Cephalexin and Tikosyn (Dofetilide) Interaction
Cephalexin should NOT be used concurrently with Tikosyn (dofetilide) due to the risk of serious cardiac arrhythmias.
Contraindication Rationale
Tikosyn (dofetilide) has specific contraindications with certain medications that can increase plasma levels or prolong the QT interval, potentially leading to life-threatening arrhythmias:
- According to the American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines, verapamil is explicitly contraindicated with dofetilide due to drug interactions 1.
- While cephalexin is not specifically mentioned in these guidelines, caution must be exercised with any medication that might interact with dofetilide.
Drug Interaction Mechanism
The primary concern with this combination involves:
QT Prolongation Risk: Dofetilide is a class III antiarrhythmic that works by selectively blocking cardiac potassium channels (IKr), which increases the effective refractory period of myocytes 2. This mechanism inherently carries a risk of QT prolongation and torsades de pointes.
Metabolism Considerations: Dofetilide has known contraindications with medications that can increase its plasma levels, including cimetidine, ketoconazole, trimethoprim-sulfamethoxazole, and verapamil 2.
Alternative Antibiotic Options
If antibiotic therapy is necessary for a patient on dofetilide, consider these safer alternatives:
- For skin and soft tissue infections: Clindamycin 300 mg PO four times daily 1
- For respiratory infections: Consider consultation with an infectious disease specialist for appropriate alternatives
Monitoring Requirements
If, despite contraindications, both medications must be used together (which is strongly discouraged):
- Mandatory inpatient cardiac monitoring
- Daily ECG monitoring for QT prolongation
- Serum electrolyte monitoring (particularly potassium and magnesium)
- Immediate discontinuation if QT prolongation occurs
Important Precautions
- Avoid concurrent therapy: The safest approach is to avoid concurrent use of cephalexin with dofetilide.
- Consider drug substitution: If antibiotic therapy is necessary, select an alternative antibiotic with minimal risk of QT prolongation or drug interactions.
- Consult cardiology: Before making any changes to dofetilide therapy, consult with the prescribing cardiologist.
Common Pitfalls to Avoid
- Overlooking the interaction: Failing to recognize the potential for serious cardiac arrhythmias when combining these medications.
- Inadequate monitoring: If concurrent therapy cannot be avoided, insufficient cardiac monitoring could lead to missed early signs of QT prolongation.
- Electrolyte imbalances: Not addressing electrolyte abnormalities that could further increase arrhythmia risk.
The risk of torsades de pointes with dofetilide is dose-dependent and requires careful management. Given the potential for serious cardiac events, the most prudent approach is to select an alternative antibiotic when a patient is taking dofetilide.