Drug General Information (ID: DDIBUHJ90V)
Drug Name			Methotrexate		Drug Info		Regorafenib		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antimetabolites				Vegf/Vegfr Inhibitors
Structure

Mechanism of Methotrexate-Regorafenib Interaction (Severity Level: Moderate)
Increased risk of hepatotoxicity Click to Show/Hide Mechanism Graph
Drug Name		Methotrexate				Regorafenib
Mechanism		Hepatotoxicity				Hepatotoxicity
Key Mechanism Factor 1
		Factor Name		Hepatotoxicity
		Factor Description		Combination of drugs that can induce hepatotoxicity may increase the risk of liver injury. Symptoms vary depending on the level of exposure and the total extent of liver damage, and may cause few symptoms if the damage is mild, and eventually lead to liver failure in patients with severe damage.
Mechanism Description		Increased risk of hepatotoxicity by the combination of Methotrexate and Regorafenib

Recommended Action
Management		The use of methotrexate with other potentially hepatotoxic agents should be avoided whenever possible. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, pale stools, and jaundice. Baseline and regular monitoring of hepatic function is recommended. Caution is recommended when regorafenib is used in combination with BCRP inhibitors such as methotrexate. Monitoring for signs and symptoms of increased exposure to the BCRP substrate should be considered whenever regorafenib is added to or withdrawn from therapy.

References
1	Cerner Multum, Inc. "Australian Product Information.".
2	Cerner Multum, Inc. "Canadian Product Information.".
3	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4	Product Information. Methotrexate (methotrexate). Lederle Laboratories, Wayne, NJ.
5	Product Information. Stivarga (regorafenib). Bayer Pharmaceutical Inc, West Haven, CT.