Franciscan Health Indianapolis

Medication Use Evaluation

Pharmacy and Therapeutics Committee

DATE PRESENTED TO P&T COMMITTEE:

PRESENTED BY: Hannah Klemm, PharmD

TOPIC: Levetiracetam Loading Dose

SAMPLE: Subjects were selected using an EPIC report for patients receiving levetiracetam intravenous for seizures or
status epilepticus in the emergency department from January 2023 through December 2023, at the Franciscan Health
Indianapolis (FHI) campus.

CRITERIA: Patients who were managed with a levetiracetam due to an active seizure or witnessed seizure by EMS
personnel or hospital staff were assessed for a correct loading dose of levetiracetam and if guideline recommended
therapy was received.

REFERENCES:
1. Levetiracetam. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. March 1, 2024. Accessed March 4, 2024.
http://online.lexi.com
2. Glauser T, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults:
Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016 Jan-Feb;16(1):48-61.
doi: 10.5698/1535-7597-16.1.48.
3. Braun K, et al. Suboptimal Dosing of Benzodiazepines and Levetiracetam in a Cohort of Status Epilepticus
Patients and Outcomes Associated with Inadequate Dosing. J Pharm Pract. 2023 Oct;36(5):1068-1071. doi:
10.1177/08971900221088804. Epub 2022 Apr 10.
4. Parsons A, et al. Treatment of Status Epilepticus: What Are the Guidelines and Are We Following Them?
Neurologist. 2020 Jul;25(4):89-92. doi: 10.1097/NRL.0000000000000281.
5. Chamberlain J, et al. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by
age group (ESETT): a double-blind, responsive-adaptive, randomized controlled trial. Lancet. 2020 Apr
11;395(10231):1217-1224. doi: 10.1016/S0140-6736(20)30611-5.

RATIONALE: □ high risk □ high volume □ high cost X problem prone

Levetiracetam is an antiseizure medication with a mechanism that is not completely understood; however, it is thought
that this medication exerts its antiseizure mechanism by inhibiting voltage-dependent N-type calcium channels which
would later result in modulation of neurotransmitter release1. Levetiracetam is currently approved for the treatment of focal
and generalized onset seizures in both pediatrics and adults. Off label indications include seizure prophylaxis, status
epilepticus, subarachnoid hemorrhage seizure prophylaxis, and traumatic brain injury seizure prophylaxis 1.

The American Epilepsy Society Guidelines has clear recommendations for status epilepticus treatment. First-line
medication therapy includes a benzodiazepine, which is dosed based on the patient’s weight.2 The guidelines define
further that intramuscular midazolam, intravenous lorazepam, or intravenous diazepam should be used first if they are
available.2 If first-line therapy does not result in seizure cessation and seizure duration reaches 20 minutes, the guidelines
endorse using fosphenytoin, valproic acid, or levetiracetam as a second-line agent. The American Epilepsy Society
provides recommendations on loading doses for second-line therapy. Levetiracetam bolus dosing is listed as 60 mg/kg for
one dose with a maximum dose of 4500 mg.2 Previously, the recommended loading dose of levetiracetam was 20 – 40
mg/kg but was changed due to the results of the ESETT trial. This trial compared the efficacy and safety of three
intravenous antiepileptic medications – levetiracetam, fosphenytoin, and valproate.5 ESETT gave patients a levetiracetam
loading dose of 60 mg/kg. They concluded that levetiracetam, fosphenytoin, and valproate were effective in seizure
cessation.5 A study published in 2023 by Braun et al analyzed the impact on patients’ health when comparing appropriate
and inappropriate dosing of benzodiazepines and levetiracetam in status epilepticus. The results showed that only 32% of
patients received the correct loading dose of levetiracetam. 3 For those that received a benzodiazepine, 54.7% of patients
did not receive the recommended dose based on patients’ weight and drug recommendation. This study found that
favorable patient outcomes were more likely for those in the adequate dosing group (63 vs 44 patients, p=0.046).3 They
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seq. All privileges or the immunities of these statutes are claimed.
defined patients as having a favorable outcome as being alive and having a good Glasgow score (> 4). A retrospective
study from 2020 by Parsons et al evaluated dosing of benzodiazepines and second line antiepileptics (fosphenytoin,
levetiracetam, valproic acid, phenobarbital, lacosamide, and topiramate). The results showed that all antiepileptics that
were used were underdosed based on guideline recommended loading doses. The average loading dose of levetiracetam
that was given to a patient was 21.7 mg/kg.4 These retrospective studies demonstrate how guideline recommendations for
status epilepticus loading doses are not consistently followed. Based on the results of these studies showing the
inconsistency with loading doses and how it can negatively affect patient outcomes, it sparked interest to see what
Franciscan Health Indianapolis’s compliance with guideline recommended dosing is.

FINDINGS:
A total of thirty-one patients who received a loading dose of levetiracetam in the emergency department were reviewed.
Patients were selected based on a diagnosis code of seizures, status epilepticus, and convulsions. These patients were
then filtered more and only those who had a seizure witnessed by emergency medical services (EMS) or Franciscan
Health employees were included. This was to ensure the patient experienced a true seizure. If there were multiple
admissions, the first admission was included. Listed below are the findings of this medication use evaluation:
• The average weight for patients receiving levetiracetam was 76.7 kg.
• Fifty-eight percent of patients had a past medical history of seizures. (Figure 1; Table 1)
• The average hospital length of stay was 3.7 days between both groups.
• The average loading dose of Keppra for all thirty-one patients was 33.8 mg/kg. (Figure 2)
• The average loading dose of Keppra for those that did not receive the guideline recommended loading dose was
17.3 mg/kg. (Figure 2)
• Twenty percent of patients had an ICU admission with 67% of those patients not receiving the recommended
levetiracetam loading dose.
• Adverse effects (weakness, behavior abnormalities, somnolence) did not differ between those who received 60
mg/kg loading dose and those who did not.

CONCLUSIONS:
• Ninety percent (28/31) of patients received a benzodiazepine as first-line therapy for seizures. (Figure 3)
• Of those 28 patients that received a benzodiazepine, 15 patients received the guideline recommended dose.
(Figure 4; Table 2)
• Thirty-nine (12/31) percent of patients did not receive guideline recommended loading dose of levetiracetam.
(Figure 5)

Past Medical History of Seizures

PTA Anti-seizure Medications (Table 1)
(Figure 1)
Medication Number of patients (%)
20 Keppra 10 (35%)
Number of Patients

Lamotrigine 4 (14%)
15 18
Oxcarbazepine 3 (10%)
10 58% 13 Lacosamide 2 (7%)
42% Phenobarbital 1 (3%)
5
Zonisamide 2 (7%)
0 None 7 (24%)
Yes No

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seq. All privileges or the immunities of these statutes are claimed.
 Average Keppra Loading Dose (Figure 2)
80

Keppra Loading Dose (mg/kg)

60
60
40

20 33.8
17.3
0

Average dose for all patients

Average dose for those who did NOT receive guideline

recommended dose
Guideline recommended dose

Receipt of benzodiazepine as first- Receipt of correct dose of

line therapy (Figure 3) benzodiazepine (Figure 4)
30

25 28
Number of Patients

20
90%
15 46%
54% 13
10 15
5 10%
3
0

Yes No Yes No

Guideline Recommended Benzodiazepine Dosing (Table 2)

Medication Dose
Intramuscular midazolam >40 kg = 10 mg
13 – 40 kg = 5 mg
Intravenous lorazepam 0.1 mg/kg/dose
Max dose: 4 mg
Intravenous diazepam 0.15 – 0.2 mg/kg/dose
Max dose: 10 mg
Rectal diazepam 0.2 – 0.5 mg/kg
Max dose: 20 mg

This document is protected by the HCQIA 1986, 42 U.S.C. Sec. – 1102, et seq., and by Indiana Peer Review Act, Indiana Code Sec. 34-4-12.6-1, et
seq. All privileges or the immunities of these statutes are claimed.
 Receipt of 60 mg/kg levetiracetam bolus
dose (Figure 5)

39%
12
61%
19

Yes No

SUMMARY
• Roughly one third of patients who presented with a seizure witnessed by EMS personnel or hospital staff were
treated with guideline recommended levetiracetam bolus dosing.
• Nearly half of the patients treated with a benzodiazepine were treated with the correct dose of benzodiazepine.
• Based on the findings stated above, it is recommended that additional education can be given to increase the use
guideline recommended dosing for both benzodiazepine and levetiracetam in the setting of seizures.

ACTION
Action Power of Strategy Person Responsible
(see table below)
Provide education to providers and pharmacists about
the guideline recommendations for levetiracetam 1 Hannah
loading dose.

Error-Reduction Strategy Power (Leverage)

Fail-safes and constraints 10

Forcing Functions 9
Automation and computerization 8
Standardization 6
Redundancies 5
Reminders and checklists 3
Rules and Policies 2
Suggestions to be more careful or
1
vigilant, Education

This document is protected by the HCQIA 1986, 42 U.S.C. Sec. – 1102, et seq., and by Indiana Peer Review Act, Indiana Code Sec. 34-4-12.6-1, et
seq. All privileges or the immunities of these statutes are claimed.