Drug Interactions between buprenorphine and Phyrago

GENERALLY AVOID: Buprenorphine can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations and pharmacologic effects of buprenorphine, which is partially metabolized (approximately 30%) by the isoenzyme. The interaction appears to be dependent, in part, on the route of administration of buprenorphine. When administered transdermally, buprenorphine peak plasma concentration (Cmax) and systemic exposure (AUC) were not significantly affected by ketoconazole, a potent CYP450 3A4 inhibitor. However, it was reported in another study that ketoconazole increased the Cmax and AUC of buprenorphine (route unspecified) by approximately 70% and 50%, respectively, and to a lesser extent, of the metabolite norbuprenorphine.

MANAGEMENT: Coadministration of buprenorphine with other drugs that can prolong the QT interval and are CYP450 3A4 inhibitors should generally be avoided. Since the magnitude of QT prolongation may increase with increasing plasma concentrations of buprenorphine, caution and close clinical monitoring are recommended if concomitant use with these drugs is unavoidable. Induction with buprenorphine should begin at a reduced dosage, and dosage escalation should occur more slowly to allow for assessment of opiate effects and development of patient tolerance. In patients who are already stabilized on buprenorphine, pharmacologic response and vital signs should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the buprenorphine dosage adjusted as necessary. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. In addition, patients should seek medical attention if potential signs and symptoms of buprenorphine toxicity occur such as confusion, extreme sedation, or slow or difficult breathing.