodone both increase sedation. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (1)oxycodone increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methocarbamol

  Monitor Closely (1)methocarbamol and oxycodone both increase sedation. Use Caution/Monitor.

• methsuximide

  Minor (1)methsuximide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• methylene blue

  Serious - Use Alternative (1)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

• methylenedioxymethamphetamine

  Monitor Closely (1)oxycodone increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metoclopramide

  Minor (1)metoclopramide increases levels of acetaminophen by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• metoclopramide intranasal

  Serious - Use Alternative (1)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.

• metronidazole

  Minor (1)metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

• midazolam

  Monitor Closely (1)midazolam and oxycodone both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (2)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

  Monitor Closely (1)oxycodone increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mifepristone

  Monitor Closely (1)mifepristone will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mipomersen

  Monitor Closely (1)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.

• mirtazapine

  Monitor Closely (1)oxycodone and mirtazapine both increase sedation. Use Caution/Monitor.

• mitotane

  Monitor Closely (1)mitotane decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• modafinil

  Monitor Closely (1)oxycodone increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• morphine

  Monitor Closely (1)morphine and oxycodone both increase sedation. Use Caution/Monitor.

• motherwort

  Monitor Closely (1)oxycodone and motherwort both increase sedation. Use Caution/Monitor.

• moxonidine

  Monitor Closely (1)oxycodone and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (1)oxycodone and nabilone both increase sedation. Use Caution/Monitor.

• nafcillin

  Monitor Closely (1)nafcillin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (1)nalbuphine and oxycodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• nevirapine

  Monitor Closely (1)nevirapine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nicardipine

  Serious - Use Alternative (1)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.

• nilotinib

  Monitor Closely (1)nilotinib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• nirmatrelvir/ritonavir

  Monitor Closely (1)nirmatrelvir/ritonavir will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Careful monitoring of oxycodone therapeutic and adverse effects (including potentially fatal respiratory depression) recommended when coadministered. Reduce oxycodone dose if necessary.

• norepinephrine

  Monitor Closely (1)oxycodone increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nortriptyline

  Monitor Closely (1)oxycodone and nortriptyline both increase sedation. Use Caution/Monitor.

• olanzapine

  Monitor Closely (1)oxycodone and olanzapine both increase sedation. Use Caution/Monitor.

• oliceridine

  Monitor Closely (1)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.

• olopatadine intranasal

  Serious - Use Alternative (1)oxycodone and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• opium tincture

  Monitor Closely (1)opium tincture and oxycodone both increase sedation. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (1)orphenadrine and oxycodone both increase sedation. Use Caution/Monitor.

• oxazepam

  Monitor Closely (1)oxazepam and oxycodone both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  Monitor Closely (1)oxcarbazepine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)oxcarbazepine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• oxybutynin

  Minor (1)oxybutynin decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  Minor (1)oxybutynin topical decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  Minor (1)oxybutynin transdermal decreases levels of acetaminophen by unspecified interaction mechanism. Minor/Significance Unknown.

• oxymorphone

  Monitor Closely (1)oxycodone and oxymorphone both increase sedation. Use Caution/Monitor.

• ozanimod

  Serious - Use Alternative (1)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.

• paliperidone

  Monitor Closely (1)oxycodone and paliperidone both increase sedation. Use Caution/Monitor.

• pancuronium

  Monitor Closely (1)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

  Monitor Closely (1)oxycodone and papaveretum both increase sedation. Use Caution/Monitor.

• papaverine

  Monitor Closely (1)oxycodone and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Monitor Closely (1)parecoxib will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• paroxetine

  Monitor Closely (1)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.Serious - Use Alternative (1)paroxetine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.Minor (1)paroxetine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• pegvisomant

  Monitor Closely (1)oxycodone decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

• pentazocine

  Monitor Closely (1)oxycodone and pentazocine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)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.

• pentobarbital

  Monitor Closely (2)pentobarbital decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  pentobarbital and oxycodone both increase sedation. Use Caution/Monitor.

• perampanel

  Monitor Closely (1)perampanel and oxycodone both decrease sedation. Use Caution/Monitor.

• perphenazine

  Monitor Closely (2)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.Minor (1)perphenazine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• pexidartinib

  Serious - Use Alternative (1)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.

• phendimetrazine

  Monitor Closely (1)oxycodone increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenelzine

  Serious - Use Alternative (1)phenelzine increases toxicity of oxycodone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• phenindione

  Minor (1)acetaminophen increases effects of phenindione by unknown mechanism. Minor/Significance Unknown.

• phenobarbital

  Monitor Closely (2)phenobarbital decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  phenobarbital and oxycodone both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• phentermine

  Monitor Closely (1)oxycodone increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine

  Monitor Closely (1)oxycodone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine PO

  Monitor Closely (1)oxycodone increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• phenytoin

  Monitor Closely (1)phenytoin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)phenytoin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• pholcodine

  Monitor Closely (1)oxycodone and pholcodine both increase sedation. Use Caution/Monitor.

• pimozide

  Monitor Closely (1)oxycodone and pimozide both increase sedation. Use Caution/Monitor.

• pirbuterol

  Monitor Closely (1)oxycodone increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• posaconazole

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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

• pregabalin

  Monitor Closely (1)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.

• pretomanid

  Serious - Use Alternative (1)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.

• primidone

  Monitor Closely (2)primidone decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  primidone and oxycodone both increase sedation. Use Caution/Monitor.Minor (1)primidone decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• procarbazine

  Serious - Use Alternative (1)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. .

• prochlorperazine

  Monitor Closely (1)oxycodone and prochlorperazine both increase sedation. Use Caution/Monitor.

• promethazine

  Monitor Closely (1)promethazine and oxycodone both increase sedation. Use Caution/Monitor.

• propafenone

  Monitor Closely (1)propafenone will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)propafenone decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• propofol

  Monitor Closely (1)propofol and oxycodone both increase sedation. Use Caution/Monitor.

• propylhexedrine

  Monitor Closely (1)oxycodone increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protamine

  Minor (1)acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.

• protriptyline

  Monitor Closely (1)oxycodone and protriptyline both increase sedation. Use Caution/Monitor.

• quazepam

  Monitor Closely (1)quazepam and oxycodone both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (1)oxycodone and quetiapine both increase sedation. Use Caution/Monitor.

• quinacrine

  Monitor Closely (1)quinacrine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)quinacrine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• quinidine

  Monitor Closely (1)quinidine decreases effects of oxycodone by decreasing metabolism. Use Caution/Monitor. Decreased conversion of hydrocodone to active metabolite morphine.Serious - Use Alternative (2)quinidine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  quinidine 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.

• ramelteon

  Monitor Closely (1)oxycodone and ramelteon both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)ramelteon and oxycodone both increase sedation. Avoid or Use Alternate Drug. Additive CNS depression may lead to hypotension, profound sedation, respiratory depression, or coma

• ranolazine

  Monitor Closely (1)ranolazine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• rasagiline

  Serious - Use Alternative (1)rasagiline increases toxicity of oxycodone by unknown mechanism. Avoid or Use Alternate Drug. May cause additive CNS depression, drowsiness, dizziness or hypotension, so use with MAOIs should be cautious; lower initial dosages of the analgesic are recommended followed by careful titration. Avoid combination within 14 days of MAOI use.

• remimazolam

  Monitor Closely (1)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

  Monitor Closely (1)ribociclib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  Monitor Closely (1)rifabutin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)rifabutin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• rifampin

  Monitor Closely (1)rifampin decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)rifampin decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• rifapentine

  Monitor Closely (1)rifapentine decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• risperidone

  Monitor Closely (1)oxycodone and risperidone both increase sedation. Use Caution/Monitor.

• ritonavir

  Serious - Use Alternative (2)ritonavir increases levels of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.
  
  ritonavir 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.

• rocuronium

  Monitor Closely (1)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

  Monitor Closely (1)rucaparib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rufinamide

  Minor (1)rufinamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• ruxolitinib

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ruxolitinib topical

  Minor (1)acetaminophen will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sage

  Minor (1)oxycodone and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (1)oxycodone increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• saquinavir

  Serious - Use Alternative (1)saquinavir 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.

• scullcap

  Monitor Closely (1)oxycodone and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (1)secobarbital and oxycodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)secobarbital will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May also enhance CNS depressant effect of oxycodone

• selegiline

  Monitor Closely (1)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.

• selegiline transdermal

  Serious - Use Alternative (1)selegiline transdermal increases toxicity of oxycodone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• selinexor

  Serious - Use Alternative (1)selinexor, oxycodone. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• sertraline

  Monitor Closely (2)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

  Monitor Closely (1)sevoflurane and oxycodone both increase sedation. Use Caution/Monitor.

• shepherd's purse

  Monitor Closely (1)oxycodone and shepherd's purse both increase sedation. Use Caution/Monitor.

• sodium oxybate

  Serious - Use Alternative (1)oxycodone, sodium oxybate. 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.

• St John's Wort

  Monitor Closely (1)St John's Wort decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• stiripentol

  Monitor Closely (2)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.
  
  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.

• succinylcholine

  Monitor Closely (1)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

  Monitor Closely (1)oxycodone and sufentanil both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Serious - Use Alternative (1)sufentanil SL, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. 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.

• suvorexant

  Serious - Use Alternative (1)suvorexant and oxycodone both increase sedation. Avoid or Use Alternate Drug. Additive CNS depression may lead to hypotension, profound sedation, respiratory depression, or coma

• tapentadol

  Monitor Closely (1)oxycodone and tapentadol both increase sedation. Use Caution/Monitor.

• tasimelteon

  Serious - Use Alternative (1)tasimelteon and oxycodone both increase sedation. Avoid or Use Alternate Drug. Additive CNS depression may lead to hypotension, profound sedation, respiratory depression, or coma

• tazemetostat

  Monitor Closely (2)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

  Monitor Closely (1)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.

• temazepam

  Monitor Closely (1)temazepam and oxycodone both increase sedation. Use Caution/Monitor.

• terbutaline

  Monitor Closely (1)oxycodone increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tetracaine

  Monitor Closely (1)tetracaine, acetaminophen. Other (see comment). Use Caution/Monitor. Comment: Monitor for signs of methemoglobinemia when methemoglobin-inducing drugs are coadministered.

• thioridazine

  Monitor Closely (2)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.Minor (1)thioridazine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• thiothixene

  Monitor Closely (1)oxycodone and thiothixene both increase sedation. Use Caution/Monitor.

• tiagabine

  Minor (1)tiagabine decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• ticagrelor

  Serious - Use Alternative (1)oxycodone will decrease the level or effect of ticagrelor 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 ticagrelor 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

• tinidazole

  Monitor Closely (1)acetaminophen will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  Monitor Closely (1)tipranavir will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)tipranavir 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.

• topiramate

  Monitor Closely (1)oxycodone and topiramate both increase sedation. Modify Therapy/Monitor Closely.Minor (1)topiramate decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• tramadol

  Monitor Closely (1)oxycodone and tramadol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, oxycodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• tranylcypromine

  Serious - Use Alternative (1)tranylcypromine increases toxicity of oxycodone by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• trazodone

  Monitor Closely (1)oxycodone and trazodone both increase sedation. Use Caution/Monitor.

• triazolam

  Monitor Closely (1)triazolam and oxycodone both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (1)triclofos and oxycodone both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (1)oxycodone and trifluoperazine both increase sedation. Use Caution/Monitor.

• trimipramine

  Monitor Closely (1)oxycodone and trimipramine both increase sedation. Use Caution/Monitor.

• triprolidine

  Monitor Closely (1)triprolidine and oxycodone both increase sedation. Use Caution/Monitor.

• tucatinib

  Serious - Use Alternative (1)tucatinib will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• valerian

  Serious - Use Alternative (1)valerian and oxycodone both increase sedation. Avoid or Use Alternate Drug.

• valproic acid

  Minor (1)valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

• vecuronium

  Monitor Closely (1)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

  Monitor Closely (1)venlafaxine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)venlafaxine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• vilazodone

  Monitor Closely (1)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.

• voriconazole

  Serious - Use Alternative (1)voriconazole 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.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• warfarin

  Monitor Closely (1)acetaminophen increases effects of warfarin by anticoagulation. Use Caution/Monitor.

• xylometazoline

  Monitor Closely (1)oxycodone increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• yohimbine

  Monitor Closely (1)oxycodone increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• zaleplon

  Serious - Use Alternative (1)zaleplon and oxycodone both increase sedation. Avoid or Use Alternate Drug. Additive CNS depression may lead to hypotension, profound sedation, respiratory depression, or coma

• ziconotide

  Monitor Closely (1)oxycodone and ziconotide both increase sedation. Use Caution/Monitor.Minor (1)ziconotide, oxycodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

• ziprasidone

  Monitor Closely (1)oxycodone and ziprasidone both increase sedation. Use Caution/Monitor.

• zolpidem

  Serious - Use Alternative (1)zolpidem and oxycodone both increase sedation. Avoid or Use Alternate Drug. Additive CNS depression may lead to hypotension, profound sedation, respiratory depression, or coma

• zonisamide

  Minor (1)zonisamide decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism increase levels of hepatotoxic metabolites.

• zotepine

  Monitor Closely (1)oxycodone and zotepine both increase sedation. Use Caution/Monitor.