In a patient with an acute upper gastrointestinal bleed who is taking levetiracetam, should the levetiracetam be discontinued?

Levetiracetam Does NOT Need to Be Discontinued for Upper Gastrointestinal Bleeding

Levetiracetam should be continued during an acute upper gastrointestinal bleed—there is no evidence-based reason to discontinue this antiepileptic medication, and doing so creates unnecessary seizure risk without any bleeding benefit. 1

Why Levetiracetam Can Be Safely Continued

Absorption Profile Supports Continuation

• Levetiracetam demonstrates site-independent absorption throughout the entire gastrointestinal tract, including the proximal small bowel (98.5% bioavailability), distal small bowel (100.8% bioavailability), and ascending colon (87.1% bioavailability) compared to oral tablet administration 1
• The drug maintains comparable systemic bioavailability regardless of which GI segment is functioning, meaning that even with upper GI bleeding, absorption from lower segments remains adequate 1
• This pharmacokinetic profile makes levetiracetam uniquely suitable for continuation during GI bleeding episodes 1

No Bleeding Risk from Levetiracetam

• Levetiracetam is not an antiplatelet agent, anticoagulant, or NSAID—it has no mechanism that would increase bleeding risk 1
• The drug binds to synaptic vesicle protein SV2A and has no effect on coagulation pathways or platelet function 1
• Unlike medications that genuinely require assessment during GI bleeding (aspirin, clopidogrel, warfarin, DOACs, NSAIDs), levetiracetam poses no hemostatic concerns 2, 3

Critical Management Priorities During Upper GI Bleeding

Medications That Actually Require Decision-Making

The focus during acute upper GI bleeding should be on medications that genuinely affect bleeding risk:

Antiplatelet agents:

• For aspirin used in secondary prevention, temporarily withhold only during active serious bleeding, then restart as soon as hemostasis is achieved 3
• For dual antiplatelet therapy, never discontinue both agents simultaneously due to stent thrombosis risk; continue aspirin and temporarily withhold the P2Y12 inhibitor 3
• Resume P2Y12 inhibitors within 5 days after endoscopic hemostasis 3

Anticoagulants:

• Direct oral anticoagulants should be interrupted at presentation with upper GI bleeding 3
• Consider restarting DOACs within a maximum of 7 days after bleeding has stopped 3

Standard Upper GI Bleeding Management

• Initiate high-dose proton pump inhibitor therapy for all patients 3, 4, 5
• Perform endoscopy within 24 hours after appropriate resuscitation 6, 5
• Provide intravenous fluid resuscitation and red cell transfusion at hemoglobin threshold of 70-80 g/L 5

Common Pitfall to Avoid

Do not reflexively discontinue all medications during GI bleeding. The critical error is stopping medications like levetiracetam that have no bleeding mechanism, which exposes the patient to preventable seizure risk without any hemostatic benefit. Only medications with direct effects on coagulation, platelet function, or gastric mucosal integrity (anticoagulants, antiplatelets, NSAIDs) require consideration for temporary discontinuation 2, 3, 6.

Practical Algorithm

1. Continue levetiracetam at current dose throughout the bleeding episode and hospitalization 1
2. Assess and manage medications that actually affect bleeding: antiplatelets, anticoagulants, NSAIDs 2, 3
3. Initiate standard upper GI bleeding management: high-dose PPI, resuscitation, early endoscopy 3, 4, 5
4. Maintain seizure prophylaxis by ensuring levetiracetam administration continues, even if patient is NPO (can be given IV if needed) 1