Do cefepime and Ranexa (ranolazine) interact?

Cefepime and Ranolazine Interaction

Cefepime and ranolazine do not have a clinically significant direct drug-drug interaction, but caution should be exercised when using cefepime in patients taking ranolazine due to cefepime's neurotoxicity risk profile. 1

Mechanism and Evidence Assessment

The American Heart Association's scientific statement on drug-drug interactions with statins and cardiovascular agents does not identify any direct interaction between cefepime and ranolazine 1. While ranolazine is known to be a CYP3A4 inhibitor and P-glycoprotein inhibitor, cefepime is primarily eliminated unchanged through renal excretion rather than hepatic metabolism 2.

Key considerations:

• Cefepime is eliminated primarily via renal excretion with over 80% recovered unchanged in urine 2
• Ranolazine is metabolized by CYP3A4 and is a moderate inhibitor of CYP3A4 and P-glycoprotein 1
• No specific interactions between these two medications have been reported in clinical guidelines or research

Clinical Implications

While there is no direct pharmacokinetic interaction, clinicians should be aware of potential additive adverse effects:

1. Neurotoxicity risk: Cefepime has been associated with neurotoxicity, including:

   • Non-convulsive status epilepticus 3, 4
   • Encephalopathy 5
   • Altered mental status 6

2. QT interval considerations: Ranolazine may cause QT prolongation, and while cefepime is not known to significantly affect QT interval, monitoring may be prudent in patients with other risk factors for QT prolongation 1

Risk Factors for Adverse Effects

When using these medications together, be particularly vigilant in patients with:

• Renal dysfunction: Cefepime neurotoxicity risk increases significantly with impaired renal function 6, 5
• Advanced age: Elderly patients are more susceptible to cefepime neurotoxicity even with normal renal function 3
• Liver disease: Hepatic dysfunction may increase blood-brain barrier permeability, potentially increasing cefepime neurotoxicity risk 5

Recommendations for Clinical Practice

1. Assess renal function before initiating cefepime in patients on ranolazine
2. Consider dose adjustment of cefepime in patients with renal impairment according to guidelines 7
3. Monitor for neurological symptoms including altered mental status, confusion, or seizure-like activity
4. Discontinue cefepime if unexplained neurological manifestations occur 1
5. Consider EEG monitoring in patients who develop altered mental status while receiving both medications

Conclusion

While there is no established direct pharmacokinetic interaction between cefepime and ranolazine, clinicians should remain vigilant for potential neurotoxicity, especially in high-risk patients. The combination can be used when clinically indicated with appropriate monitoring and dose adjustments based on renal function.