oxycodone/naltrexone (Discontinued)

Brand and Other Names:Troxyca ER
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

oxycodone/naltrexone

extended-release capsule

  • 10mg/1.2mg
  • 20mg/2.4mg
  • 30mg/3.6mg
  • 40mg/4.8mg
  • 60mg/7.2mg
  • 80mg/9.6mg

Chronic Pain

Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

To be prescribed only by healthcare providers knowledgeable in use of potent opioids for management of chronic pain

Opioid-naïve or nonopioid-tolerant patients

  • Starting dose: 10 mg/1.2 mg PO q12hr
  • Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression

Dose titration

  • Individually titrate dose to provide adequate analgesia and minimal adverse effects
  • Steady-state plasma concentrations are achieved within 48 hr
  • May be up-titrated from current dose by increasing daily dose in increments of 20 mg/2.4 mg per day q2-3 days as needed based on efficacy, safety, and tolerability
  • If breakthrough pain experienced, assess need for a dosage increase or a rescue dose of an immediate-release analgesic

Opioid-tolerant patients

  • See Administration section for conversion from other PO oxycodone formulations or other opioids to Troxyca ER
  • Patients who are opioid tolerant are those receiving the following for ≥1 week
    • ≥60 mg/day PO morphine
    • ≥25 mcg/hr transdermal fentanyl
    • ≥30 mg/day PO oxycodone
    • ≥8 mg/day PO hydromorphone
    • ≥25 mg/day PO oxymorphone, OR
    • Equianalgesic dose of another opioid

Dosage Modifications

Hepatic impairment

  • Oxycodone is extensively metabolized in the liver; initiate therapy conservatively and titrate slowly
  • Naltrexone is sequestered in the capsules and is typically not released when used as directed (ie, not crushed, chewed, or dissolved); however, an increased naltrexone AUC has been observed with compensated and decompensated liver cirrhosis
  • Monitor for CNS or respiratory depression due to increased oxycodone levels and for signs of withdrawal attributed to elevated naltrexone levels

Renal impairment

  • Oxycodone elimination is reduced in renal impairment; initiate therapy conservatively and titrate slowly
  • Naltrexone is sequestered in the capsules and is typically not released when used as directed (ie, not crushed, chewed, or dissolved); however, measurable naltrexone plasma levels have been observed in some patients
  • Since naltrexone and its primary metabolite are primarily excreted in the urine, their plasma concentration may increase with renal impairment
  • Monitor for CNS or respiratory depression due to increased oxycodone levels and for signs of withdrawal attributed to elevated naltrexone levels

Dosing Considerations

Not indicated as prn analgesic

<18 years: Safety and efficacy not established

Drug is substantially excreted in the urine; cautious, conservative use is advised with use in elderly individuals

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Interactions

Interaction Checker

and oxycodone/naltrexone

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            Contraindicated (1)

            • alvimopan

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

            Serious - Use Alternative (42)

            • abametapir

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

            • amobarbital

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

            • apalutamide

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

            • artemether/lumefantrine

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

            • atazanavir

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

            • benzhydrocodone/acetaminophen

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

            • bremelanotide

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

              bremelanotide will decrease the level or effect of naltrexone 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 using bremelanotide with an orally administered naltrexone-containing product that is intended to treat alcohol and opioid addiction due to the potential for naltrexone treatment failure.

            • 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.

            • naldemedine

              naldemedine, naltrexone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive opioid receptor anatagonism and increased risk of opioid withdrawal.

            • buprenorphine buccal

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

            • butorphanol

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

            • calcium/magnesium/potassium/sodium oxybates

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

            • cimetidine

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

            • clarithromycin

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

            • clonidine

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

            • conivaptan

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

            • diazepam intranasal

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

            • eluxadoline

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

            • eszopiclone

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

            • fentanyl

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

            • fentanyl intranasal

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

            • fentanyl transdermal

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

            • fentanyl transmucosal

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

            • 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.

            • 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.

            • 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.

            • naloxegol

              naloxegol, naltrexone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration; potential for additive effect of opioid receptor anatagonism and increased risk of opioid withdrawal.

            • 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.

            Monitor Closely (148)

            • acamprosate

              naltrexone increases levels of acamprosate by unspecified interaction mechanism. Use Caution/Monitor. No dosage adjustment is needed.

            • 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 naltrexone by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

            • apomorphine

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

            • arformoterol

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

            • aripiprazole

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

            • armodafinil

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

            • asenapine

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

            • atracurium

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

            • 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.

            • 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.

            • butabarbital

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

            • butalbital

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

            • butorphanol

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

            • caffeine

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

            • carbamazepine

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

            • carbinoxamine

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

            • carisoprodol

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

            • celecoxib

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

            • cenobamate

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

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

            • chloral hydrate

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

            • chloramphenicol

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

            • chlordiazepoxide

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

            • chloroquine

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

            • chlorpheniramine

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

            • chlorpromazine

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

            • chlorzoxazone

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

            • cimetidine

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

            • cinnarizine

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

            • cisatracurium

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

            • citalopram

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

            • clemastine

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

            • clobazam

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

            • clomipramine

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

            • clonazepam

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

            • clorazepate

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

            • clozapine

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

            • cobicistat

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

            • codeine

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

            • crizotinib

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

            • crofelemer

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

            • cyclizine

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

            • cyclobenzaprine

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

            • cyproheptadine

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

            • dabrafenib

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

            • dantrolene

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

            • 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.

            • dronabinol

              naltrexone increases effects of dronabinol by Other (see comment). Use Caution/Monitor. Comment: Naltrexone may enhance therapeutic effects of cannabinoids. .

            • 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 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.

            • 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.

            • 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.

            • flibanserin

              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.

            • 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.

            • 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.

            • 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.

            • 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.

            • lofepramine

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

            • lofexidine

              lofexidine will decrease the level or effect of naltrexone by unknown mechanism. Modify Therapy/Monitor Closely. Coadministration of lofexidine with oral naltrexone resulted in statistically significant differences in the steady-state pharmacokinetics of naltrexone. The efficacy of oral naltrexone may be reduced if administered within 2 hours of taking lofexidine. Interaction not expected with other naltrexone routes of administration.

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

            • loprazolam

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

            • nabilone

              naltrexone increases effects of nabilone by Other (see comment). Use Caution/Monitor. Comment: Naltrexone may enhance therapeutic effects of cannabinoids. .

            Minor (18)

            • amiodarone

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

            • brimonidine

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

            • 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.

            • dextroamphetamine

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

            • diphenhydramine

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

            • eucalyptus

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

            • haloperidol

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

            • imatinib

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

            • lidocaine

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

            • 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.

            • propafenone

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

            • quinacrine

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

            • 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.

            • 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.

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            Adverse Effects

            >10%

            Nausea (14.4-20.5%)

            Constipation (3.4-14.9%)

            1-10%

            Vomiting (6.2-9%)

            Somnolence (0.7-9%)

            Headache (1.4-7.3%)

            Pruritus (2.1-6.6%)

            Dizziness (4.1-5.9%)

            Diarrhea (2.2-5.5%)

            Dry mouth (3.2%)

            Fatigue (3.2-3.4%)

            Abdominal pain (1.4-2.9%)

            Hyperhidrosis (2.4-2.7%)

            Drug withdrawal symptoms (1-2.7%)

            Muscle spasms (0.2-2.7%)

            Hot flush (1.4-2.4%)

            Back pain (1.2-2.1%)

            Edema, peripheral (0.7-2.1%)

            Arthralgia (0.7-2.1%)

            Hypoesthesia (0-2.1%)

            Oropharyngeal pain (0-2.1%)

            Insomnia (0.7-2%)

            Postmarketing Reports

            Serotonin syndrome

            Adrenal insufficiency; mostly with use exceeding 1 month

            Anaphylaxis and pharyngeal edema

            Androgen deficiency with long-term use

            Myocardial ischemia and ventricular fibrillation reported with overdose

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            Warnings

            Black Box Warnings

            Addiction, abuse, and misuse

            • Exposes patients and other users to risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
            • Assess patient’s risk prior to prescribing and monitor regularly for the development of these behaviors and conditions

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur
            • Monitor for respiratory depression, especially during initiation of, or following, a dose increase
            • Instruct patients to swallow capsules whole or to sprinkle capsule contents on applesauce and swallow immediately without chewing
            • Crushing, chewing, or dissolving can cause rapid release and absorption of a potentially fatal oxycodone dose

            Accidental ingestion

            • Accidental ingestion of even 1 dose, especially by children, can result in a fatal oxycodone overdose

            Neonatal opioid withdrawal syndrome

            • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated with management by neonatology experts
            • If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            CYP3A4 interaction

            • Coadministration with all CYP3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and lead to respiratory depression
            • Additionally, discontinuation of concomitantly used CYP3A4 inducers may result in increased oxycodone plasma concentrations
            • Monitor closely if coadministered with CYP3A4 inhibitors or inducers
            • Also see Cautions and Drug Interactions

            Interaction with central nervous system (CNS) depressants

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

            Contraindications

            Patients with significant respiratory depression

            Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment

            Known or suspected GI obstruction, including paralytic ileus

            Hypersensitivity (eg, anaphylaxis) to oxycodone or naltrexone or any other components of the formulation

            Cautions

            Contains oxycodone, a Schedule II controlled drug; as an opioid, oxycodone/naltrexone exposes users to the risks of addiction, abuse, and misuse; as extended-release products (eg, Troxyca ER) deliver the opioid over an extended period, there is a greater risk for overdose and death owing to the larger amount of oxycodone present (see Black Box Warnings)

            Prolonged use during pregnancy can result in neonatal withdrawal syndrome that may be fatal if not recognized and managed by neonatal experts (see Black Box Warnings)

            Adrenal insufficiency reported with opioid use (greater incidence if used >1 month); if adrenal insufficiency diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid

            Severe hypotension reported, including orthostatic hypotension and syncope in ambulatory patients; risk increases in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazine, general anesthetics); monitor for severe hypotension during dosage initiation and titration; avoid use with circulatory shock

            Oxycodone/naltrexone may further reduce respiratory drive and exacerbate CO2 retention in patients with increased ICP or brain tumors; may also obscure the clinical course in a patient with a head injury; avoid use with impaired consciousness or coma

            Contraindicated with GI obstruction (see Contraindications); oxycodone may cause spasm of the sphincter of Oddi and increase serum amylase; monitor with biliary tract disease, including acute pancreatitis, for worsening symptoms

            May increase risk of seizures; monitor with history of seizure disorders for worsened seizure control during therapy

            Altering the drug by crushing, chewing, or dissolving the pellets within the capsule can release sufficient naltrexone to precipitate withdrawal in opioid-dependent individuals

            Gradually discontinue; do not stop drug abruptly (see Administration)

            May impair mental or physical abilities needed to drive or operate machinery

            Naltrexone does not interfere with thin-layer, gas-liquid, or high-pressure liquid chromatography for detection of morphine, methadone, oxycodone, or quinine in urine; naltrexone may or may not interfere with enzymatic methods for detecting opioids, depending on the sensitivity and specificity of the test

            Respiratory depression

            • Serious, life-threatening, or fatal respiratory depression has been reported with opioids, even when used as recommended; risk is greatest when initiating treatment or after increasing the dose
            • Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered drug clearance compared with younger, healthier patients
            • Patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression, are at increased risk of decreased respiratory drive, including apnea, even at recommended dosages
            • Monitor these patients closely, particularly when initiating and titrating oxycodone/naltrexone, or if coadministered with other drugs that depress respiration; alternatively, consider using nonopioid analgesics
            • Also see Black Box Warnings

            Drug interaction overview

            • CYP3A4 inhibitors and inducers
              • Oxycodone is a CYP3A4 and CYP2D6 substrate
              • Coadministration with CYP3A4 inhibitors (eg, macrolide antibiotics, azole antifungal agents, protease inhibitors) may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression, particularly when a CYP3A4 inhibitor is added after a stable dose of oxycodone/naltrexone is achieved
              • Similarly, discontinuation of a CYP3A4 inducer (eg, rifampin, carbamazepine, phenytoin) in oxycodone/naltrexone-treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions
              • When coadministering CYP3A4 inhibitors or discontinuing CYP3A4 inducers, monitor patients closely at frequent intervals and consider oxycodone/naltrexone dosage reduction until stable drug effects are achieved
              • These effects may be more pronounced with drugs that inhibit both CYP3A4 and CYP2D6
              • Coadministration with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone
              • When coadministering CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur
              • Also see Black Box Warnings
            • CNS depressants
              • Hypotension, profound sedation, respiratory depression, coma, and death may result if coadministered with alcohol or other CNS depressants (eg, benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids)
              • Assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression
              • Also evaluate alcohol use or illicit drug use
              • If the decision to begin oxycodone/naltrexone is made, start with a lower dosage, monitor patients for signs of respiratory depression, sedation, and hypotension, and consider using a lower dose of the concomitant CNS depressant
            • Serotonergic drugs
              • Coadministration of opioids with other drugs (eg, SSRIs, SNRIs, TCAs, triptans, 5-HT3 antagonists, mirtazapine, trazodone, tramadol, MAOIs, linezolid, methylene blue) that affect the serotonergic neurotransmitter system may result in serotonin syndrome
              • If coadministration is warranted, carefully monitor, especially during treatment initiation or dose adjustment
              • Discontinue drug if serotonin syndrome suspected or evident
            • Mixed agonist/antagonists and partial agonist opioid analgesics
              • Coadministration may precipitate withdrawal
              • Avoid use with mixed agonist/antagonist (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics
            • Muscle relaxants
              • Opioids may enhance neuromuscular blockade and increase respiratory depression
              • Monitor for respiratory depression that may be more than expected with muscle relaxants; decrease dose of opioid, muscle relaxant, or both
            • Monoamine oxidase inhibitors (MAOIs)
              • Coadministration with MAOIs can potentiate oxycodone effects and increase risk of anxiety, confusion, hypotension, respiratory depression, profound sedation, coma, and death
              • Avoid concomitant use with MAOIs or within 14 days of stopping an MAOI
            • Diuretics
              • Opioids can decrease diuretic efficacy by inducing antidiuretic hormone release
              • Monitor for decreased diuresis and/or effects on blood pressure Increase diuretic dose as needed
            • Anticholinergic drugs
              • Coadministration may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus
              • Monitor for signs of urinary retention or reduced GI motility
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            Pregnancy & Lactation

            Pregnancy

            Prolonged use during pregnancy may cause neonatal opioid withdrawal syndrome (see Black Box Warnings)

            Lactation

            Oxycodone is present in breast milk; because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, breastfeeding is not recommended during treatment with oxycodone/naltrexone

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Opioid agonist/opioid antagonist combination product

            Oxycodone: Opioid agonist; relatively selective for the mu receptor, but it can bind to other opioid receptors at higher doses; inhibits ascending pain pathways, thus altering response to pain; produces analgesia, respiratory depression, and sedation

            Naltrexone: Opioid competitive receptor antagonist; shows highest affinity for mu receptors

            Absorption

            Bioavailability: 60-87% (oxycodone)

            Peak plasma time: 12 hr (oxycodone)

            Peak plasma concentration: Reduced by ~67% compared with immediate-release IR oxycodone

            AUC: Equivalent to immediate-release oxycodone

            Steady-state: Reached in 48 hr

            Crushed capsule

            • Analgesic activity primarily due to the parent drug oxycodone; oxycodone/naltrexone is designed to provide delivery of oxycodone over 12 hr
            • Chewing, crushing, or dissolving the pellets within the capsules impairs the extended-release delivery mechanism and results in the rapid release and absorption of a potentially FATAL dose of oxycodone and a potentially complete release of sequestered naltrexone
            • Peak plasma time (crushed capsule): 0.6-1 hr PO; 1.6 hr intranasal

            Distribution

            Vd: 2.6 L/kg

            Protein bound: ~45%

            Metabolism

            Oxycodone is extensively metabolized to noroxycodone, oxymorphone, and their glucuronides

            CYP3A-mediated N-demethylation to an in active metabolite from noroxycodone is the principal metabolic pathway of oxycodone in humans

            CYP2D6-mediated O-demethylation to an active metabolite oxymorphone is a minor metabolic pathway

            Elimination

            Half-life: ~7.2 hr (oxycodone)

            Total plasma clearance: 0.8 L/min

            Urinary excretion: 19% (free oxycodone); 50% (conjugated oxycodone); ~14% (conjugated oxymorphone)

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            Administration

            Oral Administration

            Swallow capsule whole

            Instruct patients not to crush, chew, or dissolve the pellets in the capsule to avoid the risk of release and absorption of a potentially fatal dose of oxycodone and to avoid release of sequestered naltrexone that could precipitate opioid withdrawal

            Alternatively, the capsule contents (ie, pellets) may be sprinkled on a small amount of applesauce (other foods have not been tested) and swallowed immediately without chewing; rinse mouth with water and swallow to ensure all pellets have been swallowed

            Do not administer pellets through NG or G-tube

            Discontinuation

            • Do not abruptly discontinue
            • Taper the dose gradually, by 25-50% q2-4 days, while monitoring carefully for signs and symptoms of withdrawal
            • If withdrawal signs or symptoms occur, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both

            Opioid Tolerant Patients

            60 mg/7.2 mg and 80 mg/9.6 mg capsules, single doses >40 mg/4.8 mg, or a total daily dose >80 mg/9.6 mg are only for patients in whom tolerance to an opioid of comparable potency has been established

            Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals

            Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse

            Conversion from other PO oxycodone

            • Patients receiving other oral oxycodone formulations may be converted to oxycodone/naltrexone by administering 50% of the patient’s total daily PO oxycodone dose as Troxyca ER q12hr

            Conversion from other opioids

            • Discontinue all other around-the-clock opioid drugs when initiating oxycodone/naltrexone
            • When converting patients to oxycodone/naltrexone, it is safer to underestimate a patient’s 24-hr oral oxycodone requirements and provide rescue medication (eg, immediate-release opioid) than to overestimate the 24-hr oral oxycodone requirements, which could result in adverse reactions
            • Conversion factors to oxycodone
              • Codeine: 0.1
              • Hydrocodone: 0.67
              • Hydromorphone: 2.67
              • Morphine: 0.67
              • Oxycodone: 1
            • Calculate ~total daily PO oxycodone dose
              • Multiply current total daily dose of the opioid by the conversion factor listed above by appropriate conversion factor (if >1 opioid, calculate total daily for each opioid factor and add the sum totals)
              • Use only the opioid component to calculate total daily dose of combination opioid/nonopioid analgesics
              • Reduce the estimated total daily oxycodone dose by 50% to obtain the daily dose of Troxyca ER; divide this daily dose in half to obtain the q12hr dose
              • After conversion, if the total daily opioid requirement is ≤20 mg/day of oxycodone, initiate with Troxyca ER 10 mg/1.2 mg q12hr
              • Always round the dose down, if necessary, to the appropriate Troxyca ER strength
              • Provide prompt-acting rescue analgesic as needed (eg, immediate-release oxycodone)
              • Reevaluate total daily dose (scheduled plus short-acting rescue medication) to adjust dose; additionally, monitor for any signs of opioid withdrawal
            • Conversion example
              • Hydrocodone extended-release 30 mg PO q12hr = 60 mg/day
              • 60 mg hydrocodone x 0.67 (conversion factor) = oxycodone 40.2 mg/day
              • Oxycodone 40.2 mg/day reduced by 50% ~20 mg/day
              • Divided 20 mg/day in half to obtain the q12hr Troxyca ER dose; for this example, it would be 10 mg/1.2 mg PO q12hr

            Conversion from methadone

            • Close monitoring is essential when converting from methadone to other opioid agonists
            • The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure

            Conversion from transdermal fentanyl

            • May initiate oxycodone/naltrexone 18 hr after removing transdermal fentanyl patch
            • A conservative estimated dose of 10 mg/1.2 mg PO q12hr oxycodone/naltrexone should be substituted for each 25-mcg/hr fentanyl patch
            • Monitor closely during conversion; limited documented experience with this conversion

            Conversion from transdermal buprenorphine

            • There has been no systematic assessment of this conversion
            • Initiate oxycodone/naltrexone 10 mg/1.2 mg PO q12hr
            • Monitor closely during conversion; limited documented experience with this conversion

            Conversion from tramadol

            • Tramadol has both serotonergic and opioid activity, and there has been no systematic assessment of this conversion
            • Initiate oxycodone/naltrexone 10 mg/1.2 mg PO q12hr
            • Monitor closely during conversion; limited documented experience with this conversion

            Storage

            Store at 25°C (77°F); excursions permitted from 15-30°C (59-86°F)

            Dispense in tight (USP), light-resistant, child-resistant containers

            Instruct patients to take steps to store securely and dispose of unused drug by flushing the capsules down the toilet

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            Patient Handout

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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.