Drug General Information (ID: DDILJ5R9U6)
Drug Name			Fingolimod		Drug Info		Entrectinib		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Selective Immunosuppressants				Multikinase Inhibitors
Structure

Mechanism of Fingolimod-Entrectinib Interaction (Severity Level: Major)
Additive immunosuppressive effects Click to Show/Hide Mechanism Graph
Drug Name		Fingolimod				Entrectinib
Mechanism 1		Immunosuppressive effects				Immunosuppressive effects
Key Mechanism Factor 1
		Factor Name		Immunosuppressive effects
		Factor Description		Immunosuppression is when your immune system is not functioning as it should. The immune system is made up of cells, tissues and organs that help the body fight off infections. If the immune system is suppressed, an infection that your body was able to control may become serious or even fatal.
Mechanism Description		Additive immunosuppressive effects by the combination of Fingolimod and Entrectinib
Increased risk of ventricular arrhythmias Click to Show/Hide Mechanism Graph
Drug Name		Fingolimod				Entrectinib
Mechanism 2		Prolong QT interval				Bradycardia
Key Mechanism Factor 2
		Factor Name		Ventricular arrhythmias
		Factor Description		Ventricular arrhythmias are abnormal heart rhythms that cause your heart's lower chambers to pump blood instead of pumping it. This can limit or stop your heart from supplying blood to your body. While some of these arrhythmias are harmless and do not cause symptoms, others can have serious, even fatal, effects on your body.
Mechanism Description		Increased risk of ventricular arrhythmias by the combination of Fingolimod and Entrectinib

Recommended Action
Management		The safety and efficacy of fingolimod in combination with antineoplastic, immunosuppressive, or immune-modulating agents have not been evaluated. Caution is advised during coadministration. A complete blood count is recommended prior to starting fingolimod if a recent one (i.e., within last 6 months) is not available. Fingolimod has not been studied in patients receiving drugs that can prolong the QT interval. Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, close monitoring is recommended during initiation of fingolimod treatment in patients receiving concomitant drugs that can prolong the QT interval, patients with significant QT prolongation (QTc >470 msec in females or >450 msec in males), or patients with relevant risk factors for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital QT prolongation).

References
1	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
2	FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Revised recommendations for cardiovascular monitoring and use of multiple sclerosis drug Gilenya (fingolimod).".