Levetiracetam (Keppra) Does Not Prolong QT Interval
Levetiracetam (Keppra) does not cause clinically significant QT interval prolongation and is considered safe from a cardiac repolarization perspective. This conclusion is supported by high-quality evidence from a randomized, placebo-controlled study specifically designed to evaluate levetiracetam's effect on cardiac repolarization 1.
Evidence Supporting Levetiracetam's Cardiac Safety
A rigorous four-way crossover study in healthy subjects demonstrated that:
- Single doses of levetiracetam at both therapeutic (1000 mg) and supratherapeutic (5000 mg) doses did not significantly prolong the QTc interval 1
- The upper bound of the 95% CI for QTc prolongation was only 8.0-8.1 milliseconds, well below the threshold of concern 1
- No statistically significant relationship was found between levetiracetam plasma concentration and QTc interval changes 1
- This contrasted with the positive control (moxifloxacin), which did show significant QTc prolongation 1
QT Prolongation Risk Assessment
When evaluating medications for QT prolongation risk, it's important to understand:
- QT prolongation increases the risk of torsades de pointes (TdP), a potentially fatal ventricular arrhythmia 2, 3
- High-risk features include QTc >500 ms or an increase of >60 ms from baseline 2
- Patient-specific risk factors include:
- Female sex
- Advanced age (>65 years)
- Heart disease or bradyarrhythmias
- Electrolyte abnormalities (particularly hypokalemia and hypomagnesemia)
- Concomitant use of other QT-prolonging medications 2
Medications Known to Prolong QT Interval
Unlike levetiracetam, many commonly used medications do carry QT prolongation risk:
- Class IA antiarrhythmics (quinidine, procainamide, disopyramide)
- Class III antiarrhythmics (amiodarone, sotalol)
- Fluoroquinolones (moxifloxacin, levofloxacin, ciprofloxacin)
- Macrolides (erythromycin, clarithromycin, azithromycin)
- Antipsychotics (thioridazine, haloperidol, chlorpromazine)
- Certain antiemetics (ondansetron)
- Some proton pump inhibitors (particularly pantoprazole and lansoprazole) 2, 4
Clinical Implications for Levetiracetam Use
Levetiracetam's favorable cardiac safety profile makes it:
- A suitable antiepileptic choice for patients with pre-existing QT prolongation
- Safe to use in patients with cardiac comorbidities
- An appropriate option when patients require multiple medications, reducing the risk of drug interactions that could affect cardiac repolarization 5
Monitoring Considerations
Despite levetiracetam's cardiac safety:
- Standard monitoring practices should still be followed for patients on multiple medications
- For patients on levetiracetam plus other medications with QT-prolonging potential, ECG monitoring may be warranted
- Electrolyte levels (particularly potassium and magnesium) should be maintained within normal ranges in high-risk patients 2
Clinical Pitfall to Avoid
A common mistake is assuming all antiepileptic drugs carry similar cardiac risks. Unlike some other antiepileptics that may affect cardiac conduction, levetiracetam has been specifically studied and shown not to prolong the QT interval, making it a safer choice for patients with cardiac risk factors or those taking multiple medications 1.