Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIV0CNHSD)
Drug Name			Sumatriptan		Drug Info		Ondansetron		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Vasoconstrictor Agents				Antiemetics
Structure

Mechanism of Sumatriptan-Ondansetron Interaction (Severity Level: Major)
Additive serotonergic effects Click to Show/Hide Mechanism Graph

Drug Name		Sumatriptan				Ondansetron
Mechanism		Serotonergic effects 5-HT 1 receptor Agonist				Serotonergic effects 5-HT 3 receptor Antagonist
Key Mechanism Factor 1
		Factor Name		5-HT 1 receptor				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		5-HT 3 receptor				Structure Sequence
		Protein Family		Ligand-gated ion channel (TC 1.A.9) family
		Protein Function		This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel. Click to Show/Hide
Mechanism Description		Additive serotonergic effects by the combination of Sumatriptan and Ondansetron

Recommended Action
Management		Caution is advised if 5-HT3 receptor antagonists are prescribed with other agents that affect the serotonergic neurotransmitter system. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is warranted when initiating or increasing the dosages of these agents. The potential risk for serotonin syndrome should be considered even when administering serotonergic agents sequentially, as some agents may demonstrate a prolonged elimination half-life. For example, a 5-week washout period is typically recommended following use of fluoxetine and 2 weeks following use of MAOIs before administering another serotonergic agent. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary.

References
1	Canadian Pharmacists Association.
2	Cerner Multum, Inc. "Australian Product Information.".
3	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4	Product Information. Akynzeo (netupitant-palonosetron). Eisai Inc, Woodcliff Lake, NJ.
5	Product Information. Aloxi (palonosetron). MGI Pharma Inc, Minnetonka, MN.
6	Product Information. Anzemet (dolasetron). Hoechst Marion-Roussel Inc, Kansas City, MO.
7	Product Information. Sancuso (granisetron). ProStrakan Group, Bedminster, NJ.