purseMonitor Closely (1)oxycodone and shepherd's purse both increase sedation. Use Caution/Monitor.sodium oxybateSerious - 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 WortMonitor Closely (1)St John's Wort decreases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.stiripentolMonitor 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.succinylcholineMonitor 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.sufentanilMonitor Closely (1)oxycodone and sufentanil both increase sedation. Use Caution/Monitor.sufentanil SLSerious - 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.suvorexantSerious - 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 comatapentadolMonitor Closely (1)oxycodone and tapentadol both increase sedation. Use Caution/Monitor.tasimelteonSerious - 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 comatazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor 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.temazepamMonitor Closely (1)temazepam and oxycodone both increase sedation. Use Caution/Monitor.terbutalineMonitor Closely (1)oxycodone increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.thioridazineMonitor 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.thiothixeneMonitor Closely (1)oxycodone and thiothixene both increase sedation. Use Caution/Monitor.ticagrelorSerious - 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 tipranavirMonitor 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.topiramateMonitor Closely (1)oxycodone and topiramate both increase sedation. Modify Therapy/Monitor Closely.tramadolMonitor 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.tranylcypromineSerious - 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.trazodoneMonitor Closely (1)oxycodone and trazodone both increase sedation. Use Caution/Monitor.triazolamMonitor Closely (1)triazolam and oxycodone both increase sedation. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos and oxycodone both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)oxycodone and trifluoperazine both increase sedation. Use Caution/Monitor.trimipramineMonitor Closely (1)oxycodone and trimipramine both increase sedation. Use Caution/Monitor.triprolidineMonitor Closely (1)triprolidine and oxycodone both increase sedation. Use Caution/Monitor.tucatinibSerious - 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.valerianSerious - Use Alternative (1)valerian and oxycodone both increase sedation. Avoid or Use Alternate Drug.vecuroniumMonitor 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.venlafaxineMonitor 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.vilazodoneMonitor 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.voriconazoleSerious - 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.voxelotorSerious - 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.xylometazolineMonitor Closely (1)oxycodone increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)oxycodone increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.zaleplonSerious - 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 comaziconotideMonitor 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.ziprasidoneMonitor Closely (1)oxycodone and ziprasidone both increase sedation. Use Caution/Monitor.zolpidemSerious - 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 comazotepineMonitor Closely (1)oxycodone and zotepine both increase sedation. Use Caution/Monitor. >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 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