Drug General Information (ID: DDIBKIE25R)
Drug Name			Buprenorphine		Drug Info		Entrectinib		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Analgesics				Multikinase Inhibitors
Structure

Mechanism of Buprenorphine-Entrectinib Interaction (Severity Level: Moderate)
Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Drug Name		Buprenorphine				Entrectinib
Mechanism		Prolong QT interval				Prolong QT interval
Key Mechanism Factor 1
		Factor Name		QT interval
		Factor Description		Long QT syndrome is a heart signaling disorder that can cause a fast, chaotic heartbeat (arrhythmia). Many people may not exhibit symptoms, and usually the condition is detected during routine medical tests. In others, the most common symptoms include: sudden fainting, palpitations, dizziness, seizures, sudden death.
Mechanism Description		Increased risk of prolong QT interval by the combination of Buprenorphine and Entrectinib

Recommended Action
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pharmacologic response and vital signs should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the buprenorphine dosage adjusted as necessary.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.

References
1	Canadian Pharmacists Association.
2	Cerner Multum, Inc. "Australian Product Information.".
3	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4	Demolis JL, Vacheron F, Cardus S, Funck-Brentano C "Effect of single and repeated oral doses of telithromycin on cardiac QT interval in healthy subjects." Clin Pharmacol Ther 73 (2003): 242-52. [PMID: 12621389]
5	European Medicines Agency "CHMP Assessment Report for Latixa. International nonproprietary name: ranolazine.".
6	Product Information. Belbuca (buprenorphine). Endo Pharmaceuticals Solutions Inc, Malvern, PA.
7	Product Information. Buprenex (buprenorphine). Reckitt and Colman Pharmaceutical, Richmond, VA.
8	Product Information. Butrans (buprenorphine). Purdue Pharma LP, Stamford, CT.
9	Product Information. Ketek (telithromycin). Aventis Pharmaceuticals, Bridgewater, NJ.
10	Product Information. Ranexa (ranolazine). Calmoseptine Inc, Huntington Beach, CA.
11	Product Information. Sprycel (dasatinib). Bristol-Myers Squibb, Princeton, NJ.
12	European Agency for the Evaluation of Medicinal Products. Committee for Proprietary Medicinal Products "European Public Assessment Report Ketek (telithromycin) (Rev. 2) ".