How should levetiracetam (Keppra) be administered to a patient with a percutaneous endoscopic gastrostomy (PEG) tube?

Administration of Levetiracetam (Keppra) via PEG Tube

Crush the levetiracetam tablet, dissolve it in water or saline, and administer it through the PEG tube followed by a 40 mL water flush—this method maintains bioavailability comparable to intact tablets and is safe for patients requiring enteral administration. 1, 2, 3

Preparation and Administration Technique

Tablet Preparation

• Crush the immediate-release levetiracetam tablet and dissolve it in water or saline before administration through the PEG tube 2, 3
• The crushed formulation demonstrates pharmacokinetics comparable to intact tablets, with no significant impairment in rate or extent of absorption 3
• Avoid using the extended-release (XR) formulation via PEG tube, as crushing destroys the extended-release mechanism 4

Flushing Protocol

• Flush the PEG tube with 40 mL of water immediately before medication administration 1
• Flush again with 40 mL of water immediately after medication administration to prevent tube clogging 5, 1
• This flushing protocol is critical because inadequate flushing is a primary cause of tube blockage 1

Administration Method

• Administer the dissolved medication via appropriate ENFit syringe with ISO 80369-3 standard connectors to prevent fatal misconnection errors 1
• The medication can be given through either oral or nasogastric/orogastric routes with equivalent absorption 2
• Maintain head of bed elevation at 30-45 degrees during and for 1-2 hours after administration to reduce aspiration risk 1

Dosing Considerations

Loading Doses

• For patients requiring rapid therapeutic levels, a 1,500 mg oral load can be administered via PEG tube 5
• Studies demonstrate no seizures within 24 hours of oral loading in appropriate patients 5
• Rapid IV loading is also safe and well tolerated in doses up to 60 mg/kg, though this requires IV access 5

Maintenance Dosing

• Standard maintenance doses can be administered via crushed tablets through the PEG tube 2, 3
• Pharmacokinetic studies in neonates receiving crushed tablets via nasogastric tube showed therapeutic drug levels were achieved and maintained 2

Bioavailability and Absorption

Gastrointestinal Absorption Profile

• Levetiracetam demonstrates site-independent absorption throughout the GI tract 6
• Bioavailability from the proximal small bowel (98.5%), distal small bowel (100.8%), and ascending colon (87.1%) is comparable to oral tablet administration 6
• This broad absorption profile makes levetiracetam particularly suitable for PEG tube administration 6

Effect of Mixing with Enteral Formulas

• Mixing crushed levetiracetam with enteral nutrition formulas does not significantly impair overall absorption 3
• Peak serum concentrations may be slightly reduced when mixed with enteral formulas (10.8 μg/mL vs 14.8 μg/mL for intact tablet), but this difference is not clinically significant 3
• Mean serum concentrations at 12 hours post-dose remain similar regardless of administration method (approximately 4 μg/mL) 3

Safety Profile

Common Adverse Effects

• The most common adverse effects are somnolence, asthenia, dizziness, fatigue, and irritability 5, 7
• These effects typically appear early after initiation and generally resolve without medication withdrawal 7
• Behavioral adverse effects are more common in children and patients with prior behavioral problems 7

PEG Tube-Specific Precautions

• PEG tubes do not eliminate aspiration risk—aspiration pneumonia remains a significant concern with a hazard ratio of 2.2 for mortality 1
• Verify the tube is properly positioned before each medication administration 8
• Monitor the stoma site for signs of infection, leakage, or buried bumper syndrome, particularly during the first week after placement 5, 9

Troubleshooting Tube Blockage

Prevention

• Consistent flushing with 40 mL water before and after each medication is the primary prevention strategy 5, 1
• Ensure complete dissolution of the crushed tablet before administration 2, 3

Management of Blockage

• First-line: Flush with 40-60 mL of warm water using gentle pressure 1
• Second-line: Use alkaline pancreatic enzyme solution (96% success rate for formula-related clogs) 1
• Avoid carbonated drinks, pineapple juice, or sodium bicarbonate as these degrade the tube 1
• Never use excessive force, which may rupture the tube 1

Clinical Efficacy via PEG Tube

• Studies in neonates receiving crushed levetiracetam via nasogastric tube demonstrated seizure termination in 90% by day 3 and 100% by day 4 post-initiation 2
• The pharmacokinetic profile of crushed tablets administered enterally supports therapeutic efficacy comparable to intact oral formulations 2, 3

Important Caveats

• Involve a pharmacist when planning medication administration through PEG tubes, as over 30% of caregivers receive no information about this practice 1
• Liquid formulations are generally preferred over crushed tablets when available, though levetiracetam tablets crush well and maintain bioavailability 1, 3
• Document the off-label nature of crushing tablets, as this represents use outside the licensed indication 1
• The extended-release formulation should never be crushed, as this destroys the controlled-release mechanism 4