Drug Interactions between celecoxib / tramadol and rifapentine

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of tramadol, which is primarily metabolized by CYP450 3A4 and 2D6. Reduced opioid efficacy can occur, including opioid withdrawal in physically dependent patients. After discontinuing a CYP450 3A4 inducer, the tramadol plasma concentration will increase, which could increase and/or prolong opioid efficacy and adverse reactions, including seizures, serotonin syndrome, and respiratory depression. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: Caution is advised when tramadol is used with CYP450 3A4 inducers. Patients should be monitored for opioid efficacy and signs of withdrawal. If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath. If a CYP450 3A4 inducer is discontinued, monitor for seizures, serotonin syndrome, sedation, and respiratory depression. The prescribing information for the concomitant CYP450 3A4 inducers should be consulted for specific recommendations.

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.

MONITOR: Coadministration with rifapentine may decrease the plasma concentrations of drugs that are substrates of the CYP450 2C8, 2C9, and/or 3A4 isoenzymes. The mechanism is accelerated clearance due to induction of these isoenzymes by rifapentine. Enzyme activities may be induced within 4 days of the first dose and return to normal 14 days after discontinuation of rifapentine. In vitro and in vivo enzyme studies have suggested rifapentine induction potential to be less than that of rifampin but greater than that of rifabutin. In addition, the magnitude of induction is dependent on dose and dosing frequency.

MANAGEMENT: The possibility of a diminished therapeutic response to drugs that are known substrates of CYP450 2C8, 2C9, and/or 3A4 should be considered during coadministration with rifapentine. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs, particularly those with a narrow therapeutic range, whenever rifapentine is added to or withdrawn from therapy.