Do diltiazem and verapamil interact with dofetilide?

Diltiazem and Verapamil Are Contraindicated with Dofetilide

Yes, both diltiazem and verapamil are contraindicated with dofetilide due to significant drug interactions that increase the risk of life-threatening arrhythmias. 1

Mechanism of Interaction

The interaction between these medications occurs through multiple mechanisms:

1. Pharmacokinetic interaction:

   • Verapamil is explicitly contraindicated with dofetilide according to the FDA label 1
   • Verapamil increases dofetilide peak plasma levels by 42% 1, 2
   • Diltiazem inhibits CYP3A4, which can increase systemic dofetilide exposure 1

2. Pharmacodynamic effects:

   • Both drugs can prolong QT interval
   • The combination increases risk of Torsade de Pointes 1, 2

Evidence from Drug Labeling

The FDA label for dofetilide (Tikosyn) explicitly states:

• "The concomitant use of verapamil with TIKOSYN is contraindicated" 1
• "Inhibitors of the CYP3A4 isoenzyme (including diltiazem) should be cautiously co-administered with TIKOSYN as they can potentially increase dofetilide levels" 1

Clinical Implications

When verapamil is combined with dofetilide:

• Peak plasma concentration of dofetilide increases by 43% 2
• AUC increases by 26% 2
• QT interval prolongation increases from 20 msec (dofetilide alone) to 26 msec (combination) 2

These changes significantly increase the risk of Torsade de Pointes, a potentially fatal ventricular arrhythmia.

Alternative Management Options

For patients requiring rate control who are on dofetilide:

1. Beta-blockers may be considered as alternatives, though they should be used with caution and with appropriate monitoring for bradycardia 3

2. Amlodipine has no significant interaction with dofetilide and may be considered if a calcium channel blocker is needed 1

3. Catheter ablation should be considered for definitive treatment of SVT in patients with recurrent episodes, especially when medication options are limited 4

Monitoring Recommendations

If a patient is inadvertently given this combination:

• Immediate ECG monitoring for QT prolongation
• Watch for signs of Torsade de Pointes
• Monitor for bradycardia and hypotension
• Consider discontinuation of one of the agents

Important Caveats

• The risk is particularly high in patients with renal dysfunction, electrolyte abnormalities, or structural heart disease 1
• Elderly patients and those with hepatic impairment may be at higher risk 4
• The interaction may be more pronounced during the first few hours after dosing when peak plasma concentrations occur 2

This contraindication is based on clear evidence of increased risk without compensatory benefit, making this a firm recommendation to avoid combining these medications.