What are the interactions with Dofetilide (Tikosyn)?

From the Guidelines

Tikosyn (dofetilide) should be used with caution due to its potential to cause Torsades de Pointes, and its use should be carefully monitored, especially when combined with other medications that prolong the QT interval or inhibit CYP3A4 enzymes, as recommended by the 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia 1. When considering the use of Tikosyn, it is essential to be aware of its potential interactions with other medications.

• Medications that prolong the QT interval, such as certain antibiotics (clarithromycin, erythromycin), antifungals (ketoconazole, itraconazole), antipsychotics (thioridazine), and antidepressants (citalopram), should be avoided due to the increased risk of Torsades de Pointes.
• Diuretics that lower potassium levels should also be used cautiously with Tikosyn, as low potassium can increase arrhythmia risk.
• Verapamil, cimetidine, trimethoprim, prochlorperazine, and megestrol can increase Tikosyn levels and should be avoided. The risk of Torsades de Pointes with Tikosyn is also influenced by factors such as renal dysfunction, hypokalemia, and concomitant use of other QT-prolonging drugs, as highlighted in the 2010 scientific statement from the American Heart Association and the American College of Cardiology Foundation on the prevention of Torsades de Pointes in hospital settings 1. It is crucial to carefully evaluate the risk-benefit analysis in individual patients and consider alternative medications when possible.
• The use of Tikosyn requires careful dosing based on kidney function and should only be initiated in a hospital setting with continuous cardiac monitoring for at least three days.
• Before starting Tikosyn, patients should inform their healthcare provider about all medications they take, including over-the-counter drugs and supplements. By being aware of these potential interactions and taking necessary precautions, healthcare providers can minimize the risk of adverse events associated with Tikosyn use.

From the FDA Drug Label

The concomitant use of verapamil or the cation transport system inhibitors cimetidine, trimethoprim (alone or in combination with sulfamethoxazole), or ketoconazole with TIKOSYN is contraindicated (see WARNINGS and PRECAUTIONS, Drug-Drug Interactions), as each of these drugs cause a substantial increase in dofetilide plasma concentrations In addition, other known inhibitors of the renal cation transport system such as prochlorperazine, dolutegravir and megestrol should not be used in patients on TIKOSYN The concomitant use of hydrochlorothiazide (alone or in combinations such as with triamterene) with TIKOSYN is contraindicated (see PRECAUTIONS, Drug-Drug Interactions) because this has been shown to significantly increase dofetilide plasma concentrations and QT interval prolongation. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with TIKOSYN (500 mcg BID) for 7 days has been shown to increase dofetilide plasma levels by 58% Verapamil Concomitant use of verapamil is contraindicated Co-administration of TIKOSYN with verapamil resulted in increases in dofetilide peak plasma levels of 42%, although overall exposure to dofetilide was not significantly increased. Ketoconazole at 400 mg daily (the maximum approved prescription dose) co-administered with TIKOSYN (500 mcg BID) for 7 days has been shown to increase dofetilide Cmax by 53% in males and 97% in females, and AUC by 41% in males and 69% in females Trimethoprim Alone or in Combination with Sulfamethoxazole (see WARNINGS, CONTRAINDICATIONS) Concomitant use of trimethoprim alone or in combination with sulfamethoxazole is contraindicated. Hydrochlorothiazide (HCTZ) Alone or in Combination with Triamterene (see CONTRAINDICATIONS) Concomitant use of HCTZ alone or in combination with triamterene is contraindicated.

Tikosyn Interactions:

• Contraindicated interactions:
  • Verapamil
  • Cimetidine
  • Trimethoprim (alone or in combination with sulfamethoxazole)
  • Ketoconazole
  • Hydrochlorothiazide (alone or in combination with triamterene)
  • Prochlorperazine
  • Dolutegravir
  • Megestrol
• Increased risk of Torsade de Pointes:
  • Digoxin
  • Verapamil 2 2

From the Research

Tikosyn Interactions

• Dofetilide, also known as Tikosyn, is a class III antiarrhythmic drug that has been approved for the treatment of atrial fibrillation 3, 4, 5, 6, 7.
• The drug works by selectively blocking a specific cardiac potassium channel, increasing the effective refractory period of the myocyte and thereby terminating reentrant arrhythmias 5.
• Tikosyn interactions include:
  • Concomitant use of drugs that increase the plasma level of dofetilide is contraindicated, such as cimetidine, ketoconazole, trimethoprim-sulfamethoxazole, and verapamil 5.
  • Dofetilide can be co-administered with digoxin and beta-blockers 6.
  • Other anti-arrhythmic drugs, as well as drugs that interfere with the renal elimination or the metabolism of dofetilide, must be avoided 6.
• Caution must be used when initiating dofetilide therapy to avoid torsade de pointes ventricular tachycardia, especially in patients with heart failure, hypertrophy, bradycardia, and female gender 3, 7.
• Therapy should be initiated in hospital under electrocardiogram monitoring for at least two to three days, with particular care to avoid torsade de pointes in high-risk patients 5, 7.