Safety of Augmentin (Amoxicillin/Clavulanate) with Tikosyn (Dofetilide)
Augmentin (amoxicillin/clavulanate) should not be used with Tikosyn (dofetilide) due to the significant risk of QT prolongation and potentially fatal torsades de pointes. 1
Mechanism of Interaction
Dofetilide is a Class III antiarrhythmic medication that works by selectively blocking the rapid component of the delayed rectifier potassium current (IKr), which prolongs the QT interval and increases the effective refractory period of cardiac myocytes 2. This mechanism makes it effective for treating atrial fibrillation and atrial flutter, but also creates an inherent risk of QT prolongation and torsades de pointes.
While amoxicillin alone does not typically cause QT prolongation, the clavulanate component in Augmentin has chemical similarities to trimethoprim, which is explicitly contraindicated with dofetilide 1, 2. The American Heart Association and American College of Cardiology specifically list trimethoprim-containing medications as contraindicated with dofetilide due to the risk of QT interval prolongation 1.
Specific Risks
The combination presents several specific risks:
- QT Prolongation: The risk of QT prolongation is significantly increased when dofetilide is combined with medications that have similar effects or that interfere with its metabolism 3
- Torsades de Pointes: This potentially fatal ventricular arrhythmia is the most serious consequence of QT prolongation 3
- Pharmacokinetic Interaction: Some antibiotics can inhibit the metabolism of dofetilide, leading to increased plasma levels and enhanced QT-prolonging effects 2
Alternative Antibiotic Options
If antibiotic therapy is necessary for a patient on dofetilide, consider these safer alternatives:
For respiratory infections: Consider macrolides with lower QT-prolonging potential (though still use with caution) or non-macrolide antibiotics that don't affect QT interval 1
For skin infections: Consider cephalosporins with minimal QT effects
For urinary tract infections: Consider nitrofurantoin or fosfomycin (if appropriate for the infection) 4
Required Monitoring if Combination Cannot Be Avoided
In rare situations where the combination cannot be avoided:
- Obtain baseline ECG before starting the antibiotic
- Monitor ECG 2-4 hours after administration of the first few doses
- Check electrolytes (especially potassium and magnesium) and correct if abnormal
- Discontinue if QT interval exceeds 500 ms or increases by >60 ms from baseline
- Consider hospitalization for high-risk patients starting both medications simultaneously 1
Risk Factors for QT Prolongation
Patients with the following characteristics are at particularly high risk if exposed to this drug combination:
- Female gender
- Advanced age
- Hypokalemia or hypomagnesemia
- Bradycardia
- Congestive heart failure
- Renal dysfunction
- Baseline QT prolongation
- Concomitant use of other QT-prolonging medications 1
Conclusion
Given the significant risks and the availability of safer antibiotic alternatives, Augmentin should not be used concurrently with dofetilide. The potential for QT prolongation and torsades de pointes represents a serious risk to patient safety that outweighs the benefits of using this specific antibiotic combination.