Drug General Information (ID: DDI3XQRG1K)
Drug Name			Nabumetone		Drug Info		Inotersen		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Nsaids/Analgesics				Metabolic Agents
Structure

Mechanism of Nabumetone-Inotersen Interaction (Severity Level: Major)
Increased risk of bleeding Click to Show/Hide Mechanism Graph
Drug Name		Nabumetone				Inotersen
Mechanism 1		Risk of bleeding Antiplatelet effects				Risk of bleeding Antiplatelet effects
Key Mechanism Factor 1
		Factor Name		Bleeding
		Factor Description		Patients may be at risk for bleeding when the outcome of a disease or disease treatment confounds the standard mechanisms for maintaining hemostasis. Signs or symptoms of abnormal bleeding include: bleeding that takes a long time to stop (including nosebleeds, bleeding gums, bleeding from cuts and abrasions, and menstrual bleeding); severe unexplained bruising, or bruising that becomes larger; blood in the urine or stool, etc.
Mechanism Description		Increased risk of bleeding by the combination of Nabumetone and Inotersen
Increased risk of nephrotoxicity Click to Show/Hide Mechanism Graph
Drug Name		Nabumetone				Inotersen
Mechanism 2		Nephrotoxicity				Nephrotoxicity
Key Mechanism Factor 2
		Factor Name		Nephrotoxicity
		Factor Description		The combination of drugs that can induce nephrotoxicity may increase the risk of kidney injury. When kidney injury occurs, the inability to remove excess urine and waste from the body can lead to high levels of urea nitrogen, creatinine, and electrolytes (such as potassium and magnesium) in the blood.
Mechanism Description		Increased risk of nephrotoxicity by the combination of Nabumetone and Inotersen

Recommended Action
Management		Caution is advised when inotersen is prescribed with NSAIDs. A platelet count should be obtained prior to initiation of inotersen and regularly during and for at least 8 weeks after treatment in accordance with the product labeling. Inotersen should not be administered in patients with a platelet count below 100 x 10^9/L or in patients who are unable to adhere to the recommended laboratory monitoring and management guidelines. Patients or their caregivers should be apprised of the signs and symptoms of thrombocytopenia and to seek medical attention if they occur, including any unusual or prolonged bleeding (e.g., petechiae, easy bruising, hematoma, subconjunctival bleeding, gingival bleeding, epistaxis, hemoptysis, irregular or heavier than normal menstrual bleeding, hematemesis, hematuria, hematochezia, melena), neck stiffness, or atypical severe headache. Caution is advised when inotersen is prescribed with high dosages and/or chronic use of NSAIDs. Serum creatinine, estimated glomerular filtration rate (eGFR), urine protein to creatinine ratio (UPCR), and a urinalysis should be obtained prior to initiation of inotersen and regularly during and for at least 8 weeks after treatment in accordance with the product labeling. Inotersen should generally not be initiated in patients with a UPCR of 1000 mg/g or higher, or in patients who are unable to adhere to the recommended laboratory monitoring and management guidelines. Patients or their caregivers should be apprised of the signs and symptoms of glomerulonephritis and to seek medical attention if they occur, including edema, shortness of breath, coughing, hematuria, and decreased urination.

References
1	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2	Product Information. Tegsedi (inotersen). Akcea Therapeutics, Cambridge, MA.