Drug General Information (ID: DDIUXWYD14)
Drug Name			Arsenic trioxide		Drug Info		Clomipramine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antineoplastics				Antidepressants
Structure

Mechanism of Arsenic trioxide-Clomipramine Interaction (Severity Level: Major)
Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Drug Name		Arsenic trioxide				Clomipramine
Mechanism 1		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 Arsenic trioxide and Clomipramine
Increased risk of ventricular arrhythmias Click to Show/Hide Mechanism Graph
Drug Name		Arsenic trioxide				Clomipramine
Mechanism 2		Delay atrioventricular conduction				Prolong QT interval
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 Arsenic trioxide and Clomipramine

Recommended Action
Management		If possible, medications that are known to prolong the QT interval should be discontinued prior to initiating therapy with arsenic trioxide and withheld for at least several weeks after completion of therapy. Caution is advised if concomitant use cannot be avoided. Patients should have frequent ECGs and be monitored for arrhythmias when QT interval is prolonged. An absolute QT interval exceeding 500 msec will require immediate action to correct concomitant risk factors, if any, as well as a thorough assessment of the need for continued therapy. Patients who develop syncope or arrhythmia should be hospitalized for clinical and laboratory monitoring.

References
1	Ohnishi K, Yoshida H, Shigeno K, et al. "Prolongation of the QT interval and ventricular tachycardia in patients treated with arsenic trioxide for acute promyelocytic leukemia." Ann Intern Med 133 (2000): 881-5. [PMID: 11103058]
2	Product Information. Trisenox (arsenic trioxide) Cephalon Inc, West Chester, PA.