Drug Interactions between rifabutin and ropivacaine / sufentanil

MONITOR CLOSELY: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of opioids that are primarily metabolised by the isoenzyme such as butorphanol, fentanyl, hydrocodone, and oxycodone. Reduced efficacy or withdrawal symptoms may occur in patients maintained on their narcotic pain regimen following the addition of a CYP450 3A4 inducer. Conversely, discontinuation of the inducer may increase opioid plasma concentrations and potentiate the risk of overdose and fatal 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: Pharmacologic response to the opioid should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the opioid dosage adjusted as necessary. 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.

Rifampin or other rifamycins may decrease the plasma concentrations of ropivacaine. The mechanism is rifamycin induction of CYP450 1A2 and 3A4, the isoenzymes responsible for the metabolic clearance of ropivacaine. In 18 healthy volunteers, rifampin (600 mg once a day for 5 days) increased the mean area under the plasma concentration-time curve of a single 0.6 mg/kg IV dose of ropivacaine by 52% and 38% in nonsmokers and smokers, respectively, compared to placebo. In nonsmokers, rifampin increased the clearance of ropivacaine by 93% and shortened its half-life by 25%. In smokers, rifampin increased the clearance of ropivacaine by 47% and shortened its half-life by 20%. The reduced effect of rifampin seen in smokers may be due to induction of ropivacaine metabolism via CYP450 1A2 caused by smoking. In clinical practice, the interaction should have minimal impact on the quality and duration of local anesthesia produced by ropivacaine, since induction of CYP enzymes is not likely to affect local anesthetic before it enters the systemic blood circulation.