Therapeutic Drug Monitoring of Levetiracetam in Select Populations

Jarvie, Dael; Mahmoud, Sherif Hanafy

doi:10.18433/jpps30081

Cited by 39 publications

(26 citation statements)

References 38 publications

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“…Headache was the second most common side effect reported in this study. Other studies have found that the similar observation [15]. Finally, with regard to whether participants believed Levetiracetam could harm or kill, majority of them were aware about the toxicity of Levetiracetam.…”

Section: Discussionsupporting

confidence: 66%

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Levetiracetam Use, Availability and Knowledge of Toxicity Among Epileptic Patients and Their Care Givers: A Cross-Sectional Study in King Salman Armed Forces Hospital Tabuk Saudi Arabia

Alatawi

Alzahrani

Saiyed

2021

ijsr

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Background: Levetiracetam (Keppra®) is a well-known second-generation anti-epileptic drug (AED). The study was aimed to addresses Levetiracetam use, availability and knowledge of toxicity among epileptic patients and their care givers in King Salman Armed Forces Hospital Tabuk Saudi Arabia. Methods: This cross-sectional survey was conducted in King Salman Armed Forces Hospital (KSAFH) in Tabuk city in Saudi Arabia. The study participants were epileptic patients and their care givers, selected from different outpatient departments using a convenient sampling technique. Data was collected using an Arabic self-reported questionnaire consisted of open-ended and closed-ended questions to facilitate study participants. Altogether, 381 persons answered the full questionnaire. The data were entered into SPSS version 26.0 for Windows, cleaned and managed before analysis. Results: Participants age ranged from 18 to 63 years, with a mean 29.6 years and standard deviation 5.8 years. 47.0% (n= 179) were male and 53.0% (n= 202) female. Six out of ten participants lived in the urban area (67.7%). Majority of the participants had knowledge about seizures (96.9%). About 31.0% of the participants and/or patients had seizures (epilepsy) since more than 20 years. Nearly 28.0% participants and/or patients had family history of seizures (epilepsy). Majority of the participants had Levetiracetam at home and aware of the correct usage of it. However, about 11% of the participants felt that Levetiracetam is used to help sleep. Eight out of ten of the participants reported “Sleepiness” as the side effect of Levetiracetam (79.3%). Half of the participants reported “Headache” as the side effect of Levetiracetam. About 94.0% of the participants knew that someone could take enough Levetiracetam to harm themselves. Conclusion: The study population used Levetiracetam, they demonstrated basic awareness of Levetiracetam use including the potential consequences of overdosing. Participants' knowledge regarding the toxicity of Levetiracetam is adequate. Special awareness programs for parents of children with epilepsy may be needed to reduce the knowledge gaps in the management of epilepsy and to ensure compliance and optimal therapeutic outcomes.

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Section: Discussionsupporting

confidence: 66%

“…Levetiracetam is a broad-spectrum antiepileptic drug with a unique mechanism of action. AEDs are strong agents that can cause numerous adverse reactions and drug-drug interactions [13][14][15]. This survey is aimed to determine the usage, availability and knowledge of toxicity of Levetiracetam among the patients.…”

Section: Discussionmentioning

confidence: 99%

Levetiracetam Use, Availability and Knowledge of Toxicity Among Epileptic Patients and Their Care Givers: A Cross-Sectional Study in King Salman Armed Forces Hospital Tabuk Saudi Arabia

Alatawi

Alzahrani

Saiyed

2021

ijsr

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“…LEV exhibits first-order kinetics following a single dose and during long-term administration with excretion primarily through kidneys [ 4 ]. Half-life of LEV is 6–8 h in healthy adults, reaching steady states within 48 h [ 4 , 5 , 6 , 7 ]. Metabolism of LEV is not dependent on the hepatic cytochrome P450 system, whereas the acetamide group of plasma hydroxylase is involved [ 2 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…In children with epilepsy, the half-life of LEV was shorter and clearance rates were higher than those in adults [ 17 ]. On the contrary, the half-life was longer and clearance rates were lower in elderly patients, compared to those in young adults and children [ 5 , 18 ]. In patients with renal impairment, LEV clearance was decreased in all ages [ 5 , 16 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

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Levetiracetam Therapeutic Drug Monitoring in a Large Cohort of Korean Epileptic Patients

Lee

Joo

et al. 2021

Pharmaceuticals

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Levetiracetam is a new antiepileptic drug (AED) used for treating and preventing partial or generalized seizures. The usefulness of levetiracetam therapeutic drug monitoring (TDM) is related to inter- or intra-individual pharmacokinetic variability, drug interactions, and patient noncompliance. We aimed to investigate the levetiracetam TDM status in Korean epilepsy patients. Serum trough levetiracetam concentrations were measured using liquid chromatography–tandem mass spectrometry in 710 samples from 550 patients. The median (range) daily and weight-adjusted levetiracetam doses were 1500 (20–5000) mg and 25.5 (3.03–133.0) mg/kg, respectively. Patients on levetiracetam monotherapy constituted only 19.5% of the population, while 30.1% were on co-medication with valproate and 56.0% with enzyme-inducing AEDs (EIAEDs). Observed levetiracetam concentrations were widely distributed, ranging 0.8–95 mg/L, with a median of 17.3 mg/L. Levetiracetam concentrations were therapeutic, supra-therapeutic, and sub-therapeutic in 58.5% (n = 393), 11.6% (n = 78), and 29.9% (n = 201) of samples, respectively. There was a strong correlation between weight-adjusted levetiracetam dosage and concentrations (ρ = 0.6896, p < 0.0001). In this large-scale clinical study, a large inter-individual difference in levetiracetam pharmacokinetics was observed, and levetiracetam concentrations were influenced by EIAEDs. For individual dose adjustments and monitoring compliance, routine levetiracetam TDM is needed in epilepsy patients.

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Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations

Shen

Shao

Wang

et al. 2023

CPT Pharmacom & Syst Pharma

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Levetiracetam (LEV) is an anti-epileptic drug approved for use in various populations. The pharmacokinetic (PK) behavior of LEV may be altered in the elderly and patients with renal and hepatic impairment. Thus, dosage adjustment is required. This study was conducted to investigate how the physiologically-based PK (PBPK) model describes the PKs of LEV in adult and elderly populations, as well as to predict the PKs of LEV in patients with renal and hepatic impairment in both populations. The whole-body PBPK models were developed using the reported physicochemical properties of LEV and clinical data. The models were validated using data from clinical studies with different dose ranges and different routes and intervals of administration. The fit performance of the models was assessed by comparing predicted and observed blood concentration data and PK parameters. It is recommended that the doses be reduced to ~70%, 60%, and 45% of the adult dose for the mild, moderate, and severe renal impairment populations and ~95%, 80%, and 57% of the adult dose for the Child Pugh-A (CP-A), Child Pugh-B (CP-B), and Child Pugh-C (CP-C) hepatic impairment populations, respectively. No dose adjustment is required for the healthy elderly population, but dose reduction is required for the elderly with organ dysfunction accordingly, on a scale similar to that of adults. A PBPK model of LEV was successfully developed to optimize dosing regimens for special populations. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?The role of multiple physiological factors contributing to the large variability in levetiracetam (LEV) pharmacokinetics (PKs) has not been systematically characterized, and the functional status of the major drug elimination organs may influence the behavior of LEV exposure in vivo, which may confound information

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Therapeutic Drug Monitoring of Levetiracetam in Select Populations

Abstract: Routine TDM of levetiracetam is not recommended for all populations, however, it may be beneficial to maintain an individual therapeutic range in patients where the PK of LEV may be altered, such as in patients who are critically ill patients, pregnant, pediatrics or elderly.

Cited by 39 publications

References 38 publications

Levetiracetam Use, Availability and Knowledge of Toxicity Among Epileptic Patients and Their Care Givers: A Cross-Sectional Study in King Salman Armed Forces Hospital Tabuk Saudi Arabia

Levetiracetam Use, Availability and Knowledge of Toxicity Among Epileptic Patients and Their Care Givers: A Cross-Sectional Study in King Salman Armed Forces Hospital Tabuk Saudi Arabia

Levetiracetam Therapeutic Drug Monitoring in a Large Cohort of Korean Epileptic Patients

Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations

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