Levetiracetam‐associated behavioral adverse events in neurocritical care patients

Strein, Micheal; Holton-Burke, John; Stilianoudakis, Spiro; Moses, Carley; Almohaish, Sulaiman; Brophy, Gretchen M.

doi:10.1002/phar.2760

Cited by 7 publications

(4 citation statements)

References 33 publications

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“…Additionally, prescribers may have overestimated the potential risks associated with higher doses. Although LEV is generally well tolerated (11, 22), behavioral abnormalities (agitation, delirium, anxiety) have been reported in up to 46% of patients, although it is unclear if these events represent a drug side effect or are related to the primary brain injury (23). To this point, the PEACH trial found no difference in serious adverse events, depression, or anxiety in patients who received LEV 500 twice daily compared to placebo (6).…”

Section: Discussionmentioning

confidence: 99%

Optimal Dosing of Levetiracetam for Seizure Prophylaxis in Critically Ill Patients: A Prospective Observational Study

Valdes,

Fang,

Boffa

et al. 2023

Critical Care Medicine

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Objectives: Critically ill patients eliminate levetiracetam (LEV) more rapidly than healthy controls, yet low doses are commonly used for seizure prophylaxis in the ICU setting. We compared the rates of achievement of target serum levels and new onset seizure (clinical and/or electrographic) among patients who received low (500 mg bid) versus high (750–1,000 ;mg bid) dose LEV. Design: Prospective, observational study. Setting: Tertiary care, academic center. Patients: We included patients who received prophylactic LEV following traumatic brain injury, intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, or supratentorial neurosurgery between 2019 and 2021. Patients with a history of seizure, antiseizure medication use, or renal failure requiring dialysis were excluded. Interventions: None. Measurements: LEV levels were obtained at steady state. The impact of low-dose versus high-dose LEV on the primary outcome of target LEV levels (12–46 μg/mL), and the secondary outcome of clinical and/or electrographic seizure, were assessed using multivariable logistic regression analyses adjusting for age, LEV loading dose, BMI, primary diagnosis and creatinine clearance (CrCl). Main Results: Of the 205 subjects included in analyses, n = 106 (52%) received LEV 500 mg bid (median 13 mg/kg/d), and n = 99 (48%) received LEV 750–1,000 mg bid (median 25 mg/kg/d). Overall, 111 of 205 patients (54%) achieved target levels: 48 (45%) from the low-dose group versus 63 (64%) from the high-dose group (odds ratio [OR] 2.1; 95% CI, 1.1–3.7; p = 0.009). In multivariable analyses, high-dose LEV predicted target levels (adjusted OR [aOR] 2.23; 95% CI, 1.16–4.27; p = 0.016), and was associated with lower seizure odds (aOR 0.32; 95% CI, 0.13–0.82; p = 0.018) after adjusting for age, loading dose, BMI, diagnosis, and CrCl. Conclusions: Underdosing of LEV was common, with only 54% of patients achieving target serum levels. Higher doses (750–1,000 mg bid) were more than twice as likely to lead to optimal drug levels and reduced the odds of seizure by 68% compared with low-dose regimens (500 mg bid).

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Section: Discussionmentioning

confidence: 99%

Optimal Dosing of Levetiracetam for Seizure Prophylaxis in Critically Ill Patients: A Prospective Observational Study

Valdes,

Fang,

Boffa

et al. 2023

Critical Care Medicine

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“…As levetiracetam is associated with behavioral adverse reactions, possibly due to its potential inhibitory effects on the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, brivaracetam has attracted attention because it may have fewer behavioral side effects given that it does not appear to work via this mechanism. 26 However, there is less evidence supporting its use in treating SE. The dosing for brivaracetam for SE is not well defined, but a loading dose of 200 mg followed by maintenance doses of 50 to 100 mg twice daily is considered reasonable at this urgent treatment stage.…”

Section: Updates On Benzodiazepinesmentioning

confidence: 99%

“…Antiseizure medications and dosing in status epilepticus5,6,26,[29][30][31][32][33][34][35][36][37][38]61 26. However, there is less evidence supporting its use in treating SE.…”

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confidence: 99%

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Status Epilepticus: An Update on Pharmacological Management

Almohaish,

Tesoro,

Brophy

2024

Semin Neurol

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Status epilepticus (SE) is a neurological emergency that requires timely pharmacological therapy to cease seizure activity. The treatment approach varies based on the time and the treatment stage of SE. Benzodiazepines are considered the first-line therapy during the emergent treatment phase of SE. Antiseizure medicines such as phenytoin, valproic acid, and levetiracetam are recommended during the urgent treatment phase. These drugs appear to have a similar safety and efficacy profile, and individualized therapy should be chosen based on patient characteristics. Midazolam, propofol, pentobarbital, and ketamine are continuous intravenous infusions of anesthetic medications utilized in the refractory SE (RSE) period. The most efficacious pharmacotherapeutic treatments for RSE and superrefractory status epilepticus are not clearly defined.

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