Drug General Information (ID: DDIVCI56GL)
Drug Name			Dofetilide		Drug Info		Hydrochlorothiazide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antiarrhythmic Agents				Diuretics
Structure

Mechanism of Dofetilide-Hydrochlorothiazide Interaction (Severity Level: Major)
Decreased metabolism (Unspecific) Click to Show/Hide Mechanism Graph
Drug Name		Dofetilide				Hydrochlorothiazide
Mechanism 1		Dofetilide				Increase the plasma concentrations of dofetilide
Key Mechanism Factor 1
		Factor Name		Pharmacokinetics
		Factor Description		Alters the metabolism of the drug, leading to changes in the plasma concentration of the drug and affecting the pharmacological effects.
Mechanism Description		Decreased metabolism of Dofetilide caused by Hydrochlorothiazide
Increased risk of ventricular arrhythmias Click to Show/Hide Mechanism Graph
Drug Name		Dofetilide				Hydrochlorothiazide
Mechanism 2		Prolong QT interval				Hypokalemia
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 Dofetilide and Hydrochlorothiazide

Recommended Action
Management		Because QT interval prolongation may be associated with serious ventricular arrhythmias such as torsade de pointes tachycardia, use of dofetilide in combination with hydrochlorothiazide is considered contraindicated.

References
1	Product Information. Tikosyn (dofetilide) Pfizer US Pharmaceuticals, Atlanta, GA.
2	Tapaninen T, Neuvonen PJ, Niemi M "Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren." Clin Pharmacol Ther 88 (2010): 339-42. [PMID: 20664534]
3	Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP "Clinical pharmacokinetics and pharmacodynamics of aliskiren." Clin Pharmacokinet 47 (2008): 515-31. [PMID: 18611061]