What is the recommended route of administration for seizure medications?

Routes of Administration for Seizure Medications

For patients with seizure disorders, the route of administration should be selected based on clinical context, with intravenous (IV) routes preferred for emergency situations like status epilepticus, while oral routes are appropriate for maintenance therapy when the patient is stable. 1

Emergency Seizure Management

Status Epilepticus

• IV administration is the preferred route for treating status epilepticus due to rapid onset of action and complete bioavailability 1
• Level A recommendation: Emergency physicians should administer an additional antiepileptic medication in ED patients with refractory status epilepticus who have failed treatment with benzodiazepines 1
• Level B recommendation: IV phenytoin, fosphenytoin, or valproate are recommended for refractory status epilepticus after benzodiazepine failure 1
• Level C recommendation: IV levetiracetam, propofol, or barbiturates may be administered in patients with refractory status epilepticus who have failed benzodiazepine treatment 1

When IV Access is Not Available

• Intramuscular (IM) midazolam has been shown to be superior to IV lorazepam in prehospital settings for status epilepticus (73.4% vs 63.4% seizure cessation rate) 2
• Rectal diazepam is FDA-approved for out-of-hospital treatment of acute seizures 3
• Buccal or intranasal midazolam are recommended alternatives when IV access is not available 3, 4

Specific Medication Routes and Considerations

Benzodiazepines

• First-line treatment for status epilepticus with multiple available routes 5, 4
• Lorazepam and midazolam: Available for IV, IM, buccal, sublingual, or intranasal administration 3
• Diazepam: Available for IV, rectal administration (only FDA-approved rectal formulation in US) 3, 2
• Caution: Benzodiazepines may cause hypotension and respiratory depression 6

Phenytoin/Fosphenytoin

• Phenytoin: IV administration at maximum rate of 50 mg/min; oral loading also possible but takes >5 hours to reach therapeutic levels 1
• Fosphenytoin: IV or IM administration possible at maximum rate of 150 PE/min 1
• Phenytoin should NOT be given intramuscularly despite having a parenteral preparation 2, 6
• IV phenytoin requires a filter and infusion pump 1
• Caution: IV phenytoin associated with cardiac arrhythmias, hypotension, and tissue injury at injection site 6

Valproate

• IV administration up to 30 mg/kg at maximum rate of 10 mg/kg/min 1
• Should NOT be given intramuscularly despite having a parenteral preparation 2
• Fewer adverse events compared to IV phenytoin 1

Levetiracetam

• Oral loading: 1,500 mg; IV loading: up to 60 mg/kg 1
• Both oral and IV routes well-tolerated with minimal side effects 1

Phenobarbital

• IV administration for status epilepticus: 15-20 mg/kg over 10-15 minutes 1, 7
• Adult IV dosing should not exceed 60 mg/min 7
• IM administration should be deep into a large muscle, not exceeding 5 mL at any one site 7
• Caution: Subcutaneous administration is not recommended 7

Clinical Decision-Making

• For patients with known seizure disorders in the ED setting requiring medication resumption, there is insufficient evidence to support one route (oral vs parenteral) over another for preventing early recurrent seizure 1
• The choice of administration route should be based on clinical context and physician discretion 1
• For stable patients, oral administration is preferred due to:
  • Lower cost 1
  • Fewer serious adverse effects 1
  • Patient comfort and convenience 3
• For emergency situations, IV administration is preferred due to:
  • Faster achievement of therapeutic levels 1
  • Complete bioavailability 6
  • Ability to control administration rate 6

Important Considerations and Pitfalls

• Intravenous injection should be slow and careful with monitoring of vital signs to prevent adverse effects 7
• Avoid small veins (e.g., dorsum of hand/wrist) for IV administration to minimize irritation and thrombosis risk 7
• Inadvertent intraarterial injection can cause severe consequences ranging from pain to gangrene 7
• When IV access is not available or difficult to obtain, consider alternative routes such as IM, rectal, buccal, or intranasal depending on the medication 3, 2, 4
• Some medications have poor rectal bioavailability (gabapentin, oxcarbazepine, phenytoin) and should not be administered by this route 2