Can Keppra (levetiracetam) cause hypotension?

Levetiracetam and Hypotension

Levetiracetam (Keppra) can cause hypotension, particularly when administered intravenously at high doses or rapid rates, though this adverse effect is relatively uncommon.

Evidence for Hypotension with Levetiracetam

Levetiracetam is an established second-generation antiepileptic drug with a unique mechanism of action that involves binding to synaptic vesicle protein 2A and inhibiting calcium release from intraneuronal stores 1. While generally well-tolerated, cardiovascular effects have been documented:

• A 2022 study evaluating the safety of rapid administration of undiluted high-dose intravenous levetiracetam found that 3 out of 107 patients (3.8%) experienced hypotension after receiving 1500mg doses, though these patients were already on vasopressors prior to administration 2.

• A more concerning case report from 2016 documented cardiovascular toxicity including bradycardia and hypotension in a patient who ingested 60-80g of levetiracetam (overdose). The patient's hypotension responded to atropine and intravenous fluids 3.

• Another study comparing intravenous push (IVP) versus intravenous piggyback (IVPB) administration of levetiracetam found hypotension occurred in 5.2% of IVP administrations versus 3.5% of IVPB administrations, though this difference was not statistically significant (p=0.44) 4.

Risk Factors and Monitoring

The risk of hypotension appears to be higher in certain situations:

• High doses: Particularly in overdose situations where serum concentrations can reach 10-40 times therapeutic levels 5
• Rapid IV administration: Though recent studies suggest even undiluted rapid administration may be relatively safe with appropriate monitoring 2, 4
• Pre-existing cardiovascular conditions: Patients already experiencing hemodynamic instability may be more vulnerable

Management of Levetiracetam-Induced Hypotension

If hypotension occurs during levetiracetam administration:

1. Slow or temporarily stop the infusion if administering intravenously
2. Administer IV fluids to restore blood pressure
3. Consider atropine if bradycardia accompanies hypotension 3
4. Monitor vital signs until stabilized
5. Consider vasopressors in severe cases that don't respond to fluids

Clinical Recommendations

• For IV administration: Monitor blood pressure before and during administration, especially with high doses or rapid administration
• For patients with cardiovascular risk factors: Consider slower infusion rates and closer monitoring
• For oral administration: Routine blood pressure monitoring is sufficient as hypotension is less common with oral dosing

Important Caveats

• Hypotension appears to be dose-dependent and more common with IV administration
• The overall incidence of hypotension with levetiracetam is lower compared to many other antiepileptic medications
• Most cases of levetiracetam-associated hypotension resolve with supportive care
• The mechanism may involve muscarinic receptor effects at high concentrations 3

While levetiracetam can cause hypotension, it remains one of the safer antiepileptic medications from a cardiovascular perspective, especially when compared to alternatives like phenytoin which carries a higher risk of cardiovascular adverse effects 6.