Oxycodone

CNS depressant that when combined with oxycodone increases risk of hypotension, respiratory depression, profound sedation, coma, and death.

Additive CNS depression increases risk of hypotension, respiratory depression, profound sedation, coma, and death. Concomitant use should be reserved for inadequate alternative options.

Concomitant use increases risk of respiratory depression due to actions at different CNS receptor sites.

Concomitant use increases risk of respiratory depression due to additive CNS effects at different receptor sites. Monitor closely for respiratory depression and sedation.

CYP3A4 inducer that decreases oxycodone plasma concentration, resulting in decreased efficacy or withdrawal syndrome; discontinuation may cause serious respiratory depression.

fentanyl, oxycodone ↑ fentanyl ↑ oxycodone Careful monitoring of therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with co-administration.

fentanyl, oxycodone ↑ fentanyl ↑ oxycodone Careful monitoring of therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with co-administration.

fentanyl, oxycodone ↑ fentanyl ↑ oxycodone Careful monitoring of therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with co-administration.

Narcotic analgesics metabolized by CYP3A: e.g., fentanyl, oxycodone ↑ fentanyl ↑ oxycodone Careful monitoring of therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with co-administration.

CYP3A4 inhibitor that increases oxycodone plasma concentration, resulting in increased or prolonged opioid effects including respiratory depression and sedation.

Coadministration may cause respiratory depression and sedation, sometimes resulting in death.

Alpha Blockers tamsulosin Analgesics methadone alfentanil, buprenorphine IV and sublingual, fentanyl, oxycodone, sufentanil Methadone: The potential increase in plasma concentrations of methadone when coadministered with itraconazole may increase the risk of serious cardiovascular events including QTc prolongation and torsade de pointes .

The label of the coadministered drug should be consulted for information on dose adjustment and adverse effects Alpha Blockers tamsulosin Analgesics methadone alfentanil, buprenorphine IV and sublingual, fentanyl, oxycodone, sufentanil Methadone: The potential increase in plasma concentrations of methadone when coadministered with ketoconazole tablets may increase the risk of serious cardiovascular events including QT prolongation and torsade de pointes, or respiratory or CNS depression [See CONTRAINDICATIONS .] Fentanyl: The potential increase in plasma concentrations of fentanyl when coadministered with ketoconazole tablets may increase the risk of potentially fatal respiratory depression.

Narcotic analgesics metabolized by CYP3A: e.g., fentanyl, oxycodone ↑ fentanyl ↑ oxycodone Careful monitoring of therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with co-administration.

Narcotic analgesics fentanyl, hydrocodone, oxycodone, meperidine ↑ fentanyl ↑ hydrocodone ↑ oxycodone ↑ meperidine Careful monitoring of therapeutic and adverse effects (including potentially fatal respiratory depression) is recommended when fentanyl, hydrocodone, oxycodone, or meperidine is concomitantly administered with PAXLOVID.

Discontinue Oxycodone hydrochloride oral solution if serotonin syndrome is suspected. ( 7 ) Monoamine Oxidase Inhibitors (MAOIs): Can potentiate the effects of oxycodone. ( 7 ) Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with Oxycodone hydrochloride oral solution because they may reduce analgesic effect of Oxycodone hydrochloride oral solution or precipitate withdrawal symptoms.

CYP3A4 inducer that decreases oxycodone plasma concentration, resulting in decreased efficacy or withdrawal syndrome; discontinuation may cause serious respiratory depression.

Decrease AUC by 56% Narcotic Analgesics Oxycodone Decrease AUC by 86% Morphine Decrease exposure Selective 5-HT3 Receptor Antagonists Ondansetron Decrease exposure Statins Metabolized by CYP3A4 Simvastatin Decrease exposure Thiazolidinediones Rosiglitazone Decrease AUC by 66% Tricyclic Antidepressants Nortriptyline i Decrease exposure Other Drugs Enalapril Decrease active metabolite exposure Chloramphenicol j Decrease exposure Clarithromycin Decrease exposure Dapsone Decrease exposure Doxycycline k Decrease exposure Irinotecan l Prevention or Management: Avoid the use of rifampin, strong CYP3A4 inducer, if possible.

Protease inhibitor and CYP3A4 inhibitor that increases oxycodone plasma concentration, resulting in increased or prolonged opioid effects including respiratory depression and sedation.

Additive effects on cognitive and gross motor functioning observed when co-administered with pregabalin.

Additive effects on cognitive and gross motor functioning when co-administered with pregabalin.

Mixed agonist/antagonist and partial agonist opioids may reduce analgesic effect of tapentadol and/or precipitate withdrawal symptoms. Concomitant use should be avoided.

If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydrocodone, oxymorphone, hydrocodone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydrocodone, oxymorphone, hydromorphone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydrocodone, oxymorphone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydrocodone, oxymorphone, hydrocodone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydrocodone, oxymorphone, hydrocodone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

ketoconazole), and protease inhibitors (e.g., ritonavir), can increase the plasma concentration of oxycodone, resulting in increased or prolonged opioid effects. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodone plasma concentration will decrease [see CLINICAL PHARMACOLOGY ] , resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to ENDOCET. Inducers of CYP3A4 The concomitant use of ENDOCET and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of oxycodone [see CLINICAL PHARMACOLOGY ] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to ENDOCET [see WARNINGS ] .

Drug -Drug Interactions (see PRECAUTIONS) Inhibitors of CYP3A4 Since the CYP3A4 isoenzyme plays a major role in the metabolism of oxycodone and aspirin tablets, drugs that inhibit CYP3A4 activity, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may cause decreased clearance of oxycodone, which could lead to an increase in oxycodone plasma concentrations. A published study showed that the co-administration of the antifungal drug, voriconazole, increased oxycodone AUC and Cmax by 3.6 and 1.7 fold, respectively. Inducers of CYP450 CYP450 inducers, such as rifampin, carbamazepine, and phenytoin, may induce the metabolism of oxycodone, may cause increased clearance of the drug which could lead to a decrease in oxycodone plasma concentrations.

Drug Interactions Inhibitors of CYP3A4 and CYP2D6 The concomitant use of oxycodone hydrochloride and acetaminophen oral solution and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g., ritonavir), can increase the plasma concentration of oxycodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of oxycodone hydrochloride and acetaminophen oral solution and CYP3A4 and CYP2D6 inhibitors, particularly when an inhibitor is added after a stable dose of oxycodone hydrochloride and acetaminophen oral solution is achieved [see WARNINGS ].

7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with Oxycodone Hydrochloride Oral Solution. Table 1: Clinically Significant Drug Interactions with Oxycodone Hydrochloride Oral Solution Inhibitors of CYP3A4 and CYP2D6 Clinical Impact: The concomitant use of Oxycodone Hydrochloride Oral Solution and CYP3A4 inhibitors can increase the plasma concentration of oxycodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of Oxycodone Hydrochloride Oral Solution and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of Oxycodone Hydrochloride Oral Solution is achieved [see Warnings and Precautions (5.6) ].

Oxycodone (CYP3A4 Inhibition) Significantly Increased Increased visual effects (heterophoria and miosis) of oxycodone were observed when concomitantly administered with VFEND. Reduction in the dose of oxycodone and other long-acting opiates metabolized by CYP3A4 should be considered when concomitantly administered with VFEND.