Is it safe to take Cipro (ciprofloxacin) with Tikosyn (dofetilide)?

Ciprofloxacin Should Not Be Taken with Tikosyn Due to Serious Risk of QT Prolongation and Torsades de Pointes

Ciprofloxacin and Tikosyn (dofetilide) should not be used together due to the high risk of QT interval prolongation and potentially fatal cardiac arrhythmias. 1

Mechanism of Interaction

The combination of ciprofloxacin and dofetilide creates a dangerous situation through multiple mechanisms:

1. Direct QT prolongation effects: Both medications independently prolong the QT interval

   • Dofetilide is a class III antiarrhythmic that selectively blocks cardiac potassium channels (IKr), increasing the refractory period 2
   • Ciprofloxacin can also cause QT prolongation, though traditionally considered less risky than other fluoroquinolones 3

2. Pharmacokinetic interaction: Ciprofloxacin inhibits the metabolism of dofetilide

   • This leads to increased dofetilide plasma concentrations and enhanced QT-prolonging effects

Evidence Supporting This Contraindication

The 2019 AGS Beers Criteria specifically identifies ciprofloxacin as a medication that should be avoided in certain drug combinations due to risk of QT prolongation 1. The British Thoracic Society guidelines also warn about ciprofloxacin's potential for QT prolongation, especially when combined with other QT-prolonging drugs 1.

Case reports document serious adverse events when ciprofloxacin is combined with other QT-prolonging medications:

• Two patients on antiarrhythmic therapy developed marked QTc prolongation (590-680ms) and torsades de pointes requiring defibrillation within 24 hours of starting ciprofloxacin 3

Risk Factors That Increase Danger

The risk of this interaction is heightened by:

• Pre-existing QT prolongation
• Electrolyte disturbances (especially hypokalemia)
• Heart failure
• Renal dysfunction (dofetilide requires dose adjustment based on creatinine clearance) 4
• Acute ischemia (can dramatically increase dofetilide's proarrhythmic effects) 5
• Advanced age
• Female gender

Alternative Approaches

If an antibiotic is needed for a patient on dofetilide:

1. Consider non-fluoroquinolone antibiotics that don't significantly affect QT interval or interact with dofetilide
2. Consult with cardiology and infectious disease specialists to determine the safest alternative antibiotic based on the specific infection
3. If no alternatives exist and the combination must be used (extremely rare circumstance), consider:
   • Temporary discontinuation of dofetilide if clinically appropriate
   • Intensive cardiac monitoring in a hospital setting
   • Frequent ECG monitoring and electrolyte checks

Monitoring Requirements If Unavoidable

If this combination absolutely cannot be avoided (which would be extremely rare):

• Hospitalize the patient for continuous cardiac monitoring
• Obtain baseline ECG and electrolytes
• Monitor ECG at 2-4 hours after each dose
• Discontinue both medications if QTc exceeds 500ms or increases by >60ms from baseline
• Maintain potassium and magnesium at high-normal levels
• Have emergency resuscitation equipment readily available

Bottom Line

The combination of ciprofloxacin and dofetilide (Tikosyn) should be avoided due to the significant risk of QT prolongation and life-threatening arrhythmias. Alternative antibiotics should be selected for patients taking dofetilide. 1