Does Cefepime increase the QTc (QT corrected) interval?

Cefepime and QTc Interval Prolongation

Cefepime does not have a clinically significant effect on QTc interval prolongation based on available evidence. 1

Evidence Assessment

• A clinical study specifically investigating cefepime's effect on QTc interval showed no significant QTc prolongation in ICU patients, with the QTc interval actually shortening by 2-3 ms during or after infusion (p>0.65) 1
• No observational or cohort studies have demonstrated that cefepime has a QT-prolonging effect or increases the risk of Torsade de Pointes (TdP) 1
• Unlike other medications such as ciprofloxacin, which is explicitly mentioned in guidelines as having QT-prolonging potential, cefepime is not listed among medications known to prolong QTc interval in major guidelines 2

QTc Prolongation Risk Assessment

Medications Known to Prolong QTc

• Guidelines from the British Thoracic Society specifically list medications with QT-prolonging potential, including:

  • Antiarrhythmics (amiodarone, sotalol, procainamide, disopyramide, quinidine) 2
  • Antiemetics (domperidone, metoclopramide, 5HT3 antagonists) 2
  • Antipsychotics (thioridazine, haloperidol, chlorpromazine, etc.) 2
  • Antimalarials (chloroquine, hydroxychloroquine) 2
  • Fluoroquinolones (as a class) 2
  • Macrolide antibiotics 3
  • Bedaquiline 2

• Cefepime (a fourth-generation cephalosporin antibiotic) is notably absent from these lists of QT-prolonging medications 2

Clinical Significance of QTc Prolongation

• QTc prolongation increases the risk of TdP, a potentially life-threatening ventricular arrhythmia 4, 5
• For every 10 ms increase in QTc interval, there is approximately a 5% increase in the risk of arrhythmic events 4
• Normal QTc intervals are typically <450 ms for men and <460 ms for women 2
• QTc values from 440-470 ms are considered a "grey zone" due to overlap between affected and unaffected individuals 2

Monitoring Recommendations

When to Monitor QTc

• ECG monitoring is recommended before initiation and during treatment with medications known to prolong QTc interval 2
• Since cefepime is not recognized as a QTc-prolonging medication, routine ECG monitoring specifically for QTc prolongation is not required when using cefepime alone 1
• However, ECG monitoring may be warranted if cefepime is used in patients with:
  • Pre-existing QTc prolongation 2
  • Multiple risk factors for QTc prolongation 5
  • Concomitant use of other QTc-prolonging medications 2

Risk Factors for QTc Prolongation

• Patient-specific risk factors include:
  • Female sex (16.30 ms longer QTc compared to men) 6
  • Age >65 years 4, 6
  • Electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia) 5, 6
  • Heart failure 5
  • Bradycardia 5
  • Genetic predisposition 5
  • Use of loop diuretics 6

Management Considerations

• If a patient requires cefepime and has risk factors for QTc prolongation:

  • Correct electrolyte abnormalities (particularly potassium and magnesium) 2, 5
  • Avoid concurrent use of multiple QTc-prolonging medications when possible 2
  • Consider baseline ECG if patient has multiple risk factors 2

• If QTc interval reaches >500 ms or increases by >60 ms from baseline while on any medication:

  • Consider dose reduction or discontinuation of any QTc-prolonging medications 2
  • Correct electrolyte abnormalities 2, 5
  • Consider continuous ECG monitoring until QTc normalizes 5

Clinical Pitfalls and Caveats

• While cefepime itself does not significantly prolong QTc, patients receiving it may have other risk factors or medications that do 5, 6
• ICU patients are particularly vulnerable to QTc prolongation due to multiple risk factors and polypharmacy 7
• Always consider the entire medication regimen when assessing QTc prolongation risk, not just individual medications 6
• QTc prolongation risk increases substantially with multiple QTc-prolonging medications (11.08 ms with one QT-prolonging drug, additional 3.04 ms with a second QT-prolonging drug) 6