Drug Interactions between chloramphenicol and Duragesic

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of fentanyl, which is primarily metabolized by the isoenzyme. Increased fentanyl concentrations could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Conversely, discontinuation of a CYP450 3A4 inhibitor could decrease fentanyl plasma concentrations, decrease opioid efficacy, and possibly even lead to a withdrawal syndrome in patients who had developed physical dependence to fentanyl. In eleven healthy volunteers, coadministration of the potent inhibitor ritonavir (200 mg orally three times a day on day 1; 300 mg three times a day on day 2; one morning dose of 300 mg on day 3) and intravenous fentanyl (5 mcg/kg two hours after the afternoon dose of ritonavir on day 2) resulted in a 174% increase in fentanyl systemic exposure (AUC) and a 67% decrease in fentanyl clearance compared to administration of fentanyl alone (with placebo). No other formulations of fentanyl such as patches or buccal tablets were studied.

MANAGEMENT: Patients receiving fentanyl with potent or moderate CYP450 3A4 inhibitors should be carefully monitored, and dosage adjustments made accordingly as needed. This is particularly important when an inhibitor is added after a stable dose of fentanyl has been achieved. Some authorities recommend avoiding concomitant use of fentanyl during and for 2 weeks after treatment with itraconazole. Patients and/or their caregivers should be advised to seek medical attention if potential signs and symptoms of toxicity occur, such as dizziness, confusion, fainting, extreme sedation, unresponsiveness, bradycardia, slow or difficult breathing, and shortness of breath. When discontinuing CYP450 3A4 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. Patients treated with transdermal formulations of fentanyl should be cautioned that drug interactions and drug effects may be observed for a prolonged period beyond removal of the patch, as significant amounts of fentanyl are absorbed from the skin for 17 hours or more after the patch is removed.